Segmental Colectomy for Ulcerative Colitis: Is There a Place in Selected Patients Without Active Colitis? An International Multicentric Retrospective Study in 72 Patients.

BACKGROUND AND AIMS: The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. METHODS: All UC patients undergoing SC were included. Postoperative complications according to ClavienDindo's classification, long term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. RESULTS: A TOTAL OF: 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], 'diverticulitis' [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median followup of 40 months, 24/69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2-158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. CONCLUSIONS: After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.

Changing trends in surgery for abdominal Crohn's disease.

AIM: The introduction of biological agents and laparoscopy are, arguably, the most important developments for the treatment of Crohn's disease (CD) in the last two decades. Due to the efficacy of biological agents in treating mild disease, it is likely that the percentage of surgery for complex cases may have increased. The objective of this study was to analyse the changing characteristics and results of the surgical treatment of patients with CD over the past 13 years. METHODS: All patients who underwent abdominal surgery for CD between 2004 and 2016 were retrospectively identified. Data were compared between two periods (2004-2010 and 2011-2016). RESULTS: A total of 908 procedures were performed (48% men, mean age 43 ± 16 years). Demographic and CD characteristics changed significantly over time: comorbidities were more frequent (35% vs 46%, P < 0.0001), and preoperative steroids (28% vs 36%, P < 0.01) and anti-tumour necrosis factor (20% vs 40%, P < 0.0001) treatments were more frequently used in the second period. Smoking (14% vs 8%, P < 0.0001) and use of immunosuppressors (32% vs 22%, P < 0.001) decreased significantly. More cases of penetrating disease (22% vs 32%, P < 0.001) were operated upon in the second period. The laparoscopic approach (49% vs 57%, P < 0.04) was more frequently performed and mean blood loss (167 ± 222 vs 123 ± 243 ml, P < 0.01) decreased significantly. Postoperative morbidity did not change between the two periods. CONCLUSION: Despite a higher incidence of comorbidities and the use of biologics postoperative morbidity remained unchanged. An increased use of laparoscopy and a decreased intra-operative blood loss may have contributed to offsetting the impact of increased comorbidity.

Primary closure of complicated perineal wounds with myocutaneous and fasciocutaneous flaps after proctectomy for Crohn's disease.

BACKGROUND: The purpose of this study is to detail the use of advanced tissue transfer techniques to achieve primary closure of the perineal wound after proctectomy for Crohn's disease. METHODS: Between October 1984 and March 2000, we performed proctectomy with permanent intestinal stoma in 97 patients with Crohn's disease. Twelve of these patients (12.4%) required at least 1 myocutaneous flap to achieve primary closure of the perineal wound. Details of each patient's perioperative course were recorded prospectively. RESULTS: All 12 patients had fistulizing perineal Crohn's disease combined with Crohn's proctitis. Two patients had a simultaneous anal adenocarcinoma. Indications for flap closure included management of large perineal skin defects (n = 11), reconstruction of the posterior vaginal wall (n = 2), and the need to fill a large pelvic dead space (n = 3). (Three patients had a combination of the previous indications). In total, 6 rectus abdominis, 5 gluteus maximus, 1 posterior thigh, 3 chimeric posterior thigh, and 1 latissimus dorsi flaps were performed. Six patients required more than 1 flap. Three patients had complications develop related to the flaps (2 wound hematomas and 1 seroma). Complete perineal healing was achieved in all patients. CONCLUSIONS: Complex tissue flap closure of the perineal wound after proctectomy for perineal complications of Crohn's disease should be considered when simple closure is not possible or when reconstruction of the posterior wall of the vagina is necessary.

Long-term prospective assessment of functional results after proctectomy with coloanal anastomosis.

The objective of this study was to prospectively assess the long-term functional results after restorative proctectomy with coloanal anastomosis for rectal cancer. Thirty consecutive patients (18 males; mean age 59.6 +/- 9.8 years, range 40 to 75 years) underwent proctectomy with coloanal anastomosis for rectal cancer between January 1990 and March 1997. Cancers were located between 5 and 12 cm from the anal verge. Differences existed in the administration of adjuvant therapy and in the kind of anastomotic reconstruction. An 8 cm colonic J-pouch was fashioned in 11 patients. The coloanal anastomosis was protected by a diverting loop ileostomy in 22 patients. All patients were evaluated using a prospective patient-completed protocol to record daily bowel activity over a 1-week period at 3, 6, and 12 months, and yearly thereafter. Mean follow-up extends to 55.5 +/- 27 months (range 7 to 117 months). There were no perioperative deaths. Four patients (13.3%) developed a clinically evident anastomotic dehiscence. Overall, stool frequency decreased from 4.4 +/- 2.5 bowel movements per day at 3 months to 3.0 +/- 2.8 bowel movements per day at 5 years. Patients with a J-pouch had a lower stool frequency in comparison to patients with an end-to-end coloanal anastomosis during the entire study period (from 3.2 +/- 2.2 vs. 3.9 +/- 2.7 bowel movements per day at 6 months to 2.8 +/- 1.9 vs. 3.4 +/- 4.0 bowel movements per day at 5 years; no statistical significance). The percentage of continent patients increased from 50% at 6 months to 75% at 5 years; the percentage of patients with incontinence for solid stool and with frequent incontinence ($7 episodes per week) decreased from 35.7% at 6 months to 12.5% at 5 years. The influence of the type of anastomosis, dehiscence, protective stoma, J-pouch, radiation therapy, and gender was evaluated with univariate analysis. Although there was no statistically significant correlation between any of these variables and the development of incontinence, when incontinence occurred, a history of anastomotic dehiscence increased the number of episodes of incontinence per week and the percentage of episodes of incontinence for solid stools at 6 months, 2 years, and 5 years (P < 0.05 and P < 0.001, respectively); the use of preoperative radiation therapy increased the number of episodes of incontinence per week at 6 months, 1 year, 2 years, and 5 years (P < 0.01) and the percentage of episodes of incontinence for solid stools at 3 and 6 months and 1 and 2 years (P < 0.04); and the presence of a J-pouch increased the number of episodes of incontinence per week at 1 and 2 years (P < 0.03 and 0.005, respectively) and the percentage of episodes of incontinence for solid stools at 2, 3, and 4 years (P < 0.05). These data suggest that the functional results after proctectomy with coloanal anastomosis improve at least over the course of the first 5 postoperative years. Furthermore, when incontinence develops, its severity is made worse by the occurrence of an anastomotic dehiscence, the use of preoperative radiation therapy, and the presence of a J-pouch.

Adenocarcinoma at a strictureplasty site in Crohn's disease: report of a case.

Strictureplasties have proven useful and safe in Crohn's disease. Concerns have been raised, however, about the potential of carcinoma arising at the strictureplasty site. Here the authors report a case of a small-bowel adenocarcinoma developing at the site of a prior strictureplasty in a middle-aged male patient seven years postoperatively in the absence of any other preneoplastic disease of the small bowel. Presenting symptoms were of progressive obstruction after a long period of quiescent disease. With this report comes stronger evidence that adenocarcinoma does occur at strictureplasty sites, raising questions of its long-term safety.

Surgical treatment of anorectal complications in Crohn's disease.

BACKGROUND: The purpose of our study was to elucidate features, surgical procedures, and long-term results in patients with anorectal complications of Crohn's disease. METHODS: Physical findings, surgical treatment, and long-term outcome were recorded prospectively for 224 patients who had anorectal complications of Crohn's disease between October 1984 and May 1999. RESULTS: Presenting complications included abscess (n = 36), fistula-in-ano (n = 51), rectovaginal fistula (n = 20), anal stenosis (n = 40), anal incontinence (n = 11), or a combination of features (n = 66). Twenty-four patients did not undergo surgical treatment; the remaining 200 patients underwent 284 procedures. Ultimately, 139 patients (62%) retained anorectal function; reasons for proctectomy in the remaining 85 patients included disease (n = 66), extensive fistular disease (n = 15), fecal incontinence (n = 2), and tight anal stenosis (n = 1). Patients with rectal disease had a significantly higher rate of proctectomy than patients with rectal sparing (77.6% vs. 13.6%, respectively, P<.0001). In the absence of rectal involvement, patients with multiple complications had a significantly higher rate of proctectomy than patients with single complications (23% vs. 10%, P<.05). CONCLUSIONS: A wide spectrum of surgical techniques is required for the management of the diverse anorectal complications of Crohn's disease. Complete healing and control of sepsis can be achieved in the majority of patients. Active rectal disease and multiple complications significantly increase the need for proctectomy.

Hepatic resection: effective treatment for primary and secondary tumors.

BACKGROUND: Hepatic resection is an accepted therapeutic modality for isolated colorectal metastases (CRM) and primary hepatobiliary cancers (PC). Controversy continues regarding the safety, efficacy, and appropriateness of resection for noncolorectal metastases (NCM). METHODS: A retrospective review of 167 resections in 160 patients was performed to evaluate the impact of demographics and perioperative data on survival and recurrence. Statistical analyses were performed by Student t test, analysis of variance, and Kaplan-Meier survival estimates. RESULTS: Resections were performed for CRM, 110 of 167 (66%), NCM, 31 of 167 (19%), and PC, 26 of 167 (15%). The interval from primary to metastases was significantly longer in the NCM group than the CRM group (34.7+/-45.1 vs. 18.7+/-23.7 months; P<.01). Mean number of lesions was not different between groups; however, NCM were larger than CRM (5.9+/-4.5 vs 4.5+/-2.9 cm; P<.05). Operative complications were significantly greater for PC (54%) versus CRM and NCM (21% and 19%, respectively; P<.01), although length of stay was similar between groups. Perioperative mortality was 2%. Actuarial survival at 1 year, 3 years, and 5 years was CRM 91%, 54%, and 40%, PC 75%, 60%, and 38%, and NCM 68%, 36%, and not available, respectively (CRM vs. NCM; P<.01 at 3 years). CONCLUSIONS: Hepatic resection for primary and secondary malignancy can be performed with minimal morbidity and mortality. Resection of NCM is associated with a lower overall survival compared with CRM and PC. The disease-free interval from resection of the primary to metastasectomy is prolonged and hepatic recurrence infrequent after resection in the NCM group. These results suggest that tumor biology is a critical determinant of outcome after hepatic resection of primary and secondary hepatic tumors.

Side-to-side isoperistaltic strictureplasty in extensive Crohn's disease: a prospective longitudinal study.

OBJECTIVE: To report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn's disease. METHODS: Between January 1992 and April 1999, the authors operated on 469 consecutive patients for Crohn's disease of the small bowel. Seventy-one patients (15.1%) underwent at least one strictureplasty; of these, 21 (4.5%; 12 men, 9 women; mean age 39) underwent an SSIS. The long-term changes occurring in the SSIS were studied radiographically, endoscopically, and histopathologically. RESULTS: The indication for surgical intervention was symptomatic partial intestinal obstruction in each of the 21 patients. Fourteen SSISs were constructed in the jejunum, four in the ileum, and three with ileum overlapping colon. The average length of the SSIS was 24 cm. Performance of an SSIS instead of a resection resulted in preservation of an average of 17% of small bowel length. One patient suffered a postoperative gastrointestinal hemorrhage. All patients were discharged on oral feedings after a mean of 8 days. In all cases, SSIS resulted in resolution of the preoperative symptoms. With follow-up extending to 7.5 years in 20 patients (one patient died of unrelated causes), radiographic, endoscopic, and histopathologic examination of the SSIS suggests regression of previously active Crohn's disease. CONCLUSIONS: SSIS is a safe and effective procedure in patients with extensive Crohn's disease. The authors' results provide radiographic, endoscopic, and histopathologic evidence that active Crohn's disease regresses at the site of the SSIS.

Initial presentation with stage IV colorectal cancer: how aggressive should we be?

HYPOTHESIS: The appropriate surgical treatment of patients with colorectal cancer who are found on initial presentation to have stage IV disease is controversial. With presumed limited life expectancy, the role of primary colon or rectal resection has been questioned, as has the utility of synchronous hepatic resection. DESIGN: A retrospective chart review. SETTING: The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS: One hundred twenty patients were identified through The University of Chicago Hospitals Tumor Registry whose initial presentation showed stage IV colorectal cancer and who underwent laparotomy. MAIN OUTCOME MEASURES: The primary end points of the study were perioperative morbidity and mortality and overall survival. RESULTS: Median survival and 5-year survival were 14.4 months and 10%, respectively. Survival was greater for patients younger than 65 years than for those who were aged 65 years or older (18.3 vs 9.8 months; P = .007). Carcinomatosis was associated with significantly decreased survival when compared with less extensive stage IV disease (6.7 vs 18.1 months; P<.001). Patients who underwent any form of resection of hepatic metastases achieved a survival advantage over those with unresectable liver lesions (median survival, 29.6 vs 10.2 months; P<.001). Overall, 27 patients (22.5%) developed postoperative complications. Seven patients (5.8%) died during the postoperative period. CONCLUSIONS: Age of 65 years or older, carcinomatosis, and extensive (bilobar) liver involvement are associated with decreased survival and increased postoperative morbidity and mortality and may negate any potential benefit patients derive from resection of the primary lesion. A substantial number of patients with synchronous hepatic metastases have protracted survival that justifies resection of the primary colorectal tumor at initial presentation. Despite the presence of stage IV disease, resection of the primary tumor and, when feasible, liver metastases is indicated.

Restorative proctocolectomy with J-pouch ileoanal anastomosis.

Restorative proctocolectomy with ileoanal anastomosis, complemented by a pouch formed with the last foot of terminal ileum, is the procedure of choice for patients in need of surgical treatment for ulcerative colitis and familial polyposis. The procedure has undergone many technical modifications that have ensured a very high degree of continence and an acceptable number of daily bowel movements. Herein we describe the operative technique we use in the majority of our patients, a restorative proctocolectomy with hand-sewn J-pouch ileoanal anastomosis with protecting ileostomy. We also comment on the immediate postoperative care and on the long-term functional results.

Apoptotic and mitotic indices predict survival rates in lymph node-negative colon carcinomas.

An imbalance between apoptosis and mitosis is believed to underlie colon cancer development and progression. These processes regulate the growth of normal and neoplastic epithelia, and in tumors, may confer prognostic information. To test this hypothesis, we determined apoptotic and mitotic indices (AI, MI) by morphology in H&E sections of 154 lymph node-negative, sporadic colon carcinomas. The relationship of these indices to genetic (p53 and Bcl-2) and biological features (DNA ploidy and cell kinetics) and patient survival rates was determined. Tumor features were compared in proximal and distal tumors, given postulated differences in their pathogenesis. Bcl-2 and p53 proteins were examined using immunohistochemistry and DNA ploidy and proliferative indices (PIs) by flow cytometry. Tumor features were dichotomized for analysis of relapse-free survival and overall survival (OS) rates using a Cox proportional hazards model. Median patient follow-up was 8.8 years. The median AI and MI were 1.2% (0-7.6) and 0.40% (0-1.8), respectively, and did not differ by tumor site. AI correlated with histological grade (P = 0.03); MI correlated with PI (P = 0.02) and inversely with Bcl-2 in distal tumors (P = 0.02). p53 and Bcl-2 expression were detected in 52 and 53% of tumors, respectively. Distal tumor site was associated with aneuploidy (P = 0.001), p53 (P = 0.001), and PI > 15% (P = 0.002). In a univariate analysis, colon cancers with high MIs (>0.5%) had a poor prognosis (P = 0.04). Bcl-2 overexpression (>20% + tumor cells) was associated with more favorable OS (P = 0.04). The association of ploidy and PI with outcome was of borderline significance for all tumors; however, diploidy predicted better survival in proximal cancers. In distal cancers, low AIs (< or = 0.25%) and high MIs (>0.5%) were adverse prognostic markers. After adjustment for other variables, an increased MI predicted shorter OS with a hazard ratio (HR) for death of 2.70; 95% confidence interval (CI) was 1.23-5.91 (P = 0.01). Expression of Bcl-2 was associated with more favorable OS (HR, 0.46; 95% CI, 0.21-1.0; P = 0.06). In proximal cancers, Bcl-2 expression was the most important predictor of OS (HR, 0.17; 95% CI, 0.03-0.85; P = 0.03). In distal tumors, low AIs (HR, 3.33; 95% CI, 1.27-9.09; P = 0.01) and high MIs predicted poor survival. In conclusion, increased mitosis and low or absent Bcl-2 expression are significant risk factors for death in node-negative colon cancers, as are low rates of apoptosis in distal tumors. If validated prospectively, our results may identify patient subsets than can benefit from adjuvant chemotherapy.

The implications of acute pouchitis on the long-term functional results after restorative proctocolectomy.

A prospective study was conducted to determine the implications of acute pouchitis on the long-term functional results of restorative proctocolectomy with J-pouch ileoanal anastomosis (IPAA). Between July 1988 and June 1996, 137 consecutive patients underwent IPAA for treatment of ulcerative colitis. 127 patients (93%) have been available for follow-up. All patients completed diaries detailing bowel habits over a 7-day period at 3, 6, 9, 12, 18, 24 months, and yearly after reestablishment of intestinal continuity. Diaries were completed only during time periods in which patients were not suffering from acute symptomatic pouchitis. Patients with chronic pouchitis (n = 7) were excluded from this study leaving 120 patients for analysis. Fifty patients suffered at least one episode of pouchitis (Pouchitis Group). Seventy patients never had pouchitis (No Pouchitis Group). Patients with a history of pouchitis having significantly more bowel movements per day were more likely to ever have minor incontinence (75% vs. 45%, p < 0.005) or major incontinence (37% vs. 17%, p < 0.02). The stools of Pouchitis Group were less likely to be formed (24% vs. 31%, p < 0.001). Pouchitis Group patients also were more likely to wear a protective pad during the day (21% vs. 7% p < 0.04) or during the night (40% vs. 13%, p < 0.001). Even in the absence of clinically active pouchitis, patients who have suffered at least one episode of pouchitis have a poorer long-term functional result after IPAA. The results of this study suggest that ileal pouchitis may represent a chronic condition that displays episodic symptomatic exacerbations.

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced pancreatic carcinoma: a University of Chicago phase II consortium study.

BACKGROUND/OBJECTIVES: Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy. RESULTS: Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively. CONCLUSION: In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.

Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group.

OBJECTIVE: The study was conducted to determine whether the performance of an extended lymphadenectomy and retroperitoneal soft-tissue clearance in association with a pancreatoduodenal resection improves the long-term survival of patients with a potentially curable adenocarcinoma of the head of the pancreas. SUMMARY BACKGROUND DATA: The usefulness of performing an extended lymphadenectomy and retroperitoneal soft-tissue clearance in conjunction with a pancreatoduodenal resection in the treatment of ductal adenocarcinoma of the head of the pancreas is still unknown. Published studies suggest a benefit for the procedure in terms of better long-term survival rates; however, these studies were retrospective or did not prospectively evaluate large series of patients. MATERIALS AND METHODS: Eighty-one patients undergoing a pancreatoduodenal resection for a potentially curable ductal adenocarcinoma of the head of the pancreas were randomized to a standard (n = 40) or extended (n = 41) lymphadenectomy and retroperitoneal soft-tissue clearance in a prospective, multicentric study. The standard lymphadenectomy included removal of the anterior and posterior pancreatoduodenal, pyloric, and biliary duct, superior and inferior pancreatic head, and body lymph node stations. In addition to the above, the extended lymphadenectomy included removal of lymph nodes from the hepatic hilum and along the aorta from the diaphragmatic hiatus to the inferior mesenteric artery and laterally to both renal hila, with circumferential clearance of the origin of the celiac trunk and superior mesenteric artery. Patients did not receive any postoperative adjuvant therapy. RESULTS: Demographic (age, gender) and histopathologic (tumor size, stage, differentiation, oncologic clearance) characteristics were similar in the two patient groups. Performance of the extended lymphadenectomy added time to the procedure, although the difference did not reach statistical significance (397 +/- 50 minutes vs. 372 +/- 50 minutes, p > 0.05). Transfusion requirements, postoperative morbidity and mortality rates, and overall survival did not differ between the two groups. When subgroups of patients were analyzed, using an a posteriori analysis that was not planned at the time of study design, there was a significantly (p < 0.05) longer survival rate in node positive patients after an extended rather than a standard lymphadenectomy. The survival curve of node positive patients after an extended lymphadenectomy could be superimposed onto the curves of node negative patients. Survival curves in node negative patients did not differ according to the magnitude of the lymphadenectomy. Multivariate analysis of all patients showed that long-term survival was affected by tumor differentiation (well vs. moderately vs. poorly differentiated, p > 0.001), diameter (< or = 2.0 cm. vs. > 2.0 cm., p < 0.01), lymph node metastasis (absent vs. present, p < 0.01) and need for 4 or more units of transfused blood (< 4 vs. > or = 4, p <0.01). CONCLUSIONS: The addition of an extended lymphadenectomy and retroperitoneal soft-tissue clearance to a pancreatoduodenal resection does not significantly increase morbidity and mortality rates. Although the overall survival rate does not differ in the two groups, there appears to be a trend toward longer survival in node positive patients treated with an extended rather than a standard lymphadenectomy.

Selective expression of carcinoembryonic antigen promoter in cancer cell lines: targeting strategy for gene therapy in colorectal cancer.

PURPOSE: This study was designed to characterize the mechanisms regulating the expression of the human carcinoembryonic antigen promoter (pCEA), in terms of tissue-specific targeting for gene therapy. The promoter was subcloned to a luciferase reporter gene (pCEA/Luc) in our laboratory and compared with a virally controlled luciferase vector (pSV40/Luc). METHODS: Four human cancer cell lines (HeLa, SW480, Caco2, and SW1116) were transfected with either pCEA/Luc or pSV40/Luc. Cells were treated with interferon-gamma and assayed at 72 hours after treatment. Carcinoembryonic antigen level was measured by enzyme immunoassay. Luciferase expression was measured at 48 hours and one week after transfection by luminometry. RESULTS: Luciferase activity after transfection with pCEA/Luc was higher in CEA-positive cells than in CEA-negative cells (P < 0.0001). pCEA/Luc demonstrated higher activity than pSV40/Luc in CEA-positive cells (P < 0.0001), but not in CEA-negative cells. In Caco2 cells, which before confluence are CEA-negative, luciferase expression increased on reaching confluence (P < 0.0001). Well to moderately differentiated cells responded to the interferon-gamma treatment, but the increase in CEA secretion did not correspond to an increase in pCEA/Luc expression. CONCLUSIONS: The expression of pCEA correlates well with the CEA production by the specific cell line offering a potential tissue-specific targeting strategy for colon cancer gene therapy. Furthermore, the tissue-specific CEA promoter has a higher and more persistent activity in CEA-positive human cancer cells than a viral promoter. The lack of response to interferon-gamma treatment suggests a different mechanism of action for interferon-gamma other than directly interacting with the promoter.

Total mesenteric excision in the surgical treatment of rectal cancer: a prospective study.

BACKGROUND: Total mesorectal excision has been advocated in conjunction with low anterior or abdominoperineal resection as the optimal surgical treatment for rectal cancer. It involves removal of the entire rectal mesentery as an intact unit and maximizes the likelihood of obtaining a negative circumferential margin. OBJECTIVES: To prospectively validate the efficacy of total mesorectal excision in obtaining locoregional control, to identify the perioperative factors influencing the selection of either a sphincter sparing or a sphincter ablating procedure, and to identify independent factors that may influence long-term prognosis in rectal cancers. SETTINGS: Tertiary referral center. PATIENTS: Seventy-three consecutive patients with rectal cancer located within 10 cm of the anal verge were treated from 1984 to 1997 by the senior author (F.M.). Sixty-five patients form the basis of our analysis after the exclusion of 7 patients who had their cancer removed transanally and 1 patient who had a permanent diverting stoma as the only procedure. RESULTS: Twenty-six patients underwent a sphincter ablating procedure; 39 underwent a sphincter sparing procedure. Operative mortality was 1.5%. Follow-up was complete in 64 patients (39+/-30 months; range, 3-126 months). Five-year actuarial survival rates were 88% for the 34 patients with stage I and II adenocarcinoma and 65% for the 22 patients with stage III adenocarcinoma. The local recurrence rate was 6.2% overall, but only 3.1% in the potentially curable group (stages I-III). When only patients who did not receive adjuvant chemoradiation therapy were considered (n=23), local recurrence rate was 8.3% overall and 0% in the potentially curable group. Tumor stage (P=.04) and vascular and/or lymphatic invasion (P=.002) were statistically significant in their association with survival. Circumferential lesions (P<.001), gross invasion of contiguous organs (P<.001) and distance from the anal verge of less than 5 cm (P=.01) were statistically significant in their association with the choice of a sphincter ablating procedure. CONCLUSIONS: This study confirms the efficacy of total mesorectal excision in minimizing locoregional recurrence rates and confirms the well-established prognostic value of stage and microinvasion. Moreover, it indicates that circumferential lesions, distance from anal verge, and gross invasion of contiguous organs are significant perioperative factors in the selection of the type of surgical procedure.

Strictureplasty for Crohn's disease: techniques and long-term results.

Strictureplasty for treatment of symptomatic intestinal strictures secondary to Crohn's disease is being performed with increasing frequency. To determine the overall clinical results after strictureplasty for Crohn's disease, all patients undergoing this procedure were prospectively studied. Between 6/1/89 and 2/1/97, 57 Crohn's disease patients underwent 60 operations utilizing strictureplasties. A total of 109 strictureplasties were performed (90 Heineke-Mikulicz, 6 Finney, and 13 side-to-side isoperistaltic). The 30-day perioperative morbidity was 12%, with complications being less common for patients undergoing elective versus unscheduled operations (p < 0.002). Recurrence of Crohn's disease requiring operation was seen in seven patients after a mean follow-up of 38 months. The estimated cumulative recurrence rate after 2 years was 15 +/- 6% (+/- standard error) and 22 +/- 10% at 5 years. A recurrence developed at the site of the previous strictureplasty in only five cases. Strictureplasty is a safe, effective means of providing long-term surgical palliation to selected patients with Crohn's disease. Perioperative complication rates are comparable to those seen with standard surgical treatment, and recurrences are not excessive.

Prospective study of the features, indications, and surgical treatment in 513 consecutive patients affected by Crohn's disease.

BACKGROUND: The aim of this prospective study was to elucidate the features, indications, and surgical treatment in patients affected by complications of Crohn's disease. METHODS: Between January 1985 and July 1996, 513 consecutive patients (248 male, 265 female; mean age, 38 years) were operated on for 542 occurrences of Crohn's disease. Data were collected prospectively. RESULTS: Indications for abdominal surgery were often multiple but included failure of medical management (n = 220), obstruction (n = 94), intestinal fistula (n = 68), mass (n = 56), abdominal abscess (n = 33), hemorrhage (n = 7), and peritonitis (n = 9). Four hundred sixty-four abdominal procedures were performed, necessitating 425 intestinal resections and 97 stricture plasties. The use of stricture plasty was more common in the second half of the study (16.0% versus 7.3%, second half versus first half; p < 0.01). Perioperative complications occurred in 75 of the 464 abdominal operations (16%). There were no deaths. One hundred thirty patients (25%) required operation for perineal complications of Crohn's disease. The presence of Crohn's disease in the rectal mucosa was associated with a higher risk for permanent stomas in patients requiring operation for treatment of perianal Crohn's disease (67% versus 11%; p < 0.001). CONCLUSIONS: Patterns of surgical treatment in Crohn's disease are changing, with more emphasis on nonresectional options. The presence of rectal involvement significantly increases the need for a permanent stoma in patients with perianal Crohn's disease.

Incidence and therapeutic implications of synchronous colonic pathology in colorectal adenocarcinoma.

BACKGROUND: The presence of synchronous benign and malignant colonic pathology may influence the magnitude of surgery for colorectal adenocarcinoma. The aim of this prospective study was to quantitate the need for a more extensive surgical procedure because of synchronous pathology in colorectal cancer patients. METHODS: Between 1984 and 1996, 235 consecutive patients were treated for colorectal adenocarcinoma. Preoperative survey of the colon in 228 patients included colonoscopy (91%) and double contrast barium enema (35.7%). Seven patients were excluded for incomplete preoperative survey because of perforating or obstructing colon carcinoma or acute ulcerative colitis. RESULTS: One hundred four patients (45.6%) had the following synchronous colonic lesions: benign polyps (68 patients, 29.8%), diverticular disease (30, 13.1%), ulcerative colitis (10, 4.4%), synchronous adenocarcinoma (8, 3.5%), and Crohn's colitis (3, 1.3%). Pathologic examination demonstrated three additional synchronous adenocarcinomas for a total of 11 patients (4.9%). Twenty-five (11%) required more extensive surgery than dictated by the primary cancer. Of these 25 patients, 17 had a benign or premalignant condition associated with their carcinoma and 8 had a synchronous carcinoma. Seventeen patients underwent a sphincter-saving procedure. Of the remaining eight patients requiring sphincter ablation, seven were needed because of a synchronous nonmalignant lesion, rather than because of the primary tumor. CONCLUSIONS: In our patient population, the incidence of synchronous colorectal lesions was 45.6%. Synchronous colorectal cancer occurred in 4.9%. In 11%, the presence of synchronous colorectal lesions made the surgical procedure more extensive than that dictated by the primary cancer, and in 3%, the need for a sphincter ablating procedure was dictated by a synchronous nonmalignant lesion.