Surgeons
22 years of experience
Video profile
Accepting new patients
Woods Corner
Lahey Clinic
41 Mall Rd
Burlington, MA 01803
781-744-8971
Locations and availability (3)

Education ?

Medical School Score Rankings
University of California at San Francisco (1988)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Awards  
Castle Connolly America's Top Doctors® (2010 - 2014)
Castle Connolly America's Top Doctors® for Cancer (2007, 2009 - 2012, 2014)
Patients' Choice 5th Anniversary Award (2012 - 2013)
Patients' Choice Award (2008 - 2013)
Compassionate Doctor Recognition (2013)
Associations
American Board of Colon and Rectal Surgery
American Board of Surgery

Affiliations ?

Dr. Read is affiliated with 7 hospitals.

Hospital Affilations

Score

Rankings

  • Allegheny General Hospital
    320 E North Ave, Pittsburgh, PA 15212
    • Currently 4 of 4 crosses
    Top 25%
  • Lahey Clinic *
    41 Mall Rd, Burlington, MA 01803
    • Currently 3 of 4 crosses
    Top 50%
  • Western Pennsylvania Hospital
    4800 Friendship Ave, Pittsburgh, PA 15224
    • Currently 3 of 4 crosses
    Top 50%
  • Lahey Clinic Hospital,Inc
  • West Penn Allegheny Health System
  • Western Pennsylvania Hospital-Forbes Regional Camp
  • Barnes Jewish Hospital
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Read has contributed to 50 publications.
    Title Urinary Tract Infection After Colon and Rectal Resections: More Common Than Predicted by Risk-adjustment Models.
    Date January 2012
    Journal Journal of the American College of Surgeons
    Excerpt

    Urinary tract infections (UTIs) are the most common hospital-acquired infections in the United States. We hypothesized that the risk of UTI after colorectal surgery exceeds the risk after other gastrointestinal operations.

    Title Perforation After Stenting of Obstructing Sigmoid Cancer Caused by Acute Angulation of the Colon.
    Date November 2011
    Journal The American Surgeon
    Title Laparoscopic Colectomy Using Cancer Principles is Appropriate for Colonoscopically Unresectable Adenomas of the Colon.
    Date July 2010
    Journal Diseases of the Colon and Rectum
    Excerpt

    This study was undertaken to determine the risks of cancer in unresectable polyps and to compare the short-term outcome of laparoscopic colectomy with that of open colectomy for benign polyps.

    Title Colectomy for Fulminant Clostridium Difficile Colitis: Predictors of Mortality.
    Date June 2010
    Journal The American Surgeon
    Excerpt

    The purpose of this study was to define clinical and radiographic variables associated with postoperative mortality after urgent colectomy for fulminant Clostridium difficile colitis. Data were obtained regarding patients undergoing colectomy for fulminant C. difficile colitis at two institutions (1997-2005). Univariate analysis of factors predicting 30-day mortality was performed using chi2 and Student's t tests. Multivariable logistic regression was done to include all variables whose P value was < 0.20. Clinical variables analyzed included: age, gender, recent operation, comorbidities, preoperative multisystem organ failure, vasopressors, symptom duration, time to surgery, serum albumin, change in serum albumin, serum creatinine, white blood cell count, and extent of colectomy. Computed tomography variables included: ascites, megacolon, and extent of colitis. Thirty-five patients (mean age 70 years, 46% male) underwent urgent colectomy for C. difficile colitis. The 30-day mortality rate was 45.7 per cent (16/35). The only clinical variable associated with mortality was preoperative multisystem organ failure (nonsurvivors 9/16 vs survivors: 4/19; P = 0.037). None of the three patients undergoing partial colectomy survived, although the difference in survival versus those undergoing subtotal colectomy was not significant. Patients with fulminant C. difficile colitis undergoing colectomy have a high mortality rate. Preoperative presence of multisystem organ failure was independently predictive of mortality.

    Title Variability in Reconstructive Procedures Following Rectal Cancer Surgery in the United States.
    Date June 2010
    Journal Diseases of the Colon and Rectum
    Excerpt

    We sought to identify variability in surgical care for rectal cancer across the United States. In particular, we hypothesized that in large areas of the country patients are infrequently treated by proctectomy using restorative ("sphincter-sparing") techniques.

    Title Surgeon Involvement in the Care of Patients Deemed to Have "preventable" Conditions.
    Date January 2010
    Journal Journal of the American College of Surgeons
    Excerpt

    As of October 1, 2008, the Centers for Medicare and Medicaid Services stopped payment for 8 "preventable" conditions: retained foreign body, air embolism, blood incompatibility, catheter-associated urinary tract infection, pressure ulcer, vascular catheter-associated infection, mediastinitis, and hospital fall. Our hypothesis was that surgeons are frequently involved in the care of patients deemed to have "preventable" conditions.

    Title Anastomotic Leak Testing After Colorectal Resection: What Are the Data?
    Date June 2009
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    To determine the value of anastomotic leak testing of left-sided colorectal anastomoses.

    Title Laparoscopic Vs. Open Total Abdominal Colectomy for Severe Colitis: Impact on Recovery and Subsequent Completion Restorative Proctectomy.
    Date April 2009
    Journal Diseases of the Colon and Rectum
    Excerpt

    This study was designed to compare short-term outcomes of laparoscopic vs. open total abdominal colectomy and end ileostomy for severe ulcerative colitis and to evaluate the impact of the initial surgical approach on subsequent operations for three-stage restorative proctocolectomy.

    Title Hand-assisted Laparoscopic Vs. Laparoscopic Colorectal Surgery: a Multicenter, Prospective, Randomized Trial.
    Date June 2008
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: This study was designed to compare short-term outcomes after hand-assisted laparoscopic vs. straight laparoscopic colorectal surgery. METHODS: Eleven surgeons at five centers participated in a prospective, randomized trial of patients undergoing elective laparoscopic sigmoid/left colectomy and total colectomy. The study was powered to detect a 30-minute reduction in operative time between hand-assisted laparoscopic and straight laparoscopic groups. RESULTS: There were 47 hand-assisted patients (33 sigmoid/left colectomy, 14 total colectomy) and 48 straight laparoscopic patients (33 sigmoid/left colectomy, 15 total colectomy). There were no differences in the patient age, sex, body mass index, previous surgery, diagnosis, and procedures performed between the hand-assisted and straight laparoscopic groups. Resident participation in the procedures was similar for all groups. The mean operative time (in minutes) was significantly less in the hand-assisted laparoscopic group for both the sigmoid colectomy (175 +/- 58 vs. 208 +/- 55; P = 0.021) and total colectomy groups (time to colectomy completion, 127 +/- 31 vs. 184 +/- 72; P = 0.015). There were no apparent differences in the time to return of bowel function, tolerance of diet, length of stay, postoperative pain scores, or narcotic usage between the hand-assisted laparoscopic and straight laparoscopic groups. There was one (2 percent) conversion in the hand-assisted laparoscopic group and six (12.5 percent) in the straight laparoscopic group (P = 0.11). Complications were similar in both groups (hand-assisted, 21 percent vs. straight laparoscopic, 19 percent; P = 0.68). CONCLUSIONS: In this prospective, randomized study, hand-assisted laparoscopic colorectal surgery resulted in significantly shorter operative times while maintaining similar clinical outcomes as straight laparoscopic techniques for patients undergoing left-sided colectomy and total abdominal colectomy.

    Title Laparoscopic Colectomy for Apparently Benign Colorectal Neoplasia: A Word of Caution.
    Date March 2008
    Journal Surgical Endoscopy
    Excerpt

    PURPOSE: Endoscopically unresectable apparently benign colorectal polyps are considered by some surgeons as ideal for their early laparoscopic colectomy experience. Our hypotheses were: (1) a substantial fraction of patients undergoing laparoscopic colectomy for apparently benign colorectal neoplasia will have adenocarcinoma on final pathology; and (2) in our practice, we perform an adequate laparoscopic oncological resection for apparently benign polyps as evidenced by margin status and nodal retrieval. METHODS: Data from a consecutive series of patients undergoing laparoscopic colectomy (on an intention-to-treat basis) for endoscopically unresectable neoplasms with benign preoperative histology were retrieved from a prospective database and supplemented by chart review. RESULTS: The study population consisted of 63 patients (mean age 67, mean body mass index 29). Two out of 63 cases (3%) were converted to laparotomy because of extensive adhesions (n = 1) and equipment failure (n = 1). Colectomy type: right/transverse (n = 49, 78%); left/anterior resection (n = 10, 16%); subtotal (n = 4, 6%). Invasive adenocarcinoma was found on histological analysis of the colectomy specimen in 14 out of 63 cases (22%), standard error of the proportion 0.052. Staging of the 14 cancers were I (n = 6, 43%), II (n = 3, 21%), III ( = 4, 29%), and IV (n = 1, 7%). The median nodal harvest was 12 and all resection margins were free of neoplasm. Neither dysplasia on endoscopic biopsy nor lesion diameter was predictive of adenocarcinoma. Eight out of 23 (35%) patients with dysplasia on endoscopic biopsy had adenocarcinoma on final pathology versus 6/40 (15%) with no dysplasia (p = 0.114, Fisher's exact test). Mean diameter of benign tumors was 3.2 cm (range 0.5-10.0cm) versus 3.9cm (range 1.5-7.5cm) for adenocarcinomas (p = 0.189, t - test). CONCLUSION: A substantial fraction of endoscopically unresectable colorectal neoplasms with benign histology on initial biopsy will harbor invasive adenocarcinoma, some of advanced stage. This finding supports the practice of performing oncological resection for all patients with endoscopically unresectable neoplasms of the colorectum. The inexperienced laparoscopic colectomist should approach these cases with caution.

    Title Occult Perineal Endometrioma Diagnosed by Endoanal Ultrasound and Treated by Excision: a Report of 3 Cases.
    Date December 2007
    Journal The Journal of Reproductive Medicine
    Excerpt

    BACKGROUND: Isolated perineal endometrioma is a rare entity and often causes diagnostic uncertainty. CASES: Three premenopausal women, none with a prior history of endometriosis, presented with vague perineal pain 3-6 months following obstetric delivery with episiotomy. The latency periods between the onset of symptoms and definitive diagnosis were 3 months, 18 months and 3 years despite multiple physician evaluations in the interim. Patient presentation and management were virtually identical in all cases. Detailed questioning revealed that the pain was located adjacent to the episiotomy incision and waxed and waned with menses. Physical examination revealed a vague fullness adjacent to the episiotomy incision. Endoanal ultrasound revealed a mass of mixed echogenicity adjacent to the external anal sphincter. Transperineal exploration revealed a tumor with the gross appearance of an endometrioma, which was confirmed histologically. Excision of the mass with preservation of the anal sphincter muscle resulted in resolution of symptoms in all patients without the need for hormonal manipulation. No patient suffered diminution of fecal continence. CONCLUSION: Occult perineal endometriosis should be considered when a woman presents with cyclic pain in the perineum following delivery and episiotomy. Endoanal ultrasound can assist with the diagnosis. Transperineal excision with sparing of the anal sphincter can be curative, without compromising continence.

    Title Laparoscopic Rectal Surgery: Rectal Cancer, Pelvic Pouch Surgery, and Rectal Prolapse.
    Date October 2006
    Journal The Surgical Clinics of North America
    Excerpt

    With the increasing popularity of minimally invasive approaches to surgery, laparoscopic techniques are being applied increasingly to more complex procedures. Surgeons who are interested in gaining skill and confidence with the techniques of rectal mobilization and resection initially should consider attempting procedures for benign disease. Patients who have rectal prolapse, who often have wide, accommodating pelvic anatomy, are the logical choice with whom to begin the laparoscopic rectal experience. Laparoscopic restorative proctocolectomy is more technically challenging. Laparoscopic proctectomy for rectal cancer probably should remain in the hands of well-trained, high-volume, experienced surgeons who have built a dedicated team for treatment of these patients, and who track their outcomes prospectively.

    Title Ileal Perforation Secondary to Clostridium Difficile Enteritis: Report of 2 Cases.
    Date February 2006
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    Two cases of small-bowel perforation secondary to Clostridium difficile enteritis are described and compared with the 8 cases of C difficile enteritis reported in the medical literature. The cause of small-bowel involvement with C difficile is unknown, but prior antibiotic use, prior colectomy, chronic alterations in small-bowel flora, and other host factors are discussed.

    Title Delayed Treatment for Rectal Cancer.
    Date October 2005
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: Reports of the relationship between length of delay before diagnosis of rectal cancer and stage of the disease have been mixed. The present study documented the magnitude and medical ramifications of delay in diagnosing rectal cancer. METHODS: One hundred twenty patients who had been recently diagnosed with rectal cancer provided information regarding history of symptoms and initial perceptions of those symptoms. Patients also estimated the time elapsed from onset of symptoms until their first consultation with a physician, as well as time elapsed from consultation until the diagnosis of rectal cancer was made. Stage information was gathered from patient charts. RESULTS: For 106 of the patients, the first sign of rectal cancer was in the form of symptoms, and the most common first symptom was rectal bleeding. For the remaining 14 patients, their cancer was first discovered through routine examination. Over 75 percent of patients with symptoms did not initially believe that they were caused by cancer or any other serious problem, and over 50 percent attributed their symptoms to hemorrhoids. There was a clear trend, albeit statistically nonsignificant, toward worsening disease with longer delays. Median delay times in weeks were Stage I (10.0 weeks), Stage II (14.0 weeks), Stage III (18.5 weeks), and Stage IV (26.0 weeks). CONCLUSIONS: Delayed diagnosis for rectal cancer remains a significant problem, with instances of delay attributable to both patient and physician. Delayed diagnosis can result in more serious disease and, when attributable to the physician, can result in damaged trust and sometimes legal action.

    Title Sentinel Lymph Node Mapping for Adenocarcinoma of the Colon Does Not Improve Staging Accuracy.
    Date February 2005
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: This study was designed to: determine the efficacy of sentinel lymph node mapping in patients with intraperitoneal colon cancer; and create an algorithm to predict potential survival benefit by using best-case estimates in favor of sentinel node mapping and lymph node ultraprocessing techniques. METHODS: Forty-one patients with intraperitoneal colon cancer undergoing colectomy with curative intent were studied prospectively. After mobilization of the colon and mesentery, 1 to 2 ml of isosulfan blue dye was injected subserosally around the tumor. The first several nodes highlighted with blue dye were identified as sentinel nodes. Additional nodes were identified by the pathologist in routine fashion by manual dissection of the mesentery. All nodes were processed in routine fashion by bivalving and hematoxylin and eosin staining. To create an algorithm to predict potential survival benefit of sentinel node mapping and lymph node ultraprocessing techniques, assumptions were made using data from the literature. All bias was directed toward success of the techniques. RESULTS: Three of 41 patients (7 percent) did not undergo injection of dye and were excluded from further analysis. Stage of disease in the remaining 38 patients was: I, n = 10 (26 percent); II, n = 15 (39 percent); III, n = 11 (29 percent); IV, n = 2 (5 percent). At least one sentinel node was identified in 30 of 38 patients (79 percent). The median number of sentinel nodes identified was two (range, 1-3). Median total nodal retrieval was 14 (range, 7-45). All nodes were negative in 26 of 38 patients (68 percent). Sentinel nodes and nonsentinel nodes were positive in 2 of 38 patients (5 percent). Sentinel nodes were the only positive nodes in 1 of 38 patients (3 percent). Sentinel nodes were negative and nonsentinel nodes were positive in 9 of 38 patients (24 percent). Thus, sentinel node mapping would have potentially benefited only 3 percent, and failed to accurately identify nodal metastases in 24 percent of the patients in our study. To create a survival benefit algorithm, we assumed the following: combined fraction of Stage I and II disease (0.5); fraction understaged by bivalving and hematoxylin and eosin staining that would have occult positive nodes by more sophisticated analysis (0.15); fraction of occult positive nodes detected by sentinel node mapping (0.9); and survival benefit from chemotherapy (0.33). Thus, the fraction of patients benefiting from sentinel lymph node mapping and lymph node ultraprocessing techniques would be 0.02 (2 percent). CONCLUSIONS: Sentinel node mapping with isosulfan blue dye and routine processing of retrieved nodes does not improve staging accuracy in patients with intraperitoneal colon cancer. Even using best-case assumptions, the percentage of patients who would potentially benefit from sentinel lymph node mapping is small.

    Title Neoadjuvant Therapy for Rectal Cancer: Histologic Response of the Primary Tumor Predicts Nodal Status.
    Date July 2004
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: This study was designed to compare histologic T and N stages in patients with rectal adenocarcinoma undergoing various neoadjuvant radiotherapy regimens and proctectomy, in an attempt to determine if final histologic stage of the mural tumor predicts nodal status. METHODS: Data were collected from computerized databases at two institutions on 649 consecutive patients who underwent neoadjuvant radiotherapy or chemoradiotherapy and proctectomy for primary adenocarcinoma of the rectum from 1990 to 2002. RESULTS: Five patients were excluded because of incomplete pathology data sets, leaving a study population of 644. Patients underwent neoadjuvant radiotherapy alone (2000 cGy in 5 fractions, n = 191; or 4500 cGy in 25 fractions, n = 259) or chemoradiation (4500 cGy in 25 fractions with concurrent 5-fluorouracil, n = 194). Histologic stage of the remaining mural tumor (ypT) correlated with nodal status (ypN). Lymph nodes harboring metastatic tumor were found in 1 of 42 (2 percent) ypT0 patients, 2 of 45 (4 percent) ypT1 patients, 43 of 186 (23 percent) ypT2 patients, 158 of 338 (47 percent) ypT3 patients, and 16 of 33 (48 percent) ypT4 patients ( P < 0.001, chi-squared test). The probability of finding ypN+ disease was 3 of 87 (3 percent) in patients with ypT0-1 residual primary tumors vs. 220 of 557 (39 percent) in patients with ypT2-4 residual primary tumors ( P < 0.0001; Fisher's exact test). CONCLUSIONS: Nodal metastases are rare in patients whose mural tumor burden shrinks to ypT0-1 after neoadjuvant radiotherapy. If transanal excision is offered to select patients with distal rectal cancer, it is reasonable to select those who have an excellent clinical response to neoadjuvant therapy for transanal excision, and then reserve proctectomy for patients proven to have residual ypT2-4 disease.

    Title The Addition of Continuous Infusion 5-fu to Preoperative Radiation Therapy Increases Tumor Response, Leading to Increased Sphincter Preservation in Locally Advanced Rectal Cancer.
    Date October 2003
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences. PATIENTS AND METHODS: Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m(2)/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS). RESULTS: Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors < or /=6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2. CONCLUSIONS: The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.

    Title Supplemental Perioperative Fluid Administration Increases Tissue Oxygen Pressure.
    Date March 2003
    Journal Surgery
    Excerpt

    BACKGROUND: Wound infections are common and serious surgical complications. Wound perfusion delivers oxygen, inflammatory cells, growth factors, and cytokines to injured tissues. Hypoperfused regions experience low oxygen tensions that do not support adequate oxidative killing or wound healing. Clinicians may fail to recognize clinically important hypovolemia because hemodynamic stability and urine output are maintained after peripheral perfusion is compromised. We tested the hypothesis that supplemental fluid administration during and after elective colon resection increases tissue perfusion and tissue oxygen pressure. METHODS: Fifty-six patients undergoing colon resection were randomly assigned to conservative (8 mL x kg(-1) x h(-1), n = 26) or aggressive (16 to 18 mL x kg(-1) x h(-1), n = 30) fluid management. Anesthetic technique was standardized. We used 60% nitrous oxide in 40% oxygen. During surgery and postanesthetic recovery, subcutaneous oxygen tension (P(sq)O(2)) was measured by using a polarographic sensor implanted subcutaneously into 1 upper arm. Capillary blood flow was evaluated postoperatively with a thermal diffusion system. Data were analyzed with 2-tailed t tests; P value less than.05 was considered statistically significant. RESULTS: Hemodynamic and renal responses were similar in the groups. Intraoperative tissue oxygen tension was significantly greater in patients given supplemental fluid: 81 +/- 26 vs 67 +/- 18 mm Hg, P =.03. Postoperative P(sq)O(2) (77 +/- 26 vs 59 +/- 15 mm Hg, P =.009) and capillary blood flow (69 +/- 12 vs 53 +/- 12, P <.001) were also greater in the supplemental fluid patients. CONCLUSIONS: Supplemental perioperative fluid administration significantly increases tissue perfusion and tissue oxygen partial pressure. Optimizing tissue perfusion will require providing more fluid than indicated by normal clinical criteria or use of invasive monitoring to guide treatment. The actual effect of supplemental fluid administration on incidence of wound infection requires further investigation.

    Title Prospective Evaluation of Anesthetic Technique for Anorectal Surgery.
    Date January 2003
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: Deep intravenous sedation plus local anesthesia for anorectal surgery in the prone position is used frequently at our institution, but is not widely accepted because of concerns regarding airway management. The purpose of this study was to prospectively evaluate the safety and efficacy of this anesthetic technique for anorectal surgery. METHODS: Data were collected prospectively on 413 consecutive patients (mean age, 47 years; mean weight, 80 kg) undergoing anorectal surgical procedures. RESULTS: Of the 389 patients who underwent anorectal procedures in the prone position, 260 (67 percent) received intravenous sedation plus local anesthesia, 125 (32 percent) received regional anesthesia (spinal or epidural), and 4 (1 percent) received general endotracheal anesthesia. Of the 24 patients who underwent anorectal procedures in the lithotomy position, 13 (54 percent) received intravenous sedation plus local anesthesia, 2 (8 percent) received regional anesthesia, 2 (8 percent) received general endotracheal anesthesia, and 7 (29 percent) received mask inhalational anesthesia. Forty-two adverse events attributable to the anesthetic occurred in 18 patients: nausea and vomiting (n = 17), transient hypotension, bradycardia, or arrhythmia (n = 8), transient hypoxia or hypoventilation (n = 7), urinary retention (n = 6), and severe patient discomfort (n = 2). These complications occurred in 4 percent (10/273) of patients receiving intravenous sedation plus local anesthesia and in 6 percent (8/127) of patients receiving regional anesthesia. Two of 260 patients (0.8 percent) receiving intravenous sedation plus local anesthesia in the prone position were rolled supine before completing the surgical procedure. Recovery time before discharge for patients treated on an ambulatory basis was significantly shorter for those patients undergoing intravenous sedation plus local anesthesia (79 +/- 34 minutes, n = 174) than for patients undergoing regional anesthesia (161 +/- 63 minutes, n = 45; P < 0.001, t-test). CONCLUSION: Intravenous sedation plus local anesthesia in the prone position is safe and effective for anorectal surgery and offers potential cost savings by decreasing recovery room time for outpatient procedures.

    Title Surgeon Specialty is Associated with Outcome in Rectal Cancer Treatment.
    Date August 2002
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: The aim of this study was to determine the effect of surgeon specialty on disease-free survival and local control in patients with adenocarcinoma of the rectum. Patients underwent curative treatment with neoadjuvant external beam radiotherapy and proctectomy by colorectal surgeons and noncolorectal surgeons. METHODS: The records of 384 consecutive patients treated by colorectal surgeons (n = 251) and noncolorectal surgeons (n = 133) from 1977 to 1995 were reviewed independently by physicians in the Division of Radiation Oncology. Local recurrence was defined as pelvic recurrence occurring in the presence or absence of distant metastatic disease. RESULTS: The study population comprised 213 males, mean age 64 (range, 19-97) years. Preoperative radiotherapy was delivered as 4,500 cGy in 25 fractions six to eight weeks before surgery (n = 293) or 2,000 cGy in 5 fractions immediately before surgery (n = 91). Concurrent preoperative chemotherapy was given to 14 patients, postoperative chemotherapy to 55. Overall actuarial disease-free survival and local control rates were 74 and 90 percent, respectively, at five years. Actuarial disease-free survival and local control rates at five years were 77 and 93 percent for colorectal surgeons vs. 68 and 84 percent for noncolorectal surgeons (P < or = 0.005 for both, Tarone-Ware). Multivariate analysis revealed that pathologic stage and background of the surgeon were the only independent predictors of disease-free survival (both P < or = 0.006, Cox proportional hazards) and that pathologic stage, background of the surgeon, and proximal location of the tumor were independent predictors of local control (all P < or = 0.02, Cox proportional hazards). Radiation dose and use of chemotherapy were not significant factors. Sphincter preservation was more common by colorectal surgeons (131/251, 52 percent) than noncolorectal surgeons (40/133, 30 percent; P = 0.00004, Fisher's exact test, two-tailed). CONCLUSION: Good outcome for patients with adenocarcinoma of the rectum who undergo neoadjuvant external beam radiotherapy and proctectomy is associated with subspecialty training in colon and rectal surgery.

    Title Locoregional Recurrence and Survival After Curative Resection of Adenocarcinoma of the Colon.
    Date July 2002
    Journal Journal of the American College of Surgeons
    Excerpt

    BACKGROUND: There is wide variability in reported locoregional recurrence rates after curative resection of adenocarcinoma of the intraperitoneal colon, and there is no universally accepted surgical technique regarding length of the resected specimen or extent of lymphadenectomy. The aim of this study was to determine the disease-free survival, locoregional failure, and perioperative morbidity of patients undergoing curative resection of colon adenocarcinoma. STUDY DESIGN: The records of 316 consecutive patients undergoing curative resection for primary adenocarcinoma of the intraperitoneal colon between 1990 and 1995 were reviewed. Locoregional recurrence was defined as disease at the anastomosis or in the adjacent mesentery, peritoneum, retroperitoneum, or carcinomatosis. The product-limit method (Kaplan-Meier) was used to analyze survival and tumor recurrence. RESULTS: The study population comprised 167 men and 149 women, mean age 70+/-12 years (range 22 to 95 years). Median followup was 63+/-25 months. Five-year disease-free survival was 84% overall. Disease-free survival paralleled tumor stage: stage I, 99% (n = 73); stage II, 87% (n = 151); stage III, 72% (n = 92). The predominant pattern of tumor recurrence was distant failure only. Overall locoregional recurrence (locoregional and locoregional plus distant) at 5 years was 4%. Locoregional recurrence paralleled tumor stage: stage I, 0%; stage II, 2%; stage III, 10%. Of the 12 patients who suffered locoregional recurrence, 9 (75%) had T4 primary tumors, N2 nodal disease, or both. Major and minor complications occurred in 93 patients (29%) including: anastomotic leak or intraabdominal abscess (n = 4, 1%); hemorrhage (n = 8, 3%); cardiac complications (n= 17, 5%); pulmonary embolism (n=4, 10%); death (n=2, 1%). Multivariate analysis (Cox proportional hazards) revealed that the only independent predictor of disease-free survival and locoregional control was tumor stage. CONCLUSION: Longterm survival and locoregional control can be achieved for patients with colon cancer, with low morbidity. In the absence of adjacent organ invasion and N2 nodal disease, locoregional recurrence should be a rare event. Just as for rectal cancer, the technical aspects of colectomy for colon cancer deserve renewed attention.

    Title Early Experience with Stapled Hemorrhoidectomy in the United States.
    Date July 2002
    Journal Diseases of the Colon and Rectum
    Excerpt

    INTRODUCTION: We report the early results of patients treated with stapled hemorrhoidectomy, which has recently been introduced into the United States. METHODS: Sixty-eight patients with symptomatic hemorrhoids were treated at two institutions with the Proximate HCS Hemorrhoidal Circular Stapler supplied by Ethicon Endo-Surgery. Patients were prospectively evaluated for functional recovery and postoperative pain on a 1 to 10 scale. RESULTS: There were 45 (66 percent) males and 23 (34 percent) females with a mean age of 56 years and median duration of symptoms of 5 years. The mean operative time was 22.2 minutes. The operation was performed with spinal (50 percent), local (40 percent), or general (10 percent) anesthesia and as an outpatient (56 percent) or overnight admission (44 percent). Ninety-three percent of patients remained asymptomatic with a mean follow-up of 34 weeks, whereas the remaining 7 percent required either surgical excision or rubber band ligation for persistent symptoms. There was no mortality, new incontinence, fecal impaction, or persistent pain. The total morbidity was 19 percent, with urinary retention as the most common complication (12 percent). The mean pain score decreased from 3.6 on postoperative Day 1 to 1.4 at postoperative Day 7. Ninety-nine percent of patients made a complete functional recovery by postoperative Day 7. CONCLUSIONS: Stapled hemorrhoidectomy is safe, effective, and can be performed as an outpatient procedure with local or regional anesthesia. There seems to be minimal postoperative pain and early recovery, although a benefit over traditional hemorrhoidectomy needs to be proven in a randomized trial.

    Title Neoadjuvant External Beam Radiation and Proctectomy for Adenocarcinoma of the Rectum.
    Date January 2002
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: The aim of this study was to determine the survival rate, local failure, and perioperative morbidity in patients with adenocarcinoma of the rectum undergoing curative proctectomy who were felt to have transmural disease on preoperative assessment. Eighty-nine percent of these patients were treated with preoperative external beam radiotherapy. METHODS: The records of 191 consecutive patients undergoing abdominal surgical procedures for primary treatment of rectal cancer were reviewed. The product-limit method (Kaplan-Meier) was used to analyze survival rate and tumor recurrence. RESULTS: One patient was excluded from survival analysis because of incomplete record of tumor stage. The study population comprised 109 males and 81 females, median age 64 (range, 33-91) years. Curative resection was performed in 152 of these 190 patients (80 percent), including low anterior resection with coloproctostomy or coloanal anastomosis (n = 103), abdominoperineal resection (n = 44), Hartmann's procedure (n = 4), and pelvic exenteration (n = 1). Mean follow-up of patients undergoing curative resection was 96 +/- 48 months. Palliative procedures were performed in 38 of 190 patients (20 percent). Perioperative mortality was 0.5 percent (1/190). Complications occurred in 64 patients (34 percent). The anastomotic leak rate was 4 percent (5/128). Disease-free five-year survival rate by pathologic stage was as follows: Stage I, 90 percent; Stage II, 85 percent; Stage III, 54 percent; Stage IV, 0 percent; and no residual tumor, 90 percent. Of the 152 patients treated with curative resection, disease-free survival rate was 80 percent at five years. Preoperative external beam radiation was administered to 135 of these 152 patients (89 percent). Tumor recurred in 32 of 152 patients (21 percent) treated with curative resection. The predominant pattern of recurrence was distant failure only. Kaplan-Meier overall local recurrence (local and local plus distant) at five years was 6.6 percent. The local recurrence rate paralleled tumor stage: Stage I, 0 percent; Stage II, 6 percent; Stage III, 20 percent; and no residual tumor, 0 percent. CONCLUSION: Preoperative external beam radiotherapy and attention to mesorectal dissection can achieve low local recurrence and excellent long-term survival rate in patients with adenocarcinoma of the rectum. Moreover, these goals can be obtained with low morbidity and mortality.

    Title Radiation Therapy for Epidermoid Carcinoma of the Anal Canal, Clinical and Treatment Factors Associated with Outcome.
    Date December 2001
    Journal Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
    Excerpt

    BACKGROUND AND PURPOSE: In recent years, treatment with combined chemotherapy and radiation has become the standard of care for epidermoid carcinoma of the anus. However, optimal radiotherapy techniques and doses are not well established. MATERIALS AND METHODS: During the period 1975-1997, 106 patients with epidermoid carcinoma of the anal canal underwent radiation therapy. Treatment policies evolved from radiation therapy alone or with surgery, to combined chemotherapy and radiation followed by surgery, to combined chemotherapy and radiation. RESULTS: Overall 74% of patients were NED (no evidence of disease) at last follow-up. The most important clinical correlate with ultimate freedom from disease (includes the contribution of salvage surgery) was extent of disease. The 5-year ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15% salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001, Tarone-Ware). There was no difference between planned vs. expectant surgery (5-year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The most important correlate with late toxicity was a history of major pelvic surgery (surgical vs. non-surgical group: P=0.013, Fisher's exact test, two-tailed summation). Thirty-three additional malignancies have been seen in 26 patients. The most common additional malignancies were gynecologic (nine cases), head and neck (six cases), and lung cancer (five cases). CONCLUSIONS: For T1/T2N0 disease, moderate doses of radiation combined with chemotherapy provided adequate treatment. T4N0 and N+ lesions are the most appropriate candidates for investigational protocols evaluating dose intensification. T3N0 tumors may also be appropriate for investigation; however, dose intensification may ultimately prove counterproductive if the cure rate is not improved and salvage surgery is rendered more difficult. The volume of irradiated small bowel should be minimized for patients who have a past history of major pelvic surgery or who (because of locally advanced tumors) may need salvage surgery in the future. Because of the occurrence of additional malignancy, patients with anal cancer should receive general oncologic screening in long-term follow-up.

    Title Treatment of Rectal Adenocarcinoma with Endocavitary and External Beam Radiotherapy: Results for 199 Patients with Localized Tumors.
    Date October 2001
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: Endocavitary radiation (RT) provides a conservative alternative to proctectomy. Although most suitable for small, mobile lesions, patients with less favorable tumors are often referred if they are poor surgical candidates. Knowing the extent to which radiation can control such tumors can be an important factor in making clinical decisions. METHODS AND MATERIALS: One hundred ninety-nine patients, who received endocavitary RT with or without external beam RT (EBRT) during 1981 through 1995, were followed for disease status for a median of 70 months, including deaths from intercurrent causes. In the early years of the study, 21 patients were treated with endocavitary RT alone, the remainder of the patients received pelvic EBRT (usually 45 Gy in 25 fractions) 5-7 weeks before endocavitary RT. RESULTS: Overall, 141 patients (71%) had local control with RT alone. Salvage surgery rendered an additional 20 patients disease free, for an ultimate local control rate of 81%. On multivariate analysis for local control (excluding surgical salvage), the most significant factors were mobility to palpation, use of EBRT, and whether pretreatment debulking of all macroscopic disease had been done (generally a piecemeal, nontransmural procedure). Of 77 cases staged by transrectal ultrasonography, the local control rate with RT alone was 100% for uT1 lesions, 85% (90% with no evidence of disease after salvage) for freely mobile uT2 lesions, and 56% (67% with no evidence of disease after salvage) for uT3 lesions and uT2 lesions that were not freely mobile. CONCLUSIONS: Patients with small mobile tumors that are either uT1 or have only a scar after debulking achieve excellent local control with endocavitary RT. About 15% of mobile uT2 tumors fail RT; therefore, careful follow-up is critical. Small uT3 tumors are appropriate for this treatment only if substantial contraindications to proctectomy are present.

    Title A Phase I/ii Trial of Three-dimensionally Planned Concurrent Boost Radiotherapy and Protracted Venous Infusion of 5-fu Chemotherapy for Locally Advanced Rectal Carcinoma.
    Date September 2001
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02).There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

    Title Pretreatment Clinical Findings Predict Outcome for Patients Receiving Preoperative Radiation for Rectal Cancer.
    Date June 2001
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    BACKGROUND: As a sole modality, preoperative radiation for rectal carcinoma achieves a local control comparable to that of postoperative radiation plus chemotherapy. Although the addition of chemotherapy to preoperative treatment improves the pathologic complete response rate, there is also a substantial increase in acute and perioperative morbidity. Identification of subsets of patients who are at low or high risk for recurrence can help to optimize treatment. METHODS: During the period 1977-95, 384 patients received preoperative radiation therapy for localized adenocarcinoma of the rectum. Ages ranged from 19 to 97 years (mean 64.4), and there were 171 females. Preoperative treatment consisted of conventionally fractionated radiation to 3600-5040 cGy (median 4500 cGy) 6-8 weeks before surgery in 293 cases or low doses of <3000 cGy (median 2000 cGy) immediately before surgery in 91 cases. Concurrent preoperative chemotherapy was given to only 14 cases in this study period. Postoperative chemotherapy was delivered to 55 cases. RESULTS: Overall 93 patients have experienced recurrence (including 36 local failures). Local failures were scored if they occurred at any time, not just as first site of failure. For the group as a whole, the actuarial (Kaplan-Meier) freedom from relapse (FFR) and local control (LC) were 74% and 90% respectively at 5 years. Univariate analysis of clinical characteristics demonstrated a significant (p < 0.05) adverse effect on both LC and FFR for the following four clinical factors: (1) location <5 cm from the verge, (2) circumferential lesion, (3) near obstruction, (4) tethered or fixed tumor. Size, grade, age, gender, ultrasound stage, CEA, radiation dose, and the use of chemotherapy were not associated with outcome. Background of the surgeon was significantly associated with outcome, colorectal specialists achieving better results than nonspecialist surgeons. We assigned a clinical score of 0 to 2 on the basis of how many of the above four adverse clinical factors were present: 0 for none, 1 for one or two, 2 for three or four. This sorted outcome highly significantly (p < or = 0.002, Tarone Ware), with 5-year LC/FFR of 98%/85% (score 0), 90%/72% (score 1), and 74%/58% (score 2). The scoring system sorts the data for both subgroups of surgeons; however, there are substantial differences in LC on the basis of the surgeon's experience. For colorectal specialists (251 cases), the 5-year LC is 100%, 94%, and 78% for scores of 0, 1, and 2, respectively (p = 0.004). For the more mixed group of nonspecialist surgeons (133 cases), LC is 98%, 80%, and 65% for scores of 0, 1, and 2 (p = 0.008). In multivariate analysis, the clinical score and surgeon's background retained independent predictive value, even when pathologic stage was included. CONCLUSIONS: For many patients with rectal cancer, adjuvant treatment can be administered in a well-tolerated sequential fashion-moderate doses of preoperative radiation followed by surgery followed by postoperative chemotherapy to address the risk of occult metastatic disease. A clinical scoring system has been presented here that would suggest that the local control is excellent for lesions with a score of 0 or (if the surgeon is experienced) 1, and therefore sequential treatment could be considered. Cases with a clinical score of 2 should be strongly considered for protocols evaluating more aggressive preoperative treatment, such as combined modality preoperative treatment.

    Title Manometric Squeeze Pressure Difference Parallels Functional Outcome After Overlapping Sphincter Reconstruction.
    Date June 2001
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: This study was designed to evaluate the effectiveness of overlapping anal sphincter reconstruction and to determine the manometric parameters that correlate with a successful functional outcome. METHODS: A retrospective review of patients who had undergone overlapping sphincter reconstruction for anal incontinence from 1988 to 1999 was undertaken. Only patients with preoperative and six-months-postoperative anal manometry were included in this study. Standard statistical tests were used to compare pre- and postoperative findings. RESULTS: A total of 52 overlapping sphincter reconstructions were performed on 49 patients (46 females). The mean age was 44 (+/- standard error, 15.8; range, 20-81) years, with follow-up at six months. Forty-two patients had a history of complicated vaginal delivery (episiotomies, tears, forceps delivery); 36 patients had a history of anal or perineal surgery; and two patients had perianal Crohn's disease. Nine patients (17 percent) had undergone prior sphincter repair. Incontinence grade improved in 37 patients (71 percent), and complete continence returned in 21 patients (40 percent). The presence of a rectovaginal fistula, postoperative complications, previous sphincter repair, and increase in pudendal nerve terminal motor latency did not affect functional outcome (P = not significant). Patients older than 50 years had a better functional outcome than their younger counterparts after sphincter repair (P = 0.02). Although mean maximal squeeze pressure and mean anal sphincter length increased significantly after sphincter reconstruction (P = 0.0006 and 0.004, respectively), only squeeze pressure difference correlated with functional outcome (r = 0.37; P = 0.007). CONCLUSIONS: Overlapping sphincter reconstruction improved anal function in the majority of patients. The most important factor in the return to normal sphincter function is an increase in squeeze pressure.

    Title Neoadjuvant Therapy for Adenocarcinoma of the Rectum: Tumor Response and Acute Toxicity.
    Date May 2001
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: This study was designed to evaluate the down-staging effect and acute toxicity of preoperative radiation and chemoradiation for primary adenocarcinoma of the rectum. METHODS: The results of pretreatment staging with transrectal ultrasound and computed tomography were compared with final histologic stage in 260 consecutive patients who underwent neoadjuvant therapy and proctectomy for primary adenocarcinoma of the rectum. Patients underwent short-course radiation (2,000 cGy in five fractions), long-course radiation (4,500 cGy in 25 fractions), or chemoradiation (4,500 cGy in 25 fractions with concurrent chemotherapy). RESULTS: Down-staging of one or more T stages occurred in 116 of 260 (45 percent) patients overall (short-course radiation 34/82 (42 percent), long-course radiation 55/122 (45 percent), chemoradiation 27/56 (48 percent), P = not significant). Down-staging of one or more N stages occurred in 85 of 178 (48 percent) patients overall (short-course radiation 12/45 (27 percent), long-course radiation 49/86 (57 percent), chemoradiation 24/47 (51 percent), P = 0.003). Complete pathologic response was observed in 16 of 260 (6 percent) patients overall (short-course radiation 4/82 (5 percent), long-course radiation 5/122 (4 percent), chemoradiation 7/56 (13 percent), P = 0.08). Resection with negative margins (distal, proximal, and radial) was achieved in 211 of 227 patients (93 percent) in whom complete radial margin data were available. Permanent stomas were created in 35 percent of patients; temporary stomas were created in 15 percent. Thirty-three Grade 3 or 4 toxicities occurred in 22 of 260 (8 percent) patients overall during neoadjuvant therapy. Toxicity was more frequent in patients receiving chemoradiation (14/56; 25 percent) and long-course radiation (8/122; 7 percent) than in those receiving short-course radiation (0/82; 0 percent), P < 0.0001. Perioperative complications occurred in 93 patients overall (36 percent). The postoperative mortality rate was 0.4 percent (1/260). There was no significant difference in the complication rate between patients treated with short-course radiation (26/82; 32 percent), long-course radiation (46/122; 36 percent), and chemoradiation (21/56; 38 percent). CONCLUSION: Neoadjuvant therapy for adenocarcinoma of the rectum is well tolerated and can produce substantial down-staging and a high curative resection rate. Chemoradiation can achieve high complete pathologic response rates, although toxicity during neoadjuvant therapy is greater than for radiation alone. Short-course radiation can achieve down-staging of both T stage and N stage.

    Title Outcome of Patients with Rectal Adenocarcinoma and Localized Pelvic Non-nodal Metastatic Foci.
    Date October 2000
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: The aim of this study was to evaluate the outcome of patients with primary rectal adenocarcinoma and soft tissue metastatic foci restricted to the pelvis and to determine whether this entity, which is considered N1 disease in the American Joint Committee on Cancer staging system, behaves like completely replaced nodal disease or the first sign of M1 disease. The clinical course for patients with this finding is not well-described in the literature. METHODS: The authors retrospectively reviewed the medical records of 395 patients with rectal adenocarcinoma who received radiation treatment. Eighteen patients had pelvic soft tissue metastatic foci. Exclusions from this study included 1) cases without metastatic pelvic foci; 2) cases of recurrent cancer; 3) cases with known distant metastatic disease as defined by American Joint Committee on Cancer criteria; and 4) cases with extrapelvic metastatic foci. All patients received adjuvant radiotherapy. Thirteen cases received preoperative radiotherapy. Four cases received postoperative radiotherapy. One case received both preoperative and postoperative radiotherapy. Eight cases received chemotherapy. RESULTS: All eighteen patients had T3 or T4 lesions. Thirteen patients had lymph nodes that contained metastatic disease and would therefore have been scored N1 or N2 even without the pelvic tumor implants. Sixteen of 18 (89 percent) patients died of disease after a survival time of 12 to 37 (mean, 25) months. Only 1 of 18 (6 percent) patients was disease free at five years. The other remaining survivor was undergoing palliative therapy for metastatic disease to the lung. This is significantly worse than our institution's experience with T3,4N+ disease after preoperative radiation (5-year survival, 11 vs. 56 percent; P = 0.0002, Generalized Wilcoxon of Breslow). There was a high incidence of local (9/18) and distant (14/18) failure. No other factor, including radiation dose, margin status, chemotherapy, T stage, and number of involved nodes or soft tissue implants, correlated independently with outcome. CONCLUSIONS: Pelvic metastatic foci confer a significantly worse prognosis than other T3,4N+ disease. Such cases should be excluded from prospective trials for localized disease. Although this entity probably represents M1 disease for most patients, survival can be long, and aggressive locoregional and systemic treatment is warranted.

    Title Usefulness of Fdg-pet Scan in the Assessment of Suspected Metastatic or Recurrent Adenocarcinoma of the Colon and Rectum.
    Date June 2000
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: The purpose of this study was to evaluate the clinical efficacy of positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose compared with computed tomography plus other conventional diagnostic studies in patients suspected of having metastatic or recurrent colorectal adenocarcinoma. METHODS: The records of 105 patients who underwent 101 computed tomography and 109 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography scans for suspected metastatic or recurrent colorectal adenocarcinoma were reviewed. Clinical correlation was confirmed at time of operation, histopathologically, or by clinical course. RESULTS: The overall sensitivity and specificity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detection of clinically relevant tumor were higher (87 and 68 percent) than for computed tomography plus other conventional diagnostic studies (66 and 59 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting mucinous cancer was lower (58 percent; n = 16) than for nonmucinous cancer (92 percent; n = 93). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting locoregional recurrence (n = 70) was higher than for computed tomography plus colonoscopy (90 vs. 71 percent, respectively). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting hepatic metastasis (n = 101) was higher than for computed tomography (89 vs. 71 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting extrahepatic metastases exclusive of locoregional recurrence (n = 101) was higher than for computed tomography plus other conventional diagnostic studies (94 vs. 67 percent). 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography altered clinical management in a beneficial manner in 26 percent of cases (26/101) when compared with evaluation by computed tomography plus other conventional diagnostic studies. CONCLUSION: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is more sensitive than computed tomography for the detection of metastatic or recurrent colorectal cancer and may improve clinical management in one-quarter of cases. However, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is not as sensitive in detecting mucinous adenocarcinoma, possibly because of the relative hypocellularity of these tumors.

    Title Use of Endoanal Ultrasound in Patients with Rectovaginal Fistulas.
    Date September 1999
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: The purpose of our study was to define the role of endoanal ultrasound in the evaluation and management of patients with rectovaginal fistula. METHODS: A retrospective review was performed of all patients with rectovaginal fistula who were evaluated by endoanal ultrasound at Barnes-Jewish Hospital at Washington University from 1992 to 1997. RESULTS: Twenty-five females underwent endoanal ultrasound before rectovaginal fistula repair. Mean age was 34 years. Rectovaginal fistulas were caused by obstetric trauma (19 patients; 76 percent), cryptoglandular disease (5 patients; 20 percent), and Crohn's disease (1 patient; 4 percent). Previous rectovaginal fistula repair had been performed in ten patients (40 percent). A history of anal incontinence was present in ten patients (40 percent). Rectovaginal fistula location was above (15 patients), at (7 patients), or below (3 patients) the dentate line. Rectovaginal fistula size was <5 mm (19 patients; 76 percent) or >5 mm (6 patients; 24 percent). Anal manometry revealed decreased sphincter pressures (resting or squeeze) in 12 patients (48 percent). Pudendal nerve latency was abnormal in three patients (9 percent). Endoanal ultrasound identified the rectovaginal fistula in 7 patients (28 percent) and an anterior sphincter defect in 23 patients (92 percent). At surgery sphincter injuries were identified in 23 patients (92 percent). Treatment was either sliding flap repair with anal sphincter reconstruction (22 patients; 88 percent) or sliding flap repair alone (3 patients; 12 percent). Repair of the rectovaginal fistula was successful in 23 patients (92 percent). Complications occurred in 11 patients (44 percent): two recurrent rectovaginal fistulas, five infections, two skin separations, one ectropion, and one hematoma. The two patients with recurrent rectovaginal fistula had prior repairs, and both were subsequently repaired successfully. Of the 11 patients with preoperative anal incontinence, 6 patients (54 percent) were continent and 2 (18 percent) improved after surgery. Cause, size, location, and previous repair of fistula had no effect on final outcome. CONCLUSIONS: Noncontrast endoanal ultrasound was not useful in imaging rectovaginal fistulas and cannot be recommended as a diagnostic or screening tool for the identification of a rectovaginal fistula. However, we recommend that endoanal ultrasound be performed preoperatively in all patients with known rectovaginal fistulas to identify and map occult sphincter defects. Concomitant anal sphincter reconstruction should be considered strongly in patients with rectovaginal fistula and an endoanal ultrasound-documented sphincter defect.

    Title Laparoscopic Vs. Open Abdominoperineal Resection for Cancer.
    Date August 1999
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: The aim of this study was to compare the safety and efficacy of laparoscopic abdominoperineal resection and open abdominoperineal resection for cancer. METHODS: Records of 194 patients who underwent laparoscopic abdominoperineal resection (42 patients) or open abdominoperineal resection (152 patients) at three institutions between 1991 and 1997 were reviewed. Follow-up was through office charts, American College of Surgeons cancer registry, or telephone contact. Tumors included (laparoscopic abdominoperineal resection and open abdominoperineal resection, respectively) adenocarcinoma (86 and 92 percent), squamous (12 and 7 percent), and gastrointestinal stromal (2 and 1.4 percent) types; Stages I (17 and 26 percent), II (24 and 33 percent), III (43 and 32 percent), and IV (14 and 9 percent); and those with invasion of pelvic structures (14 and 16 percent). RESULTS: Laparoscopic abdominoperineal resection was converted to open abdominoperineal resection in 21 percent because of vessel injury (33 percent), poor exposure (22 percent), adhesions (22 percent), inguinal hernia (11 percent), or radiation fibrosis (11 percent). Perineal infections occurred more often in the laparoscopic abdominoperineal resection group (24 vs. 8 percent; P=0.02). Late stoma complications were similar. Mean hospital stay was shorter after laparoscopic abdominoperineal resection (7 vs. 12 days). Radial margins were positive in 12 percent of laparoscopic abdominoperineal resection and 12.5 percent of open abdominoperineal resection specimens. Tumor recurrence was similar for both local (19 and 14 percent) and distant (38 and 26 percent) recurrence. Survival rates were similar by Kaplan-Meier curves, with median follow-up of 19 and 24 months, respectively (P=0.22; log rank). CONCLUSION: Laparoscopic abdominoperineal resection can be performed safely and results in a shorter hospital stay. A randomized, prospective trial is needed to determine the long-term outcome of cancer treatment.

    Title A Practical Approach to Familial and Hereditary Colorectal Cancer.
    Date July 1999
    Journal The American Journal of Medicine
    Excerpt

    Recent genetic research has isolated the primary genetic defect underlying many of the hereditary colorectal cancer syndromes. Obtaining a detailed family history is the first step in identifying individuals at increased risk of developing colorectal cancer. Once identified, individuals and their families may benefit from earlier, more intensified surveillance, prophylactic surgery, cancer risk assessment and education, and genetic testing. Clinicians, especially those with many patients with colorectal cancer in their practice, must be able to address the complex issues associated with the familial and hereditary colorectal cancer syndromes. A well-integrated partnership among colorectal surgeons, gastroenterologists, oncologists, and medical geneticists is necessary to address these complex issues and provide comprehensive medical care.

    Title Colorectal Cancer: Risk Factors and Recommendations for Early Detection.
    Date July 1999
    Journal American Family Physician
    Excerpt

    Spurred by mounting evidence that the detection and treatment of early-stage colorectal cancers and adenomatous polyps can reduce mortality, Medicare and some other payors recently authorized reimbursement for colorectal cancer screening in persons at average risk for this malignancy. A collaborative group of experts convened by the U.S. Agency for Health Care Policy and Research has recommended screening for average-risk persons over the age of 50 years using one of the following techniques: fecal occult blood testing each year, flexible sigmoidoscopy every five years, fecal occult blood testing every year combined with flexible sigmoidoscopy every five years, double-contrast barium enema every five to 10 years or colonoscopy every 10 years. Screening of persons with risk factors should begin at an earlier age, depending on the family history of colorectal cancer or polyps. These recommendations augment the colorectal cancer screening guidelines of the American Academy of Family physicians. Recent advances in genetic research have made it possible to identify persons at high risk for colorectal cancer because of an inherited predisposition to develop this malignancy. These patients require aggressive screening, usually by lower endoscopy performed at an early age. In some patients, genetic testing can guide screening and may be cost-effective.

    Title Proctectomy and Coloanal Anastomosis for Rectal Cancer.
    Date July 1999
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    Fueled by a greater understanding of pelvic physiology along with an improved comprehension of rectal cancer spread, we are now able to offer most patients restoration of intestinal continuity following oncologic proctectomy. Coloanal or ultralow colorectal anastomosis can be performed in most patients with midrectal cancers, provided that anal sphincter function is not impaired preoperatively. Functional results may be improved by construction of a colonic pouch with pouch-anal anastomosis. Temporary fecal diversion, usually with a diverting loop ileostomy, may be prudent, especially in patients undergoing neoadjuvant chemoradiation.

    Title Colonoscopy for Small Adenomas.
    Date April 1999
    Journal Annals of Internal Medicine
    Title Coloenteric Fistula from Chicken-bone Perforation of the Sigmoid Colon.
    Date March 1999
    Journal Surgery
    Title Confirmation That Chromosome 18q Allelic Loss in Colon Cancer is a Prognostic Indicator.
    Date March 1998
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer. METHODS: Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated. RESULTS: LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease. CONCLUSION: Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.

    Title Detection of Recurrent and Metastatic Colorectal Cancer: Comparison of Positron Emission Tomography and Computed Tomography.
    Date February 1998
    Journal Annals of Surgical Oncology
    Excerpt

    BACKGROUND: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). METHODS: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. RESULTS: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. CONCLUSION: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.

    Title Laparoscopic-assisted Ileocolic Resections in Patients with Crohn's Disease: Are Abscesses, Phlegmons, or Recurrent Disease Contraindications?
    Date November 1997
    Journal Surgery
    Excerpt

    BACKGROUND: Because of the inflammatory nature of Crohn's disease, ileocolic resections are often difficult to perform, especially if an abscess, phlegmon, or recurrent disease at a previous ileocolic anastomosis is present. Our goal was to determine whether the above factors are contraindications to a successful laparoscopic-assisted ileocolic resection. METHODS: Between 1992 and 1996, 46 laparoscopic-assisted ileocolic resections were attempted. Fourteen patients had an abscess or phlegmon treated with bowel rest before operation (group I), 10 patients had recurrent Crohn's disease at the previous ileocolic anastomosis (group II), and 22 patients had no previous operation and no phlegmon or abscess associated with their disease (group III). These groups were compared with each other and with 70 consecutive open ileocolic resections for Crohn's disease during the same time period (group IV). RESULTS: Operative blood loss and time were greater in group IV than in groups I, II, and III (245 versus 151, 131, and 195 ml, respectively, and 202 versus 152, 144, and 139 minutes, respectively). Conversion to open procedure occurred in 5 patients (group I, 1 [7%]; group II, 2 [20%]; group III, 2 [9%]). Morbidity was highest in group IV (21% versus 0%, 10%, and 10%, respectively). Only one patient died (group IV, 1%). Length of hospital stay was longest in group IV (7.9 versus 4.8, 3.9, and 4.5 days, respectively). CONCLUSIONS: The laparoscopic-assisted approach to Crohn's disease is feasible and safe with good outcomes. Co-morbid preoperative findings such as abscess, phlegmon, or recurrent disease at the previous ileocolic anastomosis are not contraindications to a successful laparoscopic-assisted ileocolic resection in select patients.

    Title Afferent Limb Obstruction Complicating Ileal Pouch-anal Anastomosis.
    Date June 1997
    Journal Diseases of the Colon and Rectum
    Excerpt

    PURPOSE: Small-bowel obstruction is a common complication after ileal pouch-anal anastomosis (IPAA). Acute angulation of the afferent limb at the pouch inlet is the cause of obstruction in a subset of patients requiring laparotomy. METHODS: Patients were identified from the Lahey Clinic ileoanal pouch registry, a prospective computerized database of all patients who have undergone IPAA since 1980. Records of patients who were identified as having afferent limb obstruction as a cause of bowel obstruction after IPAA were reviewed. RESULTS: A total of 567 patients had undergone total proctocolectomy and ileoanal J-pouch at time of the study. Of 122 patients with one or more episodes of obstruction after IPAA, 48 required operative intervention. Afferent limb obstruction was identified as the cause of obstruction in six patients (12 percent). The most common presentation was recurrent partial obstruction (4 of 6 patients). Contrast small-bowel series and enemas were suggestive of obstruction in four of six patients, the most consistent radiographic finding being small-bowel dilation to the level of the pouch inlet. All patients underwent laparotomy for unresolved obstruction. Intraoperatively, the afferent limb was found to be adherent posterior to the pouch, causing acute angulation at the pouch inlet. Rather than risk injury to the pouch or its mesentery, the obstruction was bypassed by side-to-side anastomosis of the afferent limb to the pouch (enteroenterostomy) in five of six patients. One patient underwent ileostomy only because of technical considerations. Two patients required re-exploration and pexy of the afferent limb to the pelvic sidewall (pouchopexy) to relieve recurrent afferent limb obstruction. CONCLUSION: Afferent limb obstruction should be suspected in patients with recurrent obstruction after IPAA. Bypass of the obstructed segment from distal ileum to the pouch is safe and effective treatment. Because of the risk of recurrent afferent limb angulation, concurrent pouchopexy should be considered.

    Title Importance of Adenomas 5 Mm or Less in Diameter That Are Detected by Sigmoidoscopy.
    Date January 1997
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND: The need for colonoscopy in patients with adenomas 5 mm or less in diameter that are detected by sigmoidoscopy is controversial. METHODS: We prospectively determined the prevalence of proximal colonic neoplasms in asymptomatic patients at average risk for colorectal cancer, each of whose index lesion on screening fiberoptic sigmoidoscopy was a benign adenoma. Polyps found on sigmoidoscopy underwent biopsy, and colonoscopy was recommended to all patients with neoplastic polyps. Rectosigmoid adenomas were classified as diminutive (< or = 5 mm in diameter), small (6 to 10 mm in diameter), or large (> or = 11 mm in diameter). RESULTS: Of 3496 consecutive patients referred for sigmoidoscopy, 311 had neoplastic rectosigmoid polyps; 108 of these patients were excluded from the analysis because of a history of colonic neoplasia, symptoms, prior colonic evaluation, or incomplete follow-up data. The remaining 203 patients made up the study group, and all underwent colonoscopy. Neoplasms were found in the proximal colon in 40 of 137 patients (29 percent) with diminutive index polyps, 15 of 52 patients (29 percent) with small index polyps, and 8 of 14 patients (57 percent) with large index polyps. Advanced neoplasms (adenomas > or = 10 mm in diameter, adenomas with a villous component or moderate-to-severe dysplasia, carcinoma in situ, or frank carcinoma) were found in 8 patients (6 percent), 5 patients (10 percent), and 4 patients (29 percent), respectively. Two patients with diminutive index polyps had proximal carcinoma in situ, and two had proximal stage I carcinomas; one patient with a large index polyp had proximal stage III carcinoma. CONCLUSIONS: The substantial prevalence of proximal colonic neoplasms, including advanced lesions, in asymptomatic average-risk patients with rectosigmoid adenomas < or = 5 mm in diameter warrants colonoscopy in these patients.

    Title Triglyceride-rich Lipoproteins Prevent Septic Death in Rats.
    Date July 1995
    Journal The Journal of Experimental Medicine
    Excerpt

    Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.

    Title Triglyceride-rich Lipoproteins Improve Survival when Given After Endotoxin in Rats.
    Date February 1995
    Journal Surgery
    Excerpt

    BACKGROUND. Triglyceride-rich lipoproteins have been shown to bind bacterial endotoxin and inhibit its activity in vitro and to protect animals from death when administered before a lethal injection of endotoxin. We now demonstrate that triglyceride-rich lipoproteins can neutralize the toxic effects of endotoxin already in circulation. METHODS. Rats were infused with a lethal dose of endotoxin, followed at various time intervals by an infusion of either mesenteric lymph containing nascent chylomicrons (1 gm chylomicron triglyceride/kg) or an equal volume of normal saline solution. Survival was measured at 48 hours. The experiment was then repeated, substituting the synthetic triglyceride-rich lipid emulsion (1 gm/kg) for chylomicrons. We also measured the clearance and tissue distribution of radioiodinated endotoxin in rats treated subsequently with chylomicrons or saline solution. RESULTS. Chylomicron infusions significantly improved survival when given up to 30 minutes after a lethal dose of endotoxin (p < 0.05). Chylomicrons accelerated endotoxin clearance from the blood and increased endotoxin uptake by the liver. The synthetic triglyceride-rich lipid emulsion significantly improved survival when given up to 15 minutes after a lethal dose of endotoxin (p < 0.05). CONCLUSIONS. Triglyceride-rich lipoproteins and synthetic triglyceride-rich lipid emulsions significantly improve survival of rats when given after a lethal dose of endotoxin. Lipoprotein treatment accelerates endotoxin clearance to the liver, which may account for the observed protection. These data suggest a possible therapeutic role for triglyceride-rich lipoproteins or synthetic lipid emulsions in the treatment of the endotoxemia of gram-negative sepsis.

    Title The Protective Effect of Serum Lipoproteins Against Bacterial Lipopolysaccharide.
    Date April 1994
    Journal European Heart Journal
    Excerpt

    Lipoproteins bind and inactivate bacterial endotoxin, both in vitro and in vivo. Both cholesterol ester-rich and TG-rich lipoproteins, and TG-rich lipid emulsions can prevent death in mice when pre-incubated with a lethal dose of endotoxin before intraperitoneal administration. Chylomicrons can also prevent death when given intravenously after endotoxin in rats. The metabolic fate of lipoprotein-bound endotoxin appears to be directed by the lipoprotein particle. When administered with chylomicrons, the plasma clearance and hepatic uptake of endotoxin are enhanced. Endotoxin is shunted preferentially to hepatocytes and away from hepatic macrophages, thereby increasing endotoxin excretion [corrected] in bile. The survival benefit and alterations in metabolism afforded by chylomicrons correlate with a reduction in peak serum levels of tumour necrosis factor (TNF), providing a possible mechanism by which lipoproteins protect against endotoxin-induced death. These findings suggest a possible role for lipoproteins or lipid emulsions in the body's defence against endotoxaemia.

    Title Cigarette Smoke Alters Chylomicron Metabolism in Rats.
    Date September 1993
    Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
    Excerpt

    PURPOSE: Cigarette smoking may exert its atherogenic effect by delaying the plasma clearance of dietary fat and cholesterol, allowing more time for their interaction with the artery wall. To study the effects of smoke on chylomicron metabolism in rats, we examined the metabolic effects of smoke on both whole animals and chylomicron particles in vitro. METHODS: Carbon 14- and hydrogen 3-labeled chylomicrons were injected intravenously into smoke-treated rats and control rats that were not exposed to smoke (sham smoked). Plasma clearance, hepatic uptake, and heart binding were measured. In a second set of experiments, chylomicron particles were exposed to cigarette smoke in vitro by either: (1) passing smoke through chylomicrons suspended in saline solution (SCM) or (2) passing smoke through saline solution alone, then mixing the saline solution with chylomicrons (CM + SS). Normal (non-smoke exposed) rats were infused with either SCM, CM + SS, or control chylomicrons (CCM). Plasma clearance, hepatic uptake, and heart binding were again measured. RESULTS: The initial plasma clearance time of labeled chylomicrons did not differ between smoke-treated and control animals. However, hepatic uptake of chylomicron cholesterol was slower in smoke-treated animals (46.1% +/- 0.9% of injected dose) than in controls (61.5% +/- 2.1%, p < 0.001). In contrast, more labeled chylomicrons remained in the heart of smoke-treated rats than controls (0.89% +/- 0.18% vs 0.45% +/- 0.05%, p < 0.05). Disappearance of 14C-labeled cholesterol from blood was delayed in rats injected with SCM (half-life = 9.0 +/- 0.4 minutes) and CM + SS (half-life = 8.0 +/- 0.4 minutes), compared with the time in rats injected with CCM (6.6 +/- 0.3 minutes, p < 0.05). Hepatic uptake of SCM (40.6% +/- 1.9% of injected dose) and CM + SS (45.0% +/- 1.9%) was less than that of CCM (60.7% +/- 4.4%, p < 0.05). In addition, the binding to the heart increased from 0.97% +/- 0.29% (CCM) to 2.45% +/- 0.30% with the infusion of SCM (p < 0.05). The binding in the heart of CM + SS (0.95% +/- 0.04%) was not different from that of CCM. CONCLUSIONS: These data demonstrate for the first time that cigarette smoke exposure prolongs chylomicron residence time in tissues (heart) and delays hepatic uptake of chylomicron cholesterol in rats. The effect is present when either the animal or the chylomicron particle is exposed to smoke. We hypothesize that prolonged binding of relatively cholesterol-rich chylomicron remnants to endothelial surfaces could create a more atherogenic postprandial milieu.

    Title Chylomicrons Enhance Endotoxin Excretion in Bile.
    Date August 1993
    Journal Infection and Immunity
    Excerpt

    Chylomicrons prevent endotoxin toxicity and increase endotoxin uptake by hepatocytes. As a consequence, less endotoxin is available to activate macrophages, thereby reducing tumor necrosis factor secretion. To determine whether the chylomicron-mediated increase in hepatocellular uptake of endotoxin results in increased endotoxin excretion into bile, we examined bile after endotoxin administration. A sublethal dose (7 micrograms/kg) of 125I-endotoxin was incubated with either rat mesenteric lymph containing nascent chylomicrons (500 mg of chylomicron triglyceride per kg of body weight) or an equal volume of normal saline (controls) for 3 h and then infused into male Sprague-Dawley rats. Bile samples were collected via a common bile duct catheter for 24 h. Infusion of endotoxin incubated with chylomicrons increased biliary excretion of endotoxin by 67% at 3 h (P < or = 0.006) and by 20% at 24 h (P < or = 0.01) compared with infusion of endotoxin incubated in saline. Endotoxin activity, as measured by the Limulus assay, was not detected in the bile of test animals. However, endotoxin activity was detected after hot phenol-water extraction of bile, demonstrating that endotoxin is inactive in the presence of bile but retains bioactivity after hepatic processing. Since the majority of an intravenous endotoxin load has been shown to be cleared by the liver, acceleration of hepatocyte clearance and biliary excretion of endotoxin may represent a component of the mechanism by which chylomicrons protect against endotoxin-induced lethality.

    Title Chylomicrons Alter the Fate of Endotoxin, Decreasing Tumor Necrosis Factor Release and Preventing Death.
    Date April 1993
    Journal The Journal of Clinical Investigation
    Excerpt

    The hypertriglyceridemia of infection was traditionally thought to represent the mobilization of substrate to fuel the body's response to the infectious challenge. However, we have previously shown that triglyceride-rich lipoproteins can protect against endotoxin-induced lethality. The current studies examine the mechanism by which this protection occurs. Rats infused with a lethal dose of endotoxin preincubated with chylomicrons had a reduced mortality compared with rats infused with endotoxin alone (15 vs. 76%, P < 0.001). Preincubation with chylomicrons increased the rate of clearance of endotoxin from plasma and doubled the amount of endotoxin cleared by the liver (30 +/- 1 vs. 14 +/- 2% of the total infused radiolabel, P < 0.001). In addition, autoradiographic studies showed that chylomicrons directed more of the endotoxin to hepatocytes and away from hepatic macrophages. Rats infused with endotoxin plus chylomicrons also showed reduced peak serum levels of tumor necrosis factor as compared with controls (14.2 +/- 3.3 vs. 44.9 +/- 9.5 ng/ml, mean +/- SEM, P = 0.014). In separate experiments, chylomicrons (1,000 mg triglyceride/kg) or saline were infused 10 min before the infusion of endotoxin. Chylomicron pretreatment resulted in a reduced mortality compared with rats infused with endotoxin alone (22 vs. 78%, P < 0.005). Therefore, chylomicrons can protect against endotoxin-induced lethality with and without preincubation with endotoxin. The mechanism by which chylomicrons protect against endotoxin appears to involve the shunting of endotoxin to hepatocytes and away from macrophages, thereby decreasing macrophage activation and the secretion of cytokines.

    Title How Often Do Patients Return to the Operating Room After Colorectal Resections?
    Date
    Journal Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland
    Excerpt

    We sought to identify the rate of re-operation after an index colorectal surgical procedure and potential contributing risk factors.


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