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Background: Variabilities of both oncologic and functional outcomes are major problems after rectal cancer treatment. Standardized techniques might produce more consistent surgical quality. This study reports outcomes during a 20-year period resulting from a systematically applied surgical approach., Methods: Between 1990 and 2010, 368 rectal cancer patients, treated with total mesorectal excision conducted in a standardized, stepwise approach, were prospectively entered into a database. Influence of time period, surgeon, tumor and anastomotic height, and resection type was evaluated with multivariable regression analyses adjusting for age, disease stage, diversion, and (neo)adjuvant treatment. Function outcome questionnaires were sent to 50 patients at least 5 years after surgery., Results: Five-year overall survival was 76.4 %. Local and distant recurrence rates were 5.2 % and 22.1 %. Anastomotic leakage occurred in 5.4 % of patients treated with low anterior resection (n = 259). Time period, surgeon, tumor and anastomotic height, diversion, and abdominoperineal resection were not independent risk factors for any of these outcome measures. Both preoperative and postoperative radiotherapy were independently associated with increased risk of metastases (P = 0.035, hazard ratio (HR) = 3.04; and P = 0.029, HR = 3.59). Function questionnaires were completed by 38 of 50 patients (76 %). One of 13 nonirradiated patients reported mild fecal incontinence compared with 20 of 25 irradiated patients reporting mostly moderate-severe incontinence (P < 0.001)., Conclusions: Systematically applied surgical dissection results consistently in excellent oncologic outcomes with enhanced function outcomes. The findings suggest that in the presence of highly disciplined surgery, radiotherapy might make a smaller contribution to oncologic outcome, while leading to serious adverse effects.

Objective: To investigate the efficacy and safety of alvimopan, 12 mg, administered orally 30 to 90 minutes preoperatively and twice daily postoperatively in conjunction with a standardized accelerated postoperative care pathway for managing postoperative ileus after bowel resection., Design, Setting, and Patients: This multicenter, randomized, placebo-controlled, double-blind, phase 3 trial enrolled adult patients undergoing partial bowel resection with primary anastomosis by laparotomy and scheduled to receive intravenous, opioid-based, patient-controlled analgesia. A standardized accelerated postoperative care pathway including early ambulation, oral feeding, and postoperative nasogastric tube removal was used to facilitate gastrointestinal (GI) tract recovery in all of the patients., Main Outcome Measures: The primary end point was time to GI-2 recovery (toleration of solid food and first bowel movement). Secondary end points included time to GI-3 recovery (toleration of solid food and first flatus or bowel movement), hospital discharge order written, and actual hospital discharge. Postoperative length of hospital stay based on calendar day of hospital discharge order written, opioid consumption, and overall postoperative ileus-related morbidity were recorded., Results: Alvimopan, 12 mg, was well tolerated and significantly accelerated GI-2 recovery, GI-3 recovery, and actual hospital discharge compared with a standardized accelerated postoperative care pathway alone (hazard ratio = 1.5, 1.5, and 1.4, respectively; P < .001 for all). Time to hospital discharge order written as measured by hazard ratio (1.4) and by postoperative calendar days (mean for alvimopan, 5.2 days; mean for placebo, 6.2 days) was also accelerated. Opioid consumption was comparable between groups, and alvimopan was associated with reduced postoperative ileus-related morbidity compared with placebo., Conclusions: Alvimopan, 12 mg, administered 30 to 90 minutes before and twice daily after bowel resection is well tolerated, accelerates GI tract recovery, and reduces postoperative ileus-related morbidity without compromising opioid analgesia.

Retained foreign body is a recognized complication of abdominal, pelvic, and thoracic surgery and a cause of medical malpractice. Efforts to reduce its incidence include safe exposure and the use of fewer laparotomy pads. The EZ DASH is an absorbent 12-thickness laparotomy pad covering a malleable stainless steel mesh, providing both the needed retraction and a reduction in the use of individual pads. EZ DASH has been introduced into clinical use in 183 consecutive cases by specialty surgeons (colorectal, gynecology, and gynecologic oncology services) at multiple medical centers. The retractor may be shaped to the individual needs of an operating field, eg, the pelvis, and the small bowel secured behind the retractor, held in place by the tension of its mesh and the security of the abdominal wall. Positioning has been intuitive and secure, and the intraoperative use of sponges and of operating time have both been noticeably reduced. Among 183 cases, 91% of uses were felt to reduce OR time by or=10 minutes. Ninety-three percent of EZ DASH cases used fewer individual laparotomy pads for small bowel retraction. Ninety-five percent of uses suggested a value added to the case by the operating surgeon with an expressed desire to use the product repeatedly. The EZ DASH is a simple method of obtaining small bowel retraction and laparotomy pad absorption with a reduction in the need for individual pads, providing excellent exposure for the operative field and reducing the risk of retained foreign body.

Purpose: Locoregional recurrence after resection of colon carcinoma is an uncommon and difficult clinical problem. Outcome data to guide surgical management are limited. This investigation was undertaken to review our experience with surgical resection for patients with locoregional recurrence colon cancer, determine predictors of respectability, and define prognostic factors associated with survival., Patients and Methods: A prospective database was queried for patients who had recurrent colon cancer between January 1991 and October 2002. Patients were selected for analysis if they had either isolated resectable locoregional recurrence or concomitant resectable distant disease. Disease-specific survival analysis was performed with the Kaplan-Meier actuarial method, and factors associated with outcome were determined by the log-rank test and Cox regression., Results: During this period of time, 744 patients with recurrent colon cancer were identified and 100 (13.4 percent) underwent exploration with curative intent for potentially resectable locoregional recurrence: 75 with isolated locoregional recurrence, and 25 with locoregional recurrence and resectable distant disease. The median follow-up for survivors was 27 months. Locoregional recurrence was classified into four categories: anastomotic; mesenteric/nodal; retroperitoneal; and peritoneal. Median survival for all patients was 30 months. Fifty-six patients had an R0 resection (including distant sites). Factors associated with prolonged disease-specific survival included R0 resection (P < 0.001); age <60 years (P < 0.01); early stage of primary disease (P = 0.05); and no associated distant disease (P = 0.03). Poor prognostic factors included more than one site of recurrence (P = 0.05) and involvement of the mesentery/nodal basin (P = 0.03). The ability to obtain an R0 resection was the strongest predictor of outcome, and these patients had a median survival of 66 months., Conclusion: Salvage surgery for locoregional recurrence colon cancer is appropriate for select patients. Complete resection is critical to long-term survival and is associated with a single site of recurrence, perianastomotic disease, low presalvage carcinembryonic antigen level, and absence of distant disease.

The main objectives of surgery for rectal cancer are cure and the prevention of local or pelvic recurrence. Preservation of pelvic autonomic functions are important associated goals that have influenced the design of the operation. These changes began with modifications to the art of lateral pelvic lymphadenectomy, and with the introduction of sharp pelvic dissection along anatomical pelvic fascial planes for rectal cancer in the mid-1970s. These changes evolved to include deliberate autonomic nerve preservation as a part of the operation that was ultimately reported as TME with ANP [1]. While it is a small nuance. dissection was generally directed to the widest possible pelvic margin--medial to the autonomic nerves, as opposed to just peripheral to the mesorectum. Both sexual and urinary functions are complex. and patients undergoing surgery for rectal cancer may have differing baseline levels of function. Pre-existing benign prostatic hypertrophy or stress incontinence are common physical conditions. Patients bring personal or cultural attitudes to the subject of sexual function with advancing years. in a population with a median age in the mid-sixties. Other health issues such as coronary artery or peripheral vascular atherosclerotic disease, diabetes mellitus. smoking or alcohol intake, or the use of medications to treat these conditions, may influence sexual function. Radiation therapy, frequently used in conjunction with chemotherapy in the treatment of rectal cancer, may be associated with its own incidence of impotence caused via a different mechanism. While radiation may affect the vasa nervosa of the autonomic nerves, leading to fibrosis and dysfunction. radiation therapy may also be associated with smooth muscle fibrosis, causing vasculogenic impotence due to penile outflow dysfunction in the corpora cavernosa. The causes of impotence after surgery alone or after surgery. radiation, and chemotherapy for rectal cancer are complex, and not all answers to the problem reside in autonomic nerve-preservation. Attention to all of the potential causes of impotence and of urinary dysfunction will require continued longitudinal research by clinical investigators from multiple disciplines.

Objective: To review the authors' experience with local excision of early rectal cancers to assess the effectiveness of initial treatment and of salvage surgery., Summary Background Data: Local excision for rectal cancer is appealing for its low morbidity and excellent functional results. However, its use is limited by inability to assess regional lymph nodes and uncertainty of oncologic outcome., Methods: Patients with T1 and T2 adenocarcinomas of the rectum treated by local excision as definitive surgery between 1969 to 1996 at the authors' institution were reviewed. Pathology slides were reviewed. Among 125 assessable patients, 74 were T1 and 51 were T2. Thirty-one patients (25%) were selected to receive adjuvant radiation therapy. Fifteen of these 31 patients received adjuvant radiation in combination with 5-fluorouracil chemotherapy. Median follow-up was 6.7 years. One hundred fifteen patients (92%) were followed until death or for greater than 5 years, and 69 patients (55%) were followed until death or for greater than 10 years. Recurrence was recorded as local, distant, and overall. Survival was disease-specific., Results: Ten-year local recurrence and survival rates were 17% and 74% for T1 rectal cancers and 26% and 72% for T2 cancers. Median time to relapse was 1.4 years (range 0.4-7.0) for local recurrence and 2.5 years (0.8-7.5) for distant recurrence. In patients receiving radiotherapy, local recurrence was delayed (median 2.1 years vs. 1.1 years), but overall rates of local and overall recurrence and survival rates were similar to patients not receiving radiotherapy. Among 26 cancer deaths, 8 (28%) occurred more than 5 years after local excision. On multivariate analysis, no clinical or pathologic features were predictive of local recurrence. Intratumoral vascular invasion was the only significant predictor of survival. Among 34 patients who developed tumor recurrence, the pattern of first clinical recurrence was predominantly local: 50% local only, 18% local and distant, and 32% distant only. Among the 17 patients with isolated local recurrence, 14 underwent salvage resection. Actuarial survival among these surgically salvaged patients was 30% at 6 years after salvage. CONCLUSIONS The long-term risk of recurrence after local excision of T1 and T2 rectal cancers is substantial. Two thirds of patients with tumor recurrence have local failure, implicating inadequate resection in treatment failure. In this study, neither adjuvant radiotherapy nor salvage surgery was reliable in preventing or controlling local recurrence. The postoperative interval to cancer death is as long as 10 years, raising concern that cancer mortality may be higher than is generally appreciated. Additional treatment strategies are needed to improve the outcome of local excision.

Intraoperative irradiation (IORT) refers to the delivery of a single high dose of radiation therapy at the time of surgery when the tumor bed can be precisely defined and adjacent normal tissue maximally protected. It can be effectively delivered using either electrons (IOERT) or photons produced from a high-dose-rate gamma emitting radioisotope (HDR-IORT) and has been explored primarily for locally advanced or recurrent tumors at high risk for local failure despite extensive resection and full dose external beam radiation. With coordinated multidisciplinary interaction, IORT can be integrated in a combined-modality setting without undue additional toxicity. The purpose of this review will be to summarize the growing HDR-IORT experience in the treatment of various cancers, to compare its efficacy and toxicity vis a vis the IOERT data, and to discuss future trials as well as new areas of potential application., (Copyright 2002 by W.B. Saunders Company)

Two decades have passed since the late 1970s, which witnessed the introduction of total mesorectal excision (TME)-based operations for rectal cancers on both sides of the Atlantic. Since the introduction of TME, clinical experience has been reported widely in the form of single- and multisurgeon reports from wide geographic regions with multiple participants, and from specialty services with narrow focus and high levels of expertise. All of these published results conclude that in comparison with conventionally practiced blunt surgery for rectal cancer, TME-based (i.e., anatomically correct, sharply performed) operations are associated with significantly lower rates of pelvic (local) recurrences, a significantly higher rate of survival, and significantly lower long-term morbidity. The latter is accomplished through dramatically higher rates of sphincter preservation, and the preservation of both sexual and urinary functions. Overall, there is a remarkable similarity in the clinical results that have been reported from diverse centers. TME now forms the basis of large randomized clinical trials in which the role of adjuvant therapy is being reexamined. The current status of TME is reviewed, and the authors' clinical results of a consecutive series of 544 TME-based operations performed through 1998 are updated.

In the design of operations for rectal cancers, the focus is often on circumventing the local extent of disease and leaving the pelvis free of cancer. The local extent of disease may range from minimal intramural invasion to the direct extension of a primary tumor to pelvic sidewall structures, e.g., the internal iliac vessels. In the absence of distant spread, understanding the planes of pelvic anatomy may allow the knowledgeable surgeon to cure patients who would otherwise be declared unresectable. We present the four planes (and one rare situation) available for sharp dissection which allow for the resection of all but a few cases of locally advanced disease., (Copyright 2000 Wiley-Liss, Inc.)

Adjuvant chemoradiation therapy following resection of T3N0 rectal cancer is recommended in order to reduce the incidence of local recurrence and improve survival. However, recent experience with rectal cancer resection utilizing sharp dissection and total mesorectal excision has resulted in a reduction in local recurrence rates to as low as 5% without adjuvant treatment. The purpose of this study was to determine if rectal cancer resection utilizing sharp mesorectal excision alone is adequate treatment for local control of T3N0 rectal cancer. Between July 1986 and December 1993, 95 patients with T3N0M0 rectal cancer underwent resection with sharp mesorectal excision and did not receive any adjuvant therapy. Various prognostic factors were analyzed for their association with local recurrence and survival. Seventy-nine patients had a low anterior resection, 10 of whom had a coloanal anastomosis, and 16 had an abdominoperineal resection. The median follow-up was 53.3 months. Six patients had local recurrence, 12 had distant recurrence, and three had local and distant recurrences. The overall local recurrence rate was 9% crude and 12% 5-year actuarial. The overall crude recurrence rate was 22%. The 5-year disease-specific survival rate was 86.6% with an overall survival of 75%. Postoperative complications occurred in 18 patients (19%). Five patients (6%) had a documented anastomotic leak. Perioperative mortality was 3%. No technical factors, including type of resection (low anterior vs. abdominoperineal), location of tumor, or extent of resection margin, were significant for determining local recurrence. The only histopathologic marker significant for determining local recurrence was lymphatic invasion (P <0.04). Sharp mesorectal excision with low anterior resection or abdominoperineal resection for T3N0M0 rectal cancer results in a local recurrence rate of less than 10% without the use of adjuvant therapy. Therefore, in select patients with T3N0M0 rectal cancer, the standard use of adjuvant therapy for local control may not be justified.

Objective: To determine perioperative morbidity, survival, and local failure rates in a large group of consecutive patients with rectal cancer undergoing low anterior resection by multiple surgeons on a specialty service. The primary objective was to assess the surgical complications associated with preoperative radiation sequencing., Summary Background Data: The goals in the treatment of rectal cancer are cure, local control, and preservation of sphincter, sexual, and bladder function. Surgical resection using sharp perimesorectal dissection is important for achieving these goals. The complications and mortality rate of this surgical strategy, particularly in the setting of preoperative chemoradiation, have not been well defined., Methods: There were 1233 patients with primary rectal cancer treated at the authors' cancer center from 1987 to 1995. Of these, 681 underwent low anterior resection and/or coloanal anastomosis for primary rectal cancer. The surgical technique used the principles of sharp perimesorectal excision. Morbidity and mortality rates were compared between patients receiving preoperative chemoradiation (Preop RT, n = 150) and those not receiving preoperative chemoradiation (No Preop RT, n = 531). Recurrence and survival data were determined in patients undergoing curative resection (n = 583, 86%) among three groups of patients: those receiving Preop RT (n = 131), those receiving postoperative chemoradiation (Postop RT, n = 110), and those receiving no radiation therapy (No RT, n = 342)., Results: The perioperative mortality rate was 0.6% (4/681). Postoperative complications occurred in 22% (153/681). The operative time, estimated blood loss, and rate of pelvic abscess formation without associated leak were higher in the Preop RT group than the No Preop RT group. However, the overall complication rate, rate of wound infection, anastomotic leak, and length of hospital stay were no different between Preop RT and No Preop RT patients. With a median follow-up of 45.6 months, the overall actuarial 5-year recurrence rate for patients undergoing curative resection (n = 583) was 19%, with 4% having local recurrence only, 12% having distant recurrence, and 3% having both local and distant recurrence, for an overall local recurrence rate of 7%. The actuarial 5-year overall survival rate was 81%; the disease-free survival rate was 75% and the local recurrence rate was 10%. The overall survival rate was similar between Preop RT (85%), Postop RT (72%), and No RT (83%) patients (p = 0.10), whereas the disease-free survival rate was significantly worse for Postop RT (65%) patients compared with Preop RT (79%) and No RT (77%) patients (p = 0.04)., Conclusion: The use of preoperative chemoradiation results in increased operative time, blood loss, and pelvic abscess formation but does not increase the rate of anastomotic leaks or the length of hospital stay after low anterior resection for rectal cancer. The 5-year actuarial overall survival rate for patients undergoing curative resection exceeded 80%, with a local recurrence rate of 10%.

Aims: Improved local control and survival in the treatment of rectal cancer have been reported after total mesorectal excision and after extended lymphadenectomy. Comparison of published results is difficult because of differences in patient populations and definitions. We compared three series of patients who underwent standardized surgery [i.e. total mesorectal excision (TME) or D3 lymphadenectomy] with patients who underwent conventional surgery, using actual patient data and uniform definitions., Methods: TME was performed at Memorial Sloan-Kettering Cancer Center, New York, USA (n=254) and the North Hampshire Hospital, Basingstoke, UK (n=204). D3 lymphadenectomy was performed at the National Cancer Center, Tokyo (n=233). Conventional surgery was used in hospitals in Norway (n=366) and in hospitals of the Comprehensive Cancer Center West, The Netherlands (n=354). Only patients with a curatively resected primary TNM Stage II or Stage III rectal cancer within 12 cm from the anal verge were included., Results: Five-year overall survival and cancer-specific survival were 62-75% and 75-80%, respectively, in the standardized surgery groups and 42-44% and 52%, respectively, in the conventional surgery groups. Local recurrence rates ranged from 4 to 9% in the standardized surgery groups and 32-35% in the conventional surgery groups., Conclusions: A 30% survival difference and 25% local recurrence difference is not likely to be caused by the shortcomings which are inherent in a non-randomized study: selection bias, assessment variability or stage migration. This study suggests that standardized surgery gives superior survival and local control when compared to conventional surgery., (Copyright 1999 W.B. Saunders Company Ltd.)

Local and distant recurrence rates and disease-free and overall survival are markedly improved by total mesorectal excision, with little increase in morbidity, compared with other techniques of resection of rectal cancer. Adjuvant therapy is associated with significant morbidity and initial results suggest it may not be beneficial in the aggregate. Adjuvant therapy must be re-evaluated in trials using TME as standard operative technique. Different subgroups of patients, defined by clinical and pathological criteria will be best served by different forms of therapy and should be studied based on rates of local and distant recurrence. Selected groups of patients will be best served by undergoing no adjuvant therapy of any kind.

Purpose: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT)., Methods and Materials: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo)., Results: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery., Conclusion: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

We have examined the results of abdominoperineal resection (APR) for primary cancer of the rectum performed in accordance with the principles of total mesorectal excision (TME) and autonomic nerve preservation (ANP). TME is defined as sharp pelvic dissection under direct vision between the parietal and visceral planes of the pelvic fascia. TME results in the resection of all mesorectal disease with intact, negative lateral or circumferential margins of resection. Statistical analysis was done of survival, local recurrence, and both sexual and urinary functions in a prospective database of consecutive patients. Operative mortality was 2% (3/148) due to cardiac disease. Overall survival was 60%, significantly worse than consecutive patients from the same database who were able to undergo sphincter preservation (81%) (p = 0.0003). Poorer survival was statistically related to the presence of positive lymph nodes (p = 0.0009). Overall, local recurrence rates were 5% (8/148) in patients without distant metastases, and 15% to 21% in patients with positive nodes. Positive lymph nodes, N2 disease, lymphatic vascular invasion, and perineural invasion were independent significant risk factors for local recurrence. Sexual function was preserved in approximately 57% of patients undergoing APR versus 85% of patients undergoing sphincter preservation. No significant urinary morbidity was encountered. Low rectal cancer requiring APR seems to be a disease with more locally advanced disease and adverse pathologic features than are seen with mid-rectal cancers treatable by low anterior resection. APR when performed in accordance with the principles of TME and ANP ensures the greatest likelihood of resecting all regional disease while preserving both sexual and urinary functions. Preoperative combined modality treatment may be warranted in all T3 or greater low rectal cancers.

Rectal cancer persists as a significant worldwide problem. Currently, surgery is associated with a poor prognosis, a high likelihood of permanent colostomy and a high rate of local recurrence in patients with regional disease (transmural penetration or involvement of regional mesenteric lymph nodes). Functional changes such as impotence and bladder dysfunction remain distressingly common consequences of conventional surgery. Over the past two decades, a fundamental change in operative technique has taken place. Conventional surgery (which is performed using blunt technique along undefinable tissue planes) has given way to sharp dissection along definable planes. The technique known as total mesorectal excision (TME) or complete circumferential mesorectal excision (CCME) produces the complete resection of an intact package of the rectum and its surrounding mesorectum, enveloped within the visceral pelvic fasia with uninvolved circumferential margins. As a result of TME, 5-year survival figures have risen from 45-50% to 75%, local recurrence rates have declined from 30% to 5-8%, sphincter preservation has risen by at least 20% for mid- and lower rectal cancers, and the rates of impotence and bladder dysfunction have declined from 50-85% to 15% or less. Patients with rectal cancer can now have a good prognosis, and intact image and high quality of life. The integration of multidisciplinary radiation therapy and chemotherapy into the care of patients undergoing TME or CCME for rectal cancer is presently under clinical trial.

Purpose: More than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome., Materials and Methods: Data for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed., Results: The perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predictive of poorer outcome. Sex, age greater than 70 years, site of primary tumor, or perioperative transfusion was not predictive of outcome. By multivariate analysis, positive margin, size greater than 10 cm, disease-free interval less than 12 months, multiple tumors, and extrahepatic disease were independent predictors of poorer outcome. Short disease-free interval or multiple tumors were nevertheless associated with a 5-year survival rate greater than 24%., Conclusion: Liver resection for colorectal metastases is safe and effective therapy and currently represents the only potentially curative therapy for metastatic colorectal cancer. The only absolute contraindication to resection is extrahepatic disease. A randomized trial to examine efficacy of surgical resection cannot ethically be performed. Liver resection should be considered standard therapy for all fit patients with colorectal metastases isolated to the liver.

Purpose: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer., Methods and Materials: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU., Results: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%)., Conclusion: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.

Sphincter-preserving operations represent an important model for integrating the goals of surgery for rectal cancers. These goals--the achievement of cure and local control and the preservation of autonomic visceral pelvic functions--are inherently related. Sphincter-preserving procedures are possible for patients with mid-rectal cancers (6 to 10 cm from the anal verge) and for highly selected patients with distal rectal cancers (< or = 5 cm from the anal verge). Total mesorectal excision, a new concept in resection with negative circumferential margins, dramatically enhances both cure and local control. Total mesorectal excision can be combined with sphincter preservation. Perioperative adjuvant therapy protocols have been combined with sphincter-preserving operations in many investigative settings. Functional outcomes and recent survival data seem to favor preoperative over postoperative radiation therapy. The currently changing standards of surgery for rectal cancer, which result in improved local control, should enhance long-term sphincter preservation in the future.

Objective: Comparison of an aggressive approach (including total mesorectal excision and combined modality adjuvant therapy) with a conventional approach in the treatment of primary rectal cancer., Design: Retrospective study., Setting: Memorial Sloan-Kettering Cancer Centre, New York (MSKCC) and University Hospital Leiden, the Netherlands (UHL)., Subjects: One hundred and sixty-nine patients treated at MSKCC and 96 patients treated at UHL., Interventions: Total mesorectal excision (MSKCC) and conventional resection (UHL)., Main Outcome Measures: Overall survival and local recurrence-free survival., Results: Five-year overall survival was 73% for MSKCC patients and 52% for UHL patients (P < 0.001). Five-year local recurrence-free survival was 83% for MSKCC patients and 72% for UHL patients (P=0.001). Relative risk of dying or developing a local recurrence was 3.37 and 2.61, respectively, for patients treated at UHL compared to patients treated at MSKCC (P<0.001 and P=0.008, respectively)., Conclusions: These data suggest that an aggressive approach including total mesorectal excision and combined modality adjuvant therapy improves survival and local control compared to a conventional approach.

Background: We performed a study to assess sexual and urinary function after total mesorectal excision with autonomic nerve preservation for primary carcinoma of the rectum., Study Design: We studied retrospectively postoperative sexual and urinary function in 136 (78 percent) of 175 eligible patients (82 males and 54 females) who responded to a standardized questionnaire., Results: The ability to engage in intercourse was maintained by 86 percent of the patients younger than 60 years of age, and by 67 percent of patients 60 years and older. Eighty-seven percent of male patients maintained their ability to achieve orgasm. The type of surgery (abdominoperineal resection compared to low anterior resection), and age equal to or greater than 60 years were significantly associated with male sexual dysfunction. Of the female patients, 85 percent were able to experience arousal with vaginal lubrication and 91 percent could achieve orgasm. The majority of patients had few or no complaints related to urinary function. Serious urinary dysfunction such as neurogenic bladder was not encountered., Conclusions: Autonomic nerve preservation in association with total mesorectal excision reduces the operative morbidity rate and is successful in minimizing sexual and urinary dysfunction in the operative treatment of patients with carcinoma of the rectum.

Total mesorectal excision with autonomic nerve preservation for rectal cancer is based on the anatomy of the mesorectum and of the pelvic autonomic nerves. Cadaver dissections were performed to describe the relationship between these structures. Between the rectum and the sacrum a retrorectal space can be developed, lined anteriorly by the visceral leaf and posteriorly by the parietal leaf of the pelvic fascia. The hypogastric nerve runs anterior to the visceral fascia, from the sacral promontory in a laterocaudad direction. The splanchnic sacral nerves originate from the sacral foramina, posterior to the parietal fascia, and run caudad, laterally and anteriorly. After piercing the parietal layer of the pelvic fascia, approximately 4 cm from the midline, the sacral nerves run between a double layer of the visceral part of the pelvic fascia. The relationship between the hypogastric nerves, the splanchnic nerves and the pelvic fascia was comparable in all six specimens examined.

Background: Total mesorectal excision (TME) is reported to reduce local recurrence and improve survival rates in patients with carcinoma of the rectum., Study Design: Two hundred forty-six consecutive patients with Dukes' B (T3, N0, M0) and C (T(any), N1-2, M0) primary rectal carcinomas underwent operation according to the principle of TME. Kaplan-Meier estimates of survival and pelvic recurrence rates were calculated from a database of patients followed prospectively., Results: The operative mortality rate was 0.8 percent (two of 246). The Kaplan-Meier five-year survival rate for patients with stages B and C was 74.2 percent; for patients with stage T3, N0, M0, 86.7 percent; for patients with stage T(any), N1-2, M0, 64.0 percent; and for patients with substage T3, N1-2, M0, 68.0 percent. Pelvic recurrences were observed in a total of 18 patients (7.3 percent) with or without metastases. In the 246 patients with Dukes' stages B and C, pelvic recurrence rates were 4.0 and 8.1 percent, respectively, in the presence or absence of distant metastases, and 3.0 and 5.8 percent, respectively, in the absence of distant spread. Statistically significant risk factors for pelvic recurrence were N2 disease and perineural invasion. Adjuvant radiation therapy was of no statistical benefit in preventing local recurrences., Conclusions: Total mesorectal excision cures carcinoma of the rectum and provides excellent local control through resection of the entire unit of regional spread that is excised, intact and with negative circumferential margins. Total mesorectal excision is compatible with autonomic nerve preservation and with sphincter preservation. The current role of combined modality adjuvant therapy, which is standard therapy following conventional surgery, should be reconsidered in patients who have undergone resection in accordance with TME.

We report the impact of selected clinicopathologic features on local failure and disease-free survival in 22 patients with localized, mobile, primary resectable rectal cancer treated with local excision and postoperative radiation therapy. Full thickness local excisions with negative margins were performed in 21 patients. One patient had a transanal snare excision of a T1 polyp. Postoperatively patients received 4500-4950 cGy (medial 4680 cGy) whole pelvis, and in 15 this was followed by a conedown of 360-1000 cGy (median 360 cGy). Two received 5-FU. Tumors were evaluated for size, gross appearance, distance from the ana verge, T stage, blood vessel invasion, lymphatic vessel invasion, and DNA content (ploidy, DNA index, and proliferation index). The median follow-up was 37 months (range 5-73). With increasing T stage there was a corresponding increase in local failure (T1: 0%, T2: 17%, and T3: 33%) and a decrease in disease-free survival (T1: 100%, T2: 67%, and T3: 50%). When accounting for the effect of T stage, tumors which were either BVI-or ulcerative were associated with an increase in local failure, and tumors which were < or = 3 cm, ulcerative, or nonaneuploid were associated with a decrease in disease-free survival. However, none of the differences reached statistical significance. Although other clinicopathologic features may have an impact, T stage remains the most reliable clinicopathologic feature by which to predict local failure and disease-free survival in patients with rectal cancer who undergo local excision and postoperative radiation therapy.

Last month, the authors presented the principles of high-dose-rate intraoperative radiation therapy (HDR-IORT), a new approach to intraoperative radiation delivery, as well as their criteria for patient selection, the goals of surgery, and their approach to minimizing surgical morbidity. This month, the authors present the technical aspects of delivering HDR intraoperative brachytherapy, their dosimetry atlas, and their results using HDR-IORT in the treatment of patients with colorectal cancer.

Purpose: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer., Methods and Materials: Thirty patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (2: T2 28:T3) involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (range: 1.5-6 cm) and the median distance from the anal verge was 4 cm (range: 3-7 cm). The whole pelvis received 46.8 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 43 months (range: 6-82 months)., Results: Of the 29 patients who underwent resection, 3 (10%) had a complete pathologic response and 24 (83%) were able to successfully undergo a low anterior resection/colonanal anastomosis. The incidence of local failure was crude: 17% and 4-year actuarial: 23%. The 4-year actuarial survival was 75%. One patient developed a partial disruption of the anastomosis and two developed rectal stenosis. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in 22 of the 24 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 77%. The median number of bowel movements/day was two (range: 1-6)., Conclusions: This technique may be an alternative to an abdominoperineal resection in selected patients. Continued follow-up is needed to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection.

Purpose: There is an increasing awareness of local procedures to treat early stage rectal cancer. Abdominoperineal resection (APR) or low anterior resection (LAR) has been recommended if adverse pathologic findings are encountered in the local excision specimen. No data compare the impact on survival of "immediate" resection for adverse features vs. "salvage" resection for clinical recurrence., Methods: We reviewed retrospectively 155 patients who underwent initial curative treatment of invasive rectal cancer by excision (91), snare-cautery (44), and fulguration (20)., Results: Twenty-one patients underwent APR/LAR immediately after initial local treatment, whereas another 21 patients underwent salvage APR/LAR for local recurrence. The disease-free survival after APR/LAR was 94.1 percent for the immediate group and 55.5 percent for the delayed group (P < 0.05)., Conclusion: This decreased survival observed after delayed resection supports the recommendation for immediate APR/LAR when adverse pathologic features are present in the excision specimen.

We report the local control and survival in a previously reported phase I dose escalation trial of combined postoperative 5-FU, high dose leucovorin (LV), and sequential radiation therapy followed by maintenance LV/5-FU for the treatment of patients with clinically resectable rectal cancer. Following surgery for stages T3-4N0-2M0 primary (21) or recurrent (4) rectal cancer, 25 patients received 5-FU/LV x 1 cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of 5-FU/LV was given concurrent with the fourth week of radiation. Patients received an additional 10 cycles of LV/5-FU. The median follow-up was 40 months (range 18-52). The incidence of grade 3+ acute toxicity in the 9 patients who received the recommended dose of 5-FU was 44%. The local failure rate was 28%. Abdominal and distant failure rates were 24%. The 3-year actuarial disease-free survival was 74% and the overall survival was 80%. Our preliminary data reveal reasonable local control and survival rates. However, further follow-up is needed to assess our results at 5 years. Postoperative combined modality therapy with high-dose LV may be an option for the adjuvant treatment of patients with resectable rectal cancer.

Background: Transrectal ultrasonography (TRUS) supplements clinical evaluation of early carcinoma of the rectum in selecting patients for local operative therapy, such as transanal excision (TAE)., Study Design: This study was done to evaluate the accuracy of ultrasonographic staging of tumor depth (T stage) in patients with suspected early carcinoma of the rectum, to compare ultrasonographic with clinical T-staging accuracies within this patient group, to determine if any specific tumor characteristics (configuration, size, location) predispose toward ultrasonographic T-staging inaccuracy, and to examine the role of TRUS in operative selection for patients with early carcinoma of the rectum., Results: Between April 1990 and December 1992, 62 patients with primary carcinoma of the rectum underwent ultrasonographic staging (uT), whereby three uT4, 27 uT3, 24 uT2 and eight uT1 carcinomas were identified. Of the 32 patients with suspected intramural (uT1 or uT2) disease, 27 underwent prompt operative excision or resection at our institution, allowing comparative histopathologic staging. In this highly selected patient subset, uT1 staging was correct in all instances; uT2 staging was incorrect in 45 percent of instances, with 30 percent having unpredicted transmural penetration. Ultrasonographic and clinical staging accuracies were quantitatively similar, and no tumor characteristics were consistently associated with ultrasonographic imprecision., Conclusions: Among patients with clinically suspected early carcinoma of the rectum, the decision to perform TAE is supported by ultrasonographic T1 staging. By contrast, the decision to perform TAE cannot be based solely on ultrasonographic T2 staging, because of the possibility for transmural penetration of tumor.

Purpose: This study was designed to evaluate the spectrum, clinical presentation, management, and outcome of anorectal disease in neutropenic leukemic patients and to compare operative and nonoperative management in neutropenic leukemic patients., Methods: A retrospective review of hospital records was performed., Results: One hundred fifty-one of 2,618 (5.8 percent) patients hospitalized with leukemia had concomitant symptomatic anorectal disease. Data from 81 patients were available for analysis. Fifty-two (64 percent) were treated nonoperatively and 29 (36 percent) underwent operative treatment. Fifty-seven (70.4 percent) had absolute neutrophil counts < 1,000/mm3, and 54 (66.7 percent) were severely neutropenic (absolute neutrophil count < 500/mm3). Management and outcomes of 54 severely neutropenic patients were analyzed. In 20 patients who underwent surgery there were 4 deaths (20 percent) and 4 recurrences (20 percent), whereas in 34 patients managed nonoperatively there were 6 deaths (18 percent) and 4 recurrences (12 percent) (P > 0.05)., Conclusions: Symptomatic anorectal disease afflicted 5.8 percent of hospitalized leukemic patients. In these patients, anorectal sepsis was a major source of mortality. Our data suggest that anorectal abscesses in neutropenic leukemic patients may be safely drained. Because we did not observe excessive morbidity or mortality (20 percent vs. 18 percent) in the operated neutropenic leukemics as compared with the nonoperated patients, selected neutropenic leukemic patients should not be denied anorectal surgery when otherwise indicated.

Purpose: We report the results of 22 patients with localized, mobile, resectable rectal cancer treated with local excision and postoperative radiation therapy., Methods and Materials: Margins were negative in 21 patients and unassessable in 1. The median follow-up was 37 months (range: 5-73 months). The median tumor size was 3.0 cm (range: 1-6.2 cm). Full-thickness local excisions were performed in 21 patients: transanal, 11; transsphincteric, 2; and posterior proctotomy (Kraske), 8. All margins were inked and were microscopically negative in 21. One patient had a transanal snare excision of a T1 polyp. Postoperatively patients received 4,500-4,950 cGy (median: 4,680 cGy) whole pelvis, and in 15 this was followed by a conedown to 360-1,000 cGy (median: 360 cGy)., Results: The 4-year actuarial survival was 79% and the 4-year actuarial colostomy-free survival was 73%. The incidence of local failure was 18% and increased with T stage: T1: 0/4 (0%); T2: 2/12 (17%); and T3: 2/6 (33%). Four patients developed local failure at 6, 10, 15, and 21 months. Of the four, three underwent salvage APR and were locally controlled at 6, 33, and 58 months following salvage surgery. The incidence of abdominal failure was 18% and distant failure was 18%. Of the 15 eligible patients, 14 (93%) had good or excellent sphincter function., Conclusions: The results of local excision and postoperative radiation therapy are encouraging; however, more experience is needed to determine if this approach ultimately has similar local control and survival rates as standard surgery.

Objective: Our institution's experience with low anterior resection in combination with coloanal anastomosis (LAR/CAA) for primary rectal cancer was reviewed (1) to determine cancer treatment results, 2) to identify risk factors for pelvic recurrence, and 3) to assess the long-term success of sphincter preservation., Summary Background Data: Use of sphincter-preserving resection for mid-rectal and selected distal-rectal cancers continues to increase. As surgical techniques and adjuvant therapy evolve, treatment results must be carefully assessed., Methods: One hundred thirty-four patients treated for primary rectal cancer by LAR/CAA between 1977 and 1990 were studied retrospectively. All pathologic slides were reviewed. Median follow-up was 4 years., Results: Actuarial 5-year survival for all patients was 73%. Among 36 patients who relapsed, distant metastatic disease had developed at the time of first clinical relapse in most (86%). Pelvic recurrence was detected in 13 patients, an actuarial rate of 11% at 5 years. Mesenteric implants, positive microscopic resection margin, T3 tumor, perineural invasion, blood vessel invasion, and high tumor grade were associated with increased risk for pelvic recurrence. Eleven patients ultimately required permanent colostomy, and in eight instances the cause was pelvic recurrence., Conclusions: Low anterior resection combined with coloanal anastomosis provides good treatment for mid-rectal cancers and for some distal rectal cancers. Pelvic recurrence is not associated with short distal resection margins but is correlated with the presence of histopathologic markers of aggressive disease in the primary tumor. Long-term preservation of anal sphincter function depends primarily on control of pelvic tumor and can be achieved in more than 90% of patients.

Background: Up to one-third of patients with anal epidermoid cancer will fail initial chemoradiotherapy (CT-RT) or have local recurrence after treatment. This study evaluates the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with salvage abdominoperineal resection (APR) in these patients., Methods: Thirty-eight patients who underwent salvage APR following 5-fluorouracil (5-FU), mitomycin C, and radiotherapy over the past 12 years were analyzed by retrospective review. Survival was calculated by the Kaplan-Meier method and comparisons by log-rank analysis., Results: The indications for APR were recurrent disease after CT-RT in 14 patients and persistent disease in 24 patients. Median follow-up time and survival were 47 and 41 months, respectively. The actuarial 5-year survival was 44%. Twenty-three patients had recurrent disease after APR. Inguinal lymphadenopathy at initial presentation (p < 0.05), fixation of tumor to the pelvic sidewall (p < 0.01), and pathologic involvement of the perirectal fat (p < 0.01) adversely affected survival. Age, gender, initial response to CT-RT, initial stage of the primary tumor, histologic levator muscle involvement, status of perirectal lymph nodes, and extent of lymphadenectomy did not affect survival., Conclusions: Salvage APR can be expected to yield a moderate number of long-term survivors, but the high rate of disseminated failure suggests the need for additional postoperative treatment.

In a survey of patients treated with coloanal anastomosis for rectal cancer, 81 of 90 eligible patients responded to a questionnaire evaluating current anorectal function. Time from operation to assessment ranged from 1.3 to 12.3 years (median: 4.3 years). The median stool frequency was two per day; 22% of patients reported four or more stools per day. In the patients surveyed, fecal continence was complete in 51%, incontinence to gas only in 21%, minor leak in 23%, and significant leak in 5%. Complete evacuation of the neorectum was problematic in 32%. Overall function was excellent in 28%, good in 28%, fair in 32%, and poor in 12%. The impact of treatment variables on functional outcome was assessed by univariate and multivariate analyses. No surgical technique correlated with improved or impaired outcome. Time since surgery (reduced stool frequency) and use of postoperative adjuvant radiotherapy (increased stool frequency, increased difficulty with evacuation) did appear to influence functional outcome. We conclude that the functional results of coloanal anastomosis are good but not optimal. Continued investigation of the effects of surgical technique and adjuvant therapy is warranted.

Background: The encouraging results seen in patients who received postoperative combined modality therapy in the adjuvant setting have prompted increased interest in preoperative combined modality therapy for patients with unresectable rectal cancer. The authors report the local control and survival of a previously reported Phase I dose escalation trial of combined preoperative 5-fluorouracil (5-FU), high-dose leucovorin (LV), and sequential radiation therapy followed by postoperative LV-5 FU for the treatment of patients with unresectable rectal cancer., Methods: Twenty patients (13, primary and 7, recurrent disease) received LV-5-FU for one cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of LV-5-FU was given concurrently with week 4 of radiation. Six patients received intraoperative brachytherapy. Postoperatively, the patients received LV-5-FU. The pathologic complete response rate was 20%, and 89% underwent a complete resection with negative margins., Results: The crude local failure rate was 26%, and the 3-year actuarial local failure rate was 29% (95% confidence interval [CI], +/- 8.94%). The crude abdominal and distant failure rates were 40% and 30%, respectively. The 3-year actuarial disease-free survival was 64% (95% CI, +/- 6.75%), and the overall survival was 69% (95% CI, +/- 7.65%)., Conclusions: These preliminary data revealed encouraging local control and survival rates. Preoperative combined modality therapy is an attractive approach in patients with unresectable rectal cancer.

Purpose: We performed a Phase I trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer., Methods and Materials: Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy, was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7-16 months)., Results: Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153,000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2., Conclusions: Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, we do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate we remain encouraged with this approach.

Impotence due to parasympathetic nerve injury is one of the most feared consequences of operations for treatment of rectal cancer. Sharp dissection along the parietal pelvic fascia where the parasympathetic nerves are located significantly reduces the incidence of pelvic failure. Autonomic nerve-preserving pelvic sidewall dissections, which combined the benefits of en bloc parietal pelvic dissection with nerve preservation, were performed in 42 men who were undergoing sphincter-preserving operations for treatment of rectal cancer. Thirty-three (86.7%) of the 38 evaluable patients have remained potent, and 29 (87.9%) of the 33 patients have normal ejaculation. Deliberate sacrifice of the inferior hypogastric plexus caused only minor sexual dysfunction. Cancer recurred locally in only one patient (with stage D cancer). Autonomic nerve-preserving pelvic sidewall dissection combines the benefits of curative resection and local control with reduced morbidity, and it preserves potency.

This study aims to identify significant predictors of survival in pediatric and adolescent colorectal carcinoma. We retrospectively analyzed our experience with 29 histologically verified cases, of which 20 were resected for cure. Variables analyzed as predictors of survival included: (1) resectability, (2) regional nodal involvement, (3) depth of invasion, (4) grade, and (5) interval from symptom onset to diagnosis. Signet ring or anaplastic lesions were considered high grade. Survival curves were generated on both the overall group and those resected for cure. Multivariate analysis was performed on the overall group. The median age at diagnosis was 19 years (range, 10 to 21). Median follow-up in survivors was 4.7 years. Signet ring tumors occurred in 45% and another 24% were poorly differentiated. Seventy-six percent presented with regional lymph node metastases. The median survival for the overall group was 16 months, whereas that for those undergoing complete resection was 33 months. In patients undergoing resection for cure, grade (P = .005), regional nodal involvement (P = .007), and depth of invasion (P = .03) were significant predictors of outcome in univariate analysis. In the overall group these variables as well as resectability and distant metastases were significant in univariate analysis. In multivariate analysis high-grade lesions and lymph node involvement were highly correlated, as were resectability and metastases. Thus, either variable (but not both) of each pair added information to the multivariate model. In patients resected for cure, positive nodes or high histological grade became the only significant predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS)