Ronald Bleday

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group protocol 6584

We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival.

Reduction in adhesive small-bowel obstruction by Seprafilm adhesion barrier after intestinal resection.

IntroductionAlthough Seprafilm® has been demonstrated to reduce adhesion formation, it is not known whether its usage would translate into a reduction in adhesive small-bowel obstruction.MethodsThis was a prospective, randomized, multicenter, multinational, single-blind, controlled study. This report focuses on those patients who underwent intestinal resection (n = 1,701). Before closure of the abdomen, patients were randomized to receive Seprafilm® or no treatment. Seprafilm® was applied to adhesiogenic tissues throughout the abdomen. The incidence and type of bowel obstruction was compared between the two groups. Time to first adhesive small-bowel obstruction was compared during the course of the study by using survival analysis methods. The mean follow-up time for the occurrence of adhesive small-bowel obstruction was 3.5 years.ResultsThere was no difference between the treatment and control group in overall rate of bowel obstruction. The incidence of adhesive small-bowel obstruction requiring reoperation was significantly lower for Seprafilm® patients compared with no-treatment patients: 1.8 vs. 3.4 percent (P < 0.05). This finding represents an absolute reduction in adhesive small-bowel obstruction requiring reoperation of 1.6 percent and a relative reduction of 47 percent. In addition, a stepwise multivariate analysis indicated that the use of Seprafilm® was the only predictive factor for reducing adhesive small-bowel obstruction requiring reoperation. In both groups, 50 percent of first adhesive small-bowel obstruction episodes occurred within 6 months after the initial surgery with nearly 30 percent occurring within the first 30 days. Additionally no first adhesive small-bowel obstruction events were reported in Years 4 and 5 of follow-up.ConclusionsThe overall bowel obstruction rate was unchanged; however, adhesive small-bowel obstruction requiring reoperation was significantly reduced by the use of Seprafilm®, which was the only factor that predicted this outcome.

Early results of laparoscopic surgery for colorectal cancer - Retrospective analysis of 372 patients treated by clinical outcomes of Surgical Therapy (Cost) Study Group

PURPOSE: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, −4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.

Symptomatic hemorrhoids: Current incidence and complications of operative therapy

Hemorrhoidal disease affects more than one million Americans per year. We reviewed the treatment pattern for patients who presented with symptomatic hemorrhoids to our large university-affiliated group practice over a 66-month period. Over 21,000 patients presented to the practice with bleeding, thrombosis, or prolapse. Only 9.3 percent of patients required operative therapy. Conservative therapy was given to 45.2 percent of patients, while rubber band ligation was performed on 44.8 percent of patients. We retrospectively reviewed the complications and length of stay for a subset of patients undergoing operative therapy during the 66-month study period. Postoperative urinary complications (retention or infection) were seen in 20.1 percent of patients. Delayed hemorrhage was seen in 2.4 percent of patients. In-hospital length of stay was 2.5 days, which is approximately two days less than the length of stay found in a similar review of our practice in 1978. We conclude that over 90 percent of symptomatic hemorrhoids can be treated conservatively or with rubber band ligation, and, as surgery is reserved for only the most severe cases, complication rates may not decrease. However, we expect that in-hospital length of stay will continue to decrease over the ensuing years.

Prospective evaluation of local excision for small rectal cancers

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancerrelated overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent(4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.

Immediate Reconstruction of the Perineal Wound With Gracilis Muscle Flaps Following Abdominoperineal Resection and Intraoperative Radiation Therapy for Recurrent Carcinoma of the Rectum

Background: Morbidity associated with a nonhealing perineal wound is the most common complication following proctectomy, particularly in the setting of recurrent carcinoma of the rectum and radiation therapy. Immediate reconstruction using the gracilis myocutaneous and muscle flaps significantly reduces the incidence of major infection associated with perineal wound closure. The purpose of this study was to assess the value of immediate reconstruction of the perineal wound using a gracilis flap in patients undergoing abdominoperineal resection and intraoperative radiation therapy.Methods: This study retrospectively reviewed our experience with immediate pelvic reconstruction using gracilis muscle flaps for patients undergoing rectal extirpation and irradiation for recurrent carcinoma of the rectum. From 1990 to 1995, 16 patients underwent abdominoperineal resection (APR) or pelvic exenteration accompanied by immediate wound closure with unilateral or bilateral gracilis muscle flaps. Morbidity and mortality outcomes were compared to those of 24 patients from our institution who, between 1988 and 1992, underwent proctectomy and irradiation for recurrent rectal carcinoma with primary closure of the perineal wound.Results: Major complications (i.e., major infection requiring hospitalization and/or operation) occurred in 2 (12%) of the patients with gracilis flaps versus 11 (46%) of the patients with primary closure (P = .028 by χ2 analysis for flap vs. primary closure). Minor complications (i.e., persistent sinus and subcutaneous abscess) occurred in 4 (25%) of the patients with gracilis flaps versus 5 (21%) of those with primary closure.Conclusion: Immediate perineal reconstruction using the gracilis myocutaneous flap following proctectomy and irradiation for recurrent rectal carcinoma significantly reduces the incidence of major infection associated with perineal wound closure.

Role of virtual computed tomographic colonography in patients with colorectal cancers and obstructing colorectal lesions

PURPOSE: The aim of this study was to assess the ability of computed tomographic colonography to diagnose colorectal masses, stage colorectal cancers, image the proximal colon in obstructing colorectal lesions, and evaluate the anastomoses in patients with previous colorectal surgery. METHODS: We prospectively performed computed tomographic colonography examinations in 34 patients (20 males; mean age, 64.2; range, 19–91 years): 20 patients had colorectal masses (defined at endoscopy as intraluminal masses 2 cm or larger), 7 patients had benign obstructing colorectal strictures, and 7 patients had a prior colorectal resection. Final tumor staging was available in all 16 patients who had colorectal cancers and 15 patients were referred after incomplete colonoscopy. The ability of computed tomographic colonography to stage colorectal cancers, identify synchronous lesions in patients with colorectal masses, and image the proximal colon in patients with obstructing colorectal lesions was assessed. RESULTS: Computed tomographic colonography identified all colorectal masses, but overcalled two masses in patients who were either poorly distended or poorly prepared. Computed tomographic colonography correctly staged 13 of 16 colorectal cancers (81 percent) and detected 16 of 17 (93 percent) synchronous polyps. Computed tomographic colonography overstaged two Dukes Stage A cancers and understaged one Dukes Stage C cancer. A total of 97 percent (87/90) of all colonic segments were adequately visualized at computed tomographic colonography in patients with obstructing colorectal lesions compared with 60 percent (26/42) of segments at barium enema (P<0.01). Colonic anastomoses were visualized in all nine patients, but in one patient, computed tomographic colonography could not distinguish between local tumor recurrence and surgical changes. CONCLUSION: Computed tomographic colonography can accurately identify all colorectal masses but may overcall stool as masses in poorly distended or poorly prepared colons. Computed tomographic colonography has an overall staging accuracy of 81 percent for colorectal cancer and is superior to barium enema in visualizing colonic segments proximal to obstructing colorectal lesions.

Increased risk of early colorectal neoplasms after hepatic transplant in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with an increase in colon and rectal carcinoma. Immunosuppression after transplantation increases the incidence of certain types of tumors. PURPOSE: We reviewed the postoperative course of IBD patients who had undergone hepatic transplantation for primary sclerosing cholangitis to see whether there was an increase in the rate of colorectal neoplasms. METHODS: The charts of 44 patients from two institutions who had undergone a hepatic transplant for primary sclerosing cholangitis were reviewed. Of these 44 patients, 33 had IBD (32 chronic ulcerative colitis, 1 Crohns). Of these 33 patients, 2 had previously undergone total colectomy/proctectomy and 4 died in the perioperative period. The remaining 27 patients had all undergone colonoscopic evaluation just prior to transplant. Postoperatively all patients were given prednisone, cyclosporine, and azathioprine. Minimum follow-up was 12 months; mean follow-up was 39 months. RESULTS: Three of the 27 patients (11.1 percent) developed early colorectal neoplasms (2 cancers, 1 large villous adenoma with severe dysplasia) at 9, 12, and 13 months post-transplant. All three patients were successfully treated with a total colectomy/proctectomy or resection of any remaining colon. These 3 patients had a mean 19-year history of IBD (range, 9–27 years), while the 24 patients without tumors had a mean 18-year history of IBD (range, 6–39 years). CONCLUSION: There is a subset of transplant patients with primary sclerosing cholangitis and IBD who rapidly develop colorectal neoplasms. Frequent surveillance is recommended for IBD patients in the post-transplant period.

Transjugular intrahepatic portosystemic shunt for treatment of bleeding ectopic varices with portal hypertension

PURPOSE: In the setting of hepatic failure and portal hypertension, hemorrhage from stomal and rectal varices is a well-described problem. It has recently been suggested that transjugular intrahepatic portosystemic shunting may be useful in the therapy of bleeding from parastomal or anorectal varices in patients unresponsive to conservative therapy. METHODS: We retrospectively review our institutions experience of five patients with parastomal varices and seven patients with anorectal varices who underwent transjugular intrahepatic portosystemic shunting for hemorrhage refractory to conservative management between 1994 and 1998. RESULTS: The study group consisted of four Childs A, five Childs B, and three Childs C patients. The mean age of the patients was 60.3 (range, 37–85) years. Mean follow-up was 15 (range, 5–27) months. The mean portosystemic pressure gradient before transjugular intrahepatic portosystemic shunting was 17.4±3.1 mmHg. After transjugular intrahepatic portosystemic shunting, the mean portosystemic pressure gradient was reduced to 5.8±1.8 mmHg (P<0.05). Transjugular intrahepatic portosystemic shunting were successful in complete resolution of bleeding in all patients. Three patients had encephalopathic changes after transjugular intrahepatic portosystemic shunting. Two patients died within 30 days of transjugular intrahepatic portosystemic shunting of causes unrelated to the procedure. Four patients required shunt revision within one year of placement. CONCLUSION: The transjugular intrahepatic portosystemic shunting procedure is an effective modality in the therapy of cirrhotic patients with bleeding stomal or anorectal varices unresponsive to conservative management. There is an acceptable procedure-related morbidity and mortality.

Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial

Summary Background Local excision is an organ-preserving treatment alternative for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared to transabdominal rectal resection. Here we investigate the oncologic and functional outcomes of neoadjuvant chemoradiotherapy and local excision for T2N0 rectal cancer. Methods This was a prospective, multi-institutional, single arm phase 2 trial for patients with clinically-staged T2N0 distal rectal cancer, treated with neoadjuvant chemoradiotherapy consisting of capecitabine (original dose 825mg/m2, twice daily, on days 1-14 and 22-35) , oxaliplatin (50mg/m2 weeks 1, 2, 4, 5), and radiation (5 days/week at 1.8 Gy/day for 5 weeks to a dose of 45 Gy, then a boost, for a total dose of 54 Gy) followed by local excision. Due to adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg /m2, twice daily, 5 days/week, for 5 weeks, and the total dose of radiation to 50.4 Gy. Patients were followed at scheduled intervals and evaluated for recurrence and survival. Anorectal function (ARF) and quality of life (QOL) were assessed at baseline and one year after surgery, using validated instruments. The primary endpoint was 3-year disease-free survival for all eligible patients and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumors, and negative resection margins. This trial is registered with ClinicalTrials.gov, number NCT00114231. Findings Seventy-nine eligible patients were accrued to the trial, and started nCRT. Three patients did not complete nCRT or LE per-protocol. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Median follow-up was 56 months. Of the 79 patients, five (6%) developed distant recurrence, and three (4%) recurred locally. All but two underwent salvage surgery. Three-year disease-free survival and overall survival for the entire group were 88% (0.88 (95% CI: 0.81, 0.96) and 95% (95% CI: 0.90, 1.00), respectively. Overall 14 (29%) of 79 patients had grade 3-4 gastrointestinal adverse events, 12 (16%) of 79 patients had grade 3-4 pain as an adverse event, 12 (16%) of 79 patients had grade 3-4 hematological adverse events, and 9 (11%) of 79 patients had grade 3 dermatologic adverse events during chemoradiation. Six (8%) of the 77 patients who had surgery had grade 3 pain, 3(4%) of 77 patients had grade 3-4 hemorrhage, 3 (4%) of 77 patients had gastrointestinal adverse events, 2 (3%) of 77 patients had infectious/febrile neutropenia, 2 (3%) of 77 patients had hematological adverse events, and one (1%) had neurological adverse events. The rectum was preserved in 72 of the 79 (91%) patients. ARF and QOL were unchanged one year after surgery compared to baseline. Interpretation Most patients with T2N0 rectal cancer treated with nCRT and LE achieved organ preservation without deterioration of their quality of life. The estimated 3-year DFS rate was within the defined margin of efficacy. Our data suggest that nCRT followed by LE may be considered as an organ-preserving alternative in carefully selected patients with clinically-staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection.