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BACKGROUND The incidence of rectal cancer in patients ≤ 50 years of age is increasing. The response to neoadjuvant treatment in patients ≤ 50 years of age is not known. Factors affecting the response to neoadjuvant therapy in this age group have not been evaluated. OBJECTIVE This study aims to evaluate the rate and identify factors that affect pathologic response to neoadjuvant therapy in patients with early age-of-onset rectal cancer. DESIGN This study is a retrospective review. SETTING The investigation was conducted at a tertiary-care cancer referral center. PATIENTS Included were 193 consecutive patients ≤ 50 years of age with rectal cancer who underwent neoadjuvant therapy followed by surgical resection. INTERVENTIONS No interventions were performed. MAIN OUTCOME MEASURES The primary outcome measured was the pathologic response to neoadjuvant treatment. RESULTS The median age was 44 years, and 34% of the patients were female. The median distance from the anal verge was 7 cm. The median percentage of lumen occupied by tumor was 50%. The median CEA level was 3.5 ng/mL. The median treatment response was 80%. The mean number of lymph nodes examined was 15 per patient. Twenty-two percent of patients had a complete or near-complete (≥ 95%) response to neoadjuvant treatment. Seventy-seven percent of evaluable patients experienced tumor or lymph node downstaging on pathologic examination. The presence of adverse histologic features, percentage of lumen occupied by tumor, and CEA level differed between those with

Background We have previously demonstrated the prognostic significance of rectal cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other cancers have reported that hypoxia influences response to neoadjuvant chemoradiation. Objective This study aimed to 1) characterize hypoxia-related protein expression in locally advanced rectal cancer before neoadjuvant chemoradiation, 2) determine the comodulation of hypoxia-related protein expression, and 3) evaluate the relationship between hypoxia-related protein expression and overall survival, time to recurrence, and tumor regression grade. Design Immunohistochemical analysis of 4 hypoxia-related proteins (HIF-1α, CA-IX, VEGF, and GLUT-1) was performed on archival pretreatment rectal cancer biopsies. Patients : Eighty-five patients with locally advanced rectal cancer treated with neoadjuvant radiation and 5-fluorouracil-based chemotherapy were included. Main outcome measures The impact of hypoxia-related protein expression on outcome was evaluated by use of Cox proportional hazards model. Hypoxia-related protein expression was correlated with tumor regression grade by use of Spearman correlation coefficients. Results Median follow-up was 54 months. CA-IX expression was associated with overall survival (p = 0.01). HIF-1α expression was weakly correlated with VEGF (r = 0.26, p = 0.02) and GLUT-1 (r = 0.35, p = 0.001). Hypoxia-related protein expression was not associated with time to recurrence or Mandard tumor regression grade. Conclusions Elevated CA-IX expression may be associated with poorer overall survival in locally advanced rectal cancer treated by neoadjuvant chemoradiation and resection. The expression of the hypoxia-related proteins HIF-1α, VEGF, and GLUT-1 may be comodulated in locally advanced rectal cancer. Further studies are needed to evaluate the mechanisms governing hypoxia regulation and the role of hypoxia in rectal cancer response to neoadjuvant chemoradiation.

At present, pelvic phased array-coil MR is used as the validated imaging modality for measurement of the closest predicted radial mesorectal margin for rectal cancer. Endorectal ultrasound is also used to assess the clinical stage of the cancer that will determine the recommendation for neoadjuvant chemoradiation, but it has not been used to assess the closest predicted radial margin.We propose to assess endorectal ultrasound identification of mesorectal margins and the measurement of the closest predicted radial tumor-mesorectal margin.Patients included were those having MRI and endorectal ultrasound for evaluation of primary rectal cancer in 2010 at a tertiary cancer referral colorectal clinic. Clinical data, MRI, and endorectal ultrasound images were assessed. Two independent retrospective measurements of mesorectal dimensions were correlated to evaluate the reproducibility of identifying mesorectal margins. MRI and endorectal ultrasound images were compared for independent measurements of mesorectal dimensions and of the closest predicted radial mesorectal margin. MRI and endorectal ultrasound determination of margin involvement were assessed for agreement.Fifty-two patients were studied with an average rectal cancer distance to the anal verge of 6.8 cm. Interobserver correlation coefficients of endorectal ultrasound mesorectal dimensions ranged from 0.47 to 0.53 (p0.01). MR and endorectal ultrasound measurements of the closest predicted radial mesorectal margin were correlated r = 0.56 (p0.0001). MR and endorectal ultrasound determination of margin involvement agreed in 81% of cases.Endorectal ultrasound has substantial agreement with MR to measure the closest predicted radial tumor-mesorectal margin. Correlations between observers and modalities for identification of mesorectal dimensions are modest. Further assessment is indicated to confirm endorectal ultrasound mesorectal measurements in a larger sample and to understand the advantages and disadvantages relative to MR.

Negative surgical margins are important for local control of rectal cancer treated with sphincter-preserving surgery. However, the association of rectal cancer recurrence with close distal margin is not well established.Data were extracted from a prospective database of patients collected between 1991 and 2003. Included were 627 patients who underwent curative low anterior resection with total mesorectal excision for rectal cancer 2 to 12 cm from the anal verge. Three hundred ninety-nine patients received neoadjuvant therapy, 65 received postoperative adjuvant therapy alone, and 163 were treated with surgery alone. Median follow-up was 5.8 years.On multivariable analysis, overall recurrence was associated with pathologic stage, lymphovascular invasion, and distal margin. Mucosal recurrence was uncommon; only 16 events were recorded, and of those only 8 were at the initial site of isolated tumor recurrence; 7 of the 8 were surgically salvaged. On univariable analysis, mucosal recurrence was associated with close distal margin (5 vs 2% at 5 y) and lymphovascular invasion (7 vs 2%). Pelvic recurrence, other than isolated mucosal recurrence, was associated with distal location (6 vs 4% at 5 y) and lymphovascular invasion (11 vs 4%). Distal margin as a continuous variable was associated with overall recurrence (excluding isolated mucosal recurrence).Close distal resection margin identifies patients with increased risk of mucosal and overall cancer recurrence. Although neither causality nor a minimally acceptable margin length can be defined, the data support the importance of achieving a clear distal resection margin in the surgical management of rectal cancer.

PURPOSE: A clinical complete response to neoadjuvant therapy occurs in a subset of patients with rectal cancer. Management of these patients is controversial and tension exists between the recurrence risk with observation, and the impact of surgery on quality-of-life. Therefore, the objective was to develop a decision-analytic model to evaluate the relative benefits of surgery vs. observation in rectal cancer patients who achieve clinical complete response after neoadjuvant chemoradiation. METHODS: Clinically relevant inputs and events, including the ability to identify complete responders, likelihood of relapse and of salvage surgery after relapse, and utilities for each health state, were simulated by use of a Markov state-transition model. Transition probabilities and health-state utilities were derived from the literature and expert consensus. One-way and two-way sensitivity analyses were performed to assess the robustness of model results to assumptions. The primary outcome was quality-adjusted life expectancy. RESULTS: In the base-case analysis, the quality-adjusted life expectancy with surgery exceeded observation (5.63 vs. 5.34 quality-adjusted life-years). Sensitivity analysis demonstrated that observation was preferred to surgery if the ability to correctly identify patients with true complete responses exceeded 58 percent, if quality-of-life after surgery was poor (utility

Successful selection of patients with rectal cancer for local excision requires accurate preoperative lymph node staging. Although endorectal ultrasound is capable of detecting locally advanced disease, its ability to correctly identify nodal metastases in early rectal lesions is less well described. This study examines the accuracy of endorectal ultrasound in determining nodal stage based on depth of penetration of the primary lesion (T stage). Between 1998 and 2003, endorectal ultrasound was performed on 938 consecutive patients; 134 had biopsy-proven rectal cancers and were treated with radical resection, without neoadjuvant therapy. Lymph node metastases were measured pathologically and correlated with endorectal ultrasound and clinicopathologic features. Accuracy and specificity of endorectal ultrasound nodal staging was determined. The overall accuracy of endorectal ultrasound nodal staging for the study cohort was 70 percent, with a 16 percent false-positive rate and 14 percent false-negative rate. Endorectal ultrasound was more likely to overlook small metastatic lymph node deposits. The size of lymph node metastasis and accuracy of endorectal ultrasound nodal staging was related to T stage. The specificity of endorectal ultrasound nodal staging, or the ability to identify patients who were node-negative, was dependent on T stage. Early rectal lesions are more likely to have lymph node micrometastases not detected by endorectal ultrasound. The ability of endorectal ultrasound to correctly identify patients without lymph node metastasis is dependent on the T stage of the primary lesion. The limitations of endorectal ultrasound in accurately staging nodal disease in early rectal lesions may, in part, explain the relatively high recurrence rates seen after local excision.

This study was designed to evaluate one institution’s experience with treatment outcomes for rectal squamous-cell carcinoma. Using our prospective Colorectal Database, we identified patients diagnosed with rectal squamous-cell carcinoma at our institution between 1983 and 2005. Pathology was rereviewed, tumor immunophenotype was compared to control cases of anal squamous-cell carcinoma and rectal adenocarcinoma, treatment modalities and outcomes were analyzed. Twelve patients were identified (10 females median age, 58 years). Median distal extent of tumors was 7 (range, 5–8) cm from the anal verge. Treatment included chemotherapy only (n = 1), chemoradiation only (n = 2), induction chemotherapy followed by chemoradiation and surgery (n = 2), chemoradiation followed by surgery (n = 5), and surgery followed by chemoradiation (n = 2). The chemotherapy regimen was 5-fluorouracil-based. Radiotherapy total dose was 50.4 Gy (1.8 Gy/day, daily × 5) external iliac and inguinal nodes were not included in the radiation field. Complete clinical responders to chemoradiation (n = 2) received no further treatment. All seven partial responders underwent surgery; six had complete pathologic response; nodal status in two of six was unknown because they had local excision. Immunophenotypical analysis showed similar keratin expression profile between rectal squamous-cell carcinoma (n = 5) and rectal adenocarcinoma (n = 5), which is different from anal squamous-cell carcinoma (n = 10). All patients were alive without evidence of disease at follow-up (median follow-up, 2.6 (range, 0.5–16) years). Our data suggest that most patients treated with upfront chemoradiation therapy followed by surgery did well. Sphincter-preserving surgery is usually feasible. Clinical judgment of tumor response after chemoradiation is not completely reliable. Immunohistochemistry suggests a common cellular origin for rectal squamous-cell carcinoma and rectal adenocarcinoma, which is different from anal squamous-cell carcinoma.

Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients.We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy.With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1-6.2; P = 0.02), preoperative carcinoembryonic antigen5 ng/ml (HR, 2.1; 95 percent CI, 1.1-4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1-4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients withor = 2 poor prognostic features was 57 percent.Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials.

The incidence of anal canal squamous-cell carcinoma is increasing. Limited data exist on predictors of treatment failure. This study was designed to identify predictors for relapse/persistence after first-line therapy. Using one database, we identified 131 Stages I-III patients treated for primary anal canal squamous-cell carcinoma at our institution from December 1986 to August 2006, with minimum six-month follow-up. Demographic, pathologic, treatment, and outcome data were extracted. Treatment failure was defined as biopsy-proven persistence or relapse (local and/or distant). Univariate, bivariate, and multivariate survival analyses were performed. Of 131 patients (median age, 58.3 years; median follow-up, 2.9 (range, 0.6–11.2) years), 66 percent were females, 43.5 percent were Stage II, and 11 (8 percent) were HIV-positive. Surgery only (local excision) was uncommon (6.9 percent, n = 9). One hundred twenty-two patients (93.1 percent) received radiotherapy; two required preradiotherapy diversion. Although 114 (93.4 percent) completed radiotherapy, most required treatment breaks, making total duration of radiotherapy longer than planned. Almost all patients undergoing radiotherapy (96.7 percent, 118/122) also had chemotherapy: 118 (100 percent, Stages I-III) had concurrent chemotherapy: (98 (83.8 percent) mitomycin/5-fluorouracil, 12 (10.2 percent) cisplatin/5-fluorouracil, 8 (6.8 percent) 5-fluorouracil alone); 35 of 46 (76 percent) Stage III patients received induction chemotherapy (34 (97.1 percent) cisplatin/5-fluorouracil, 1 (2.8 percent) 5-fluorouracil alone). Many (44 percent Stages I/II, 48.9 percent Stage III) required dose adjustments. Thirty-seven patients (28.2 percent) failed first-line therapy. There were no differences between patients with relapse (n = 22) or persistence (n = 15) of disease. Bivariate analyses demonstrated that T stage (P = 0.0019), completion of radiotherapy, and total radiotherapy dose (P = 0.03) were all significantly associated with treatment failure. On multivariate analyses, disease stage (P = 0.05) and completion of radiotherapy (P = 0.01) remained significant predictors of relapse-free survival. Tolerance of chemoradiation seems to be an important predictor of treatment success. Effective therapies with less acute toxicity must be identified.

Composite sacropelvic resection for locally advanced recurrent rectal cancer is a high-risk procedure that benefits select patients. We reviewed our recent institutional experience to evaluate case selection, morbidity, and outcomes. Between 1987 and 2004, 29 patients underwent composite resection for recurrent locoregional rectal cancer (17 females; median age, 60 years). Clinicopathologic indicators were evaluated as indicators of survival by log-rank test and Cox proportional hazards model. Of 29 total patients, 27 (93 percent) received radiotherapy with their previous surgery (n = 10; 34 percent) or before sacrectomy (n = 17; 59 percent), and 12 (41 percent) received intraoperative therapy. Sacral resections were performed at S2/S3 (55 percent) or S4/S5 (45 percent) using anterior (41 percent) or combined anterior-posterior approach (59 percent), with adherence to (62 percent) or cortical invasion in (38 percent) the sacrum. A majority of those who had undergone previous abdominoperineal resection had total exenteration (9/13), whereas most patients who had undergone a previous sphincter-preserving procedure had abdominoperineal resection (12/16) and none had exenteration. Pedicle flaps (omental, 11; abdominal rectus, 7) often were used. A median of five (range, 1–33) units of blood was given intraoperatively. Transfusions were associated with previous abdominoperineal resection (P < 0.03), correlating strongly with postoperative morbidity (P < 0.02). There were 33 complications in 17 (59 percent) patients, most commonly perineal wound breakdown (9 (31 percent)) and pelvic abscess (5 (17 percent)). Median hospital stay was 18 (range, 7–56) days, significantly longer in patients with previous abdominoperineal resection (P < 0.02) or postoperative morbidity (P < 0.03). The only postoperative death was from pelvic sepsis. Resection was complete (R0) in 18 patients (62 percent), with microscopically positive margins (R1) in 10 (34 percent) and grossly positive margins (R2) in 1 (3 percent). Two-year and five-year recurrence rates were 47 and 85 percent, respectively; disease-specific survival was 63 and 20 percent, respectively. Less transfusion (P = 0.03), R0 resection (P = 0.005), lack of anterior organ involvement (P = 0.02), and absence of cortical bone invasion (P < 0.001) were associated with better survival on univariate analysis; original colorectal cancer stage was not. Sacrectomy for rectal cancer is a high-risk procedure that can achieve clear resection margins with low mortality in select patients. This procedure has a low cure rate but may provide local disease control with acceptable morbidity.

Desmoid tumors are a clinical problem in 12 to 15 percent of patients with familial adenomatous polyposis. There is no predictably effective treatment for intra-abdominal desmoid tumors, which sometimes cause significant complications by their effects on the ureters or bowel. The relative rarity and the clinical heterogeneity of intra-abdominal desmoid tumors make randomized studies difficult to do. In this article a staging system is proposed to make multi-institutional studies easier. Intra-abdominal desmoid tumors can be staged according to their size, clinical presentation and growth pattern. A way of staging intra-abdominal desmoid tumors is proposed to facilitate stratification by disease severity during collaborative studies of various treatments.

This study examines surgical salvage of locally recurrent rectal cancer following transanal excision of early tumors. Through retrospective review of a colorectal database we identified 50 patients who underwent attempted surgical salvage for local recurrence following initial transanal excision of T1 or T2 rectal cancer. Eight patients had resectable synchronous distant disease. Clinicopathologic variables were associated with extent of surgery required for salvage and outcome. Salvage procedures included abdominoperineal resection (31), low anterior resection (11), total pelvic exenteration (4), and transanal excision (3). One patient had unresectable disease at exploration, requiring diverting ostomy. Of the 49 patients who underwent successful salvage, 27 (55 percent) required an extended pelvic dissection with en bloc resection of one or more of the following structures: pelvic sidewall and autonomic nerves (18); coccyx or portion of sacrum (6); prostate (5); seminal vesicle (5); bladder (4); portion of the vagina (3); ureter (2); ovary (1); and uterus (1). Complete pathologic resection (R0) was accomplished in 47 of 49 patients. Of the eight patients with distant and local recurrence, two underwent synchronous resection and six had delayed metastasectomy. With a median follow-up of 33 months, 29 patients had recurred or died of disease at the time of this analysis. Five-year disease-specific survival was 53 percent. Factors predictive of survival included evidence of any mucosal recurrence on endoscopy, low presalvage carcinoembryonic antigen, and absence of poor pathologic features (lymphovascular and perineural invasion). Patients who required an extended pelvic resection had a worse survival rate. Pelvic recurrence following transanal excision of early rectal cancer is often locally advanced, requiring an extended pelvic dissection with en bloc resection of adjacent pelvic organs to achieve salvage. The long-term outcome in patients undergoing resection is less than expected, considering the early stage of their initial disease. When contemplating local excision for early rectal cancer, the risk of local recurrence, the extent and morbidity of surgery required for salvage, and the modest cure rate following salvage should be considered.

This study was designed to identify preoperative and intraoperative features of locally recurrent colorectal cancer that predict R0 resection in patients scheduled for attempted complete resection followed by intraoperative radiation therapy. Review of a prospective data base identified 119 patients brought to the intraoperative radiation therapy suite for planned complete resection of locally recurrent rectal (n = 101) and colon (n = 18) cancer between January 1994 and November 2000. R0 resection was achieved in 61 patients. This group was compared with patients in which an R1 (n = 38), R2 (n = 7), or palliative procedure (n = 13) was performed. Variables evaluated included: tumor location, features of the primary tumor, and preoperative findings on computed tomography, magnetic resonance imaging, and history/physical. Tumor location was established by review of operative/pathologic reports and classified as axial (anastomotic/perineal), anterior (bladder/genitourinary organs), posterior (presacral), or lateral (pelvic sidewall). When recurrence was confined to the axial location only, or axial and anterior locations, R0 resection was achieved significantly more often than when other locations were involved (P < 0.001, P = 0.003, respectively). When a lateral component was present, R0 resection was achieved significantly less often than when there was no lateral component (P = 0.002). For patients with available preoperative computed tomography and/or magnetic resonance imaging results (n = 70), the finding of lateral tumor involvement was associated with R0 resection significantly less often than when lateral disease was not identified (P = 0.004). Pelvic recurrences confined to the axial location, or axial and anterior locations, are more likely to be completely resectable (R0) than those involving the pelvic sidewall. Efforts to enhance preoperative identification and imaging of these patients are clearly justified.

PURPOSE: This study was designed to review experience with neuroendocrine carcinomas of the colon and rectum at a single institution, with emphasis on the pathology and clinical characteristics of this uncommon malignancy. METHODS: A study group of patients was identified from a prospective colorectal service database. Pathology was reviewed and neuroendocrine tumors were classified by a single pathologist. Medical records were retrospectively reviewed. RESULTS: From March 1975 to September 1998, 38 patients with neuroendocrine carcinomas were identified from the colorectal service database comprising 6495 patients (0.6 percent). These neuroendocrine carcinomas did not include carcinoid tumors. Average patient age was 57 years (range, 29–86 years). There were 17 males (44.7 percent) and 21 females (55.3 percent). Tumors were located as follows: 17 colon, 14 rectum, 6 anal canal, and 1 appendix. The diagnosis of neuroendocrine carcinoma was suggested preoperatively from tissue biopsy in 59.3 percent (16/27) of patients evaluable. Pathology was reviewed and tumors were categorized as small cell carcinoma (n = 22) or large cell neuroendocrine carcinoma (n = 16). Most tumors (20/25 evaluable, 80 percent) stained positive by means of immunohistochemistry for neuroendocrine markers, including chromogranin (18/19), synaptophysin (10/15), and/or neuron-specific enolase (14/15). Metastatic disease was detected at the time of diagnosis in 69.4 percent of the patients (25/36). Tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer (AJCC) Stage I (n = 6), Stage III (n = 7), and Stage IV (n = 25) tumors. As a group, these tumors had a poor prognosis, with a median survival of 10.4 months. One-year, two-year, and three-year survival was 46 percent, 26 percent, and 13 percent, respectively. There was no significant difference in survival based on pathologic subtypes. Median follow-up time was 9.4 months (range, 0.6–263.7 months). CONCLUSIONS: Neuroendocrine carcinomas of the colon and rectum are uncommon, comprising less than 1 percent of colon and rectal cancers. Pathologically, these tumors are poorly differentiated carcinomas with distinctive cytoarchitectural features and are often immunoreactive for markers of neuroendocrine differentiation. The prognosis for highgrade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.

Total pelvic exenteration is performed infrequently in selected patients with locally advanced or recurrent colorectal cancer. We reviewed our contemporary experience with pelvic exenteration for colorectal cancer to identify selection criteria and prognostic factors for longterm survival. METHODS: Between 1991 and 2000, 55 patients (males, 29; median age, 62 years) undergoing total pelvic exenteration for colorectal cancer were identified from a prospective database. Clinicopathologic variables were evaluated as prognostic indicators of long-term survival by log-rank test and multivariate Cox regression. RESULTS: Indications for surgery were recurrent colorectal cancer in 71 percent and primary colorectal cancer in 29 percent. Of 39 patients with recurrent colorectal cancer, 85 percent had previous radiotherapy, and 64 percent had previous abdominoperineal resection. At the time of pelvic exenteration, 49 percent of patients received intraoperative radiation, and 20 percent required sacrectomy. Complete resection with negative margins was achieved in 73 percent. Perioperative mortality after pelvic exenteration was 5.5 percent, and complications included perineal wound infection (40 percent), pelvic abscess (20 percent), abdominal wound infection (18 percent), and cardiopulmonary events (18 percent). Median disease-specific survival for all patients was 48.9 (range, 3.2-105.6) months. Univariate analysis identified five factors associated with decreased survival: male gender, recurrent colorectal cancer, previous abdominoperineal resection, positive surgical margin, and administration of intraoperative radiation. On multivariate analysis, only previous abdominoperineal resection was an independent predictor of unfavorable outcome (P < 0.04). CONCLUSIONS: Total pelvic exenteration can be performed safely in highly selected patients with colorectal cancer and can result in significantly prolonged survival. Less satisfactory outcomes are observed in patients whose indication for pelvic exenteration is recurrent colorectal cancer after abdominoperineal resection.

PURPOSE: Preoperative radiotherapy for rectal cancer avoids radiation to the reconstructed rectum and may circumvent the detrimental effects on bowel function associated with postoperative radiotherapy. We compared the long-term functional results of patients who received preoperative radiotherapy, postoperative radiotherapy, or no radiotherapy in conjunction with low anterior resection and coloanal anastomosis to assess the impact of pelvic radiation on anorectal function. METHODS: One hundred nine patients treated by low anterior resection and straight coloanal anastomosis for rectal cancer between 1986 and 1997 were assessed with a standardized questionnaire at two to eight years after resection. All radiotherapy was given to a total dose of 4,500 to 5,400 cGy with conventional doses and techniques. Most patients received concurrent 5-fluorouracil–based chemotherapy. RESULTS: There were 39 patients in the preoperative radiotherapy group, 11 patients in the postoperative radiotherapy group, and 59 patients in the no radiotherapy group. The postoperative radiotherapy group reported a significantly greater number of bowel movements per 24-hour period (P < 0.01) and significantly more episodes of clustered bowel movements (P < 0.02) than either the preoperative radiotherapy group or the no radiotherapy group. No significant difference in anal continence or satisfaction with bowel function was found among the three groups. CONCLUSION: In this study of straight (nonreservoir) coloanal anastomoses, postoperative pelvic radiotherapy had significant adverse effects on anorectal function, with higher rates of clustering and frequency of defecation than with preoperative radiotherapy. No differences in continence rates were demonstrated, perhaps because of the sample size of the compared groups. We attribute the adverse effects of postoperative radiotherapy to irradiation of the neorectum, which is spared when treatment is given preoperatively. The deleterious effects of adjuvant radiation on long-term anorectal function can be reduced by preoperative treatment.

PURPOSE: Extramammary Paget’s disease of the perianal region is a rare finding that often results in delayed diagnosis and treatment. Although the natural history of the disease is not well characterized, it historically has been associated with other cancers. This study summarizes the history and treatment of all patients diagnosed with perianal Paget’s disease at a single institution. METHODS: Charts of all patients with a diagnosis of extramammary Paget’s disease of the perianal region confirmed or treated at Memorial Sloan-Kettering Cancer Center between 1950 and 2000 were reviewed. Patients with vulvar Paget’s disease or Bowen’s disease were excluded except when Paget’s disease of the perianal region was diagnosed first. Whenever possible, follow-up information was updated. Estimates of overall and disease-free survival were made by the method of Kaplan and Meier. RESULTS: Twenty-seven patients with a median age of 63 years were diagnosed with perianal Paget’s disease. Most patients (74 percent) were treated with wide excision. Local recurrence occurred in 37 percent of all patients treated and in 30 percent of patients (6/20) undergoing a wide excision as part of their treatment. An invasive component was identified in 44 percent of patients (12/27) with perianal Paget’s disease. Six patients (22 percent) required a colostomy as part of the treatment for their disease. Adjuvant chemoradiotherapy was used in 22 percent of patients (6/27) who had more aggressive disease. At a median follow-up of 67 months, 56 percent (15/27) had no evidence of disease, and two patients had died of metastatic disease. The overall and disease-free survival at five years was 59 and 64 percent, respectively, which decreased to 33 and 39 percent, respectively, by ten years. CONCLUSIONS: Perianal Paget’s disease is a rare finding even at a large referral center. The disease process is generally a prolonged one marked by frequent recurrences, and the treatment of first choice is wide excision. Patients with invasive malignancies require more extensive surgery. The role of chemoradiotherapy remains undefined in this disease.

PURPOSE: Isolated locoregional disease accounts for approximately 20 percent of recurrences after treatment for colorectal cancer. It has been suggested that complete resection of these recurrences can result in increased survival. The value of surgery for isolated retroperitoneal recurrences has not been well defined. We have sought to characterize outcome and survival in patients undergoing resection for isolated retroperitoneal recurrences of colorectal cancer. METHODS: From a prospective database, 25 patients were identified as having undergone surgical exploration with curative intent for isolated retroperitoneal recurrences of colorectal cancer between 1988 and 1999. Variables studied included age, gender, location and size of the tumor, extent of resection, disease-free interval, and morbidity and mortality. Statistical analyses were performed using the log-rank test and Kaplan-Meier estimates, with overall survival as the primary end point. RESULTS: The study population consisted of 25 patients (13 males), with a median age of 55 years and a median follow-up of 29 (range, 1–151) months. The median time to first retroperitoneal recurrence was 23 (range, 3–72) months. Twenty patients underwent resection, whereas five patients were deemed unresectable at the time of operation. The median survival in patients who underwent resection patients was 31 months compared with 3 months in those patients who did not undergo resection (P = 0.0001). Analysis of the entire group demonstrated a disease-free interval of greater than 24 months to be a positive predictor of outcome (median survival, 30 vs. 48 months; P = 0.02). For patients undergoing resection, the presence of positive margins (P = 0.01) and tumor size ≥5 cm (P = 0.008) predicted a worse prognosis. In patients who underwent resection, the two-year and five-year overall survival rates were 60 and 15 percent, respectively. CONCLUSIONS: Patients with isolated retroperitoneal recurrences of colorectal cancer generally have a poor prognosis. However, a longer disease-free interval, complete negative-margin resection, and smaller tumor size are associated with long-term survival in selected patients.

PURPOSE: This study was designed to determine predictors of survival after surgery and intraoperative radiotherapy for recurrent rectal cancer. METHODS: From a prospective database, 634 patients undergoing resection for recurrent rectal cancer between January 1990 and June 2000 were identified. Of these, 111 received intraoperative radiotherapy with curative intent, and 100 were available for follow-up. Clinicopathologic variables from both the primary and recurrent operations were evaluated as predictors of disease-free and disease-specific survival by multivariate Cox regression and log-rank test. RESULTS: There were 54 males and 46 females, with a median age of 57 (range, 37-83) years. With a median follow-up of 23.2 months, 60 patients (60 percent) recurred: 20 (33 percent) locally, 27 (45 percent) distantly, and 13 (22 percent) at both sites. Of all variables analyzed, only complete resection with microscopically negative margins and the absence of vascular invasion in the recurrent specimen predicted improved disease-free and disease-specific survival (P < 0.01 for all). Median disease-free survival and median disease-specific survival were 31.2 and 66.1 months, respectively, for complete resection compared with 7.9 and 22.8 months for resection with microscopic or grossly positive margins (P < 0.01 for both). Median disease-free survival and median disease-specific survival were 6.4 and 16.1 months, respectively, in the presence of vascular invasion in the recurrent specimen compared with 23.3 and 57.3 months in the absence of vascular invasion (P < 0.01 and P < 0.05, respectively). Complete resection and the absence of vascular invasion were the only predictors of improved local control as well (P < 0.05 and P < 0.01, respectively). CONCLUSION: Resection with negative microscopic margins and absence of vascular invasion are independent predictors of local control and improved survival after resection and intraoperative radiotherapy for recurrent rectal cancer.

PURPOSE: Familial adenomatous polyposis is a well-described, autosomal dominant, inherited syndrome characterized by diffuse polyposis of the colon and rectum as well as various upper gastrointestinal and extraintestinal manifestations. A subset of patients present with fewer colorectal polyps, later age of onset of polyps and cancer, and a predilection toward involvement of the proximal colon. This variant of familial adenomatous polyposis is known as attenuated familial adenomatous polyposis. The purpose of this review is to summarize current knowledge regarding this poorly understood entity and propose guidelines for diagnosis, surveillance, and surgical management. METHODS: The MEDLINE database was searched from 1985 onward using the keywords, “attenuated familial adenomatous polyposis,” “AFAP,” “adenomatous polyposis coli gene,” and “APC gene.” Additional articles were identified through the reference sections of retrieved papers. All papers that pertained to attenuated familial adenomatous polyposis or mutations in the APC gene producing an attenuated phenotype were included. RESULTS: Attenuated familial adenomatous polyposis is transmitted in an autosomal dominant fashion. Several distinct mutations within the APC gene have been associated with an attenuated phenotype, but variability of disease expression within kindreds possessing identical mutations makes classification difficult. Polyps are diagnosed at a mean age of 44 years, with cancer diagnosed at a mean of 56 years of age. Frequent involvement of the proximal colon necessitates the use of colonoscopy for surveillance, and infrequent involvement of the rectum supports the role of a total abdominal colectomy and ileorectal anastomosis. CONCLUSIONS: Although currently recognized as a distinct clinical entity, attenuated familial adenomatous polyposis may be part of a spectrum of disease that includes familial adenomatous polyposis and is caused by different mutations within the APC gene. Because of its unique characteristics, yet apparent overlap with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, increased awareness of attenuated familial adenomatous polyposis should improve diagnosis, surveillance, and treatment strategies in this unique subset of familial polyposis syndromes.

PURPOSE: Locally advanced primary and recurrent rectal cancers treated with external beam radiation therapy, intraoperative radiation therapy, and chemotherapy represent a complex group of patients in the setting of extensive pelvic surgery and sphincter preservation. We sought to define functional outcome and quality of life in this subset of patients. METHODS: We retrospectively reviewed our experience with locally advanced primary and recurrent rectal cancer patients who underwent intraoperative radiation therapy with either low anterior resection (n=12) or coloanal anastomosis (n=6) between 1991 and 1998. Current functional outcome and quality of life were evaluated by a detailed questionnaire. RESULTS: Median time from operation to assessment was 24 (range, 6–93) months. Using a standardized Sphincter Function Scale, incorporating the number of bowel movements per day and degree of incontinence, patients were graded as poor, fair, good, or excellent function. Of all patients, 56 percent reported unfavorable (poor or fair) function. Of the subset of patients with coloanal anastomosis or very low low anterior resection, 88 percent had unfavorable function as compared with 30 percent with standard low anterior resection. (P=0.02; Fisher's exact probability test). A quality-of-life satisfaction score based on social, professional, and recreational restrictions demonstrated 56 percent of patients to be dissatisfied with their bowel function. CONCLUSIONS: The majority of patients with advanced rectal cancers who require external beam radiation therapy, extensive pelvic surgery, and intraoperative radiation therapy report unfavorable functional and quality-of-life outcomes after sphincter preservation. In this setting patients being considered for coloanal anastomosis or very low anterior resection may be better served by permanent diversion.

PURPOSE: Disease recurrence in the abdominal wall from a primary colorectal cancer is a poorly studied and little understood phenomenon that has received renewed attention after the recognition of port site metastases in patients after laparoscopic colorectal resections. The purpose of the present study was to define the clinical, pathologic, and management issues in patients with abdominal wall metastases from colorectal cancer. METHODS: Patients presenting to Memorial Sloan-Kettering Cancer Center with a diagnosis of colorectal cancer were entered into a prospective database beginning in 1986. Review of this database showed that 31 patients presenting with recurrent disease in the abdominal wall were managed surgically at the institution between 1986 and 1998. RESULTS: A total of 31 patients (19 males) with a median age of 67 (range, 45–86) years presented with recurrent disease between 7 and 183 (median, 24) months after primary surgery. Primary tumors were located in the right colon in 17 patients, left colon in 2 patients, sigmoid colon in 7 patients, and rectum in 3 patients. Nineteen percent of primary tumors were perforated, 45 percent were poorly differentiated, 92 percent were transmural (T3 or T4), and 51 percent had lymph node metastases at presentation. Twenty-two patients presented with a symptomatic abdominal wall mass, whereas recurrence in the abdominal wall was found incidentally in 9 patients undergoing laparotomy. Four patients had isolated abdominal wall disease, whereas the remaining 27 were found to have associated intra-abdominal disease. Six patients who were left with residual intra-abdominal cancer after abdominal wall resection had a median survival time of four months. Twenty-five patients underwent a histologically complete resection of recurrence restricted to the abdominal wall alone (n=4; median survival time, 18 months), abdominal wall and in continuity resection of adherent viscera (n=15; median survival time, 12.5 months), or resection of abdominal wall and intra-abdominal recurrence at a distant site (n=6; median survival time, 22 months, although only 1 patient remained alive with disease). The actual two-year and five-year disease-free survival rates were 16 and 3 percent, respectively. CONCLUSION: Abdominal wall metastases are often indicators of recurrent intra-abdominal cancer; however, aggressive resection in patients with disease restricted to the abdominal wall and associated adherent viscera can result in local disease control with little morbidity and no mortality.

PURPOSE: Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem. Erythromycin, a safe, inexpensive drug that stimulates intestinal motilin receptors, has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery. We aimed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer. METHODS: Between May 1998 and April 1999, 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospective, randomized, placebo-controlled trial. One hundred thirty-four patients completed the study. Patients were excluded if they had extensive metastatic disease, were taking medications known to interact with erythromycin, or if they required an ileostomy. Patients received either 200 mg of intravenous erythromycin or placebo every six hours. Clinical endpoints were recorded and continuous endpoints are presented as mean ± standard deviation. RESULTS: There were no significant complications related to erythromycin. The erythromycin (n=65) and placebo (n=69) groups were comparable regarding demographic and operative factors. The erythromycin group had a slightly shorter length of time to passage of flatus (4.1 ± 1.3vs. 4.4 ± 1.1 days;P=0.03). There was no significant difference between erythromycin and placebo in time to first solid food (5.6 ± 1.9vs. 5.4 ± 1.8 days), time to first bowel movement (5.2 ± 1.9vs. 5.4 ± 1.3 days), or time to discharge from hospital (7.5 ± 2.0vs. 7.6 ± 2.8 days). There was no difference in the rate of clinically significant nausea (26vs. 26 percent;P=0.99), vomiting (17vs. 16 percent;P=0.88), or nasogastric tube placement (9vs. 7 percent;P=0.68). CONCLUSIONS: Erythromycin does not seem to alter clinically important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer.

PURPOSE: The aim of this study was to determine the outcome of patients with leiomyosarcoma of the rectum or anus treated with local excision and brachytherapy. METHODS: Eight patients with leiomyosarcoma of the rectum (7 patients) or anus (1 patient) were treated with a transanal excision followed by a temporary iridium-192 interstitial implant to 4,500 cGy. Median tumor size was 4.2 (range, 1.5–5) cm. Margins were positive in six patients, negative in one patient, and close in one patient. RESULTS: With a median follow-up of 53 months, median survival time was 53 months and the three-year actuarial survival rate was 71 percent. The cumulative incidence of failure as a component of failure for local was 25 percent (2/8), for abdominal was 0 percent (0/8), and for distant was 25 percent (2/8). Four patients eligible for functional analysis all had excellent sphincter function (1–2 bowel movements per day, no soilage). CONCLUSION: In selected patients the use of conservative surgery followed by brachytherapy is a reasonable alternative to an abdominoperineal resection. However, more experience and longer follow-up are needed before this approach can be recommended routinely.

At the beginning of the century, rectal cancer was a deadly disease treated simply by perineal excision. With advances in pathologic staging, preoperative assessment, surgical technique, and CMT made in the last century, we have witnessed improved oncologic and functional results after treatment of rectal cancer. As we look to the future, the use of molecular markers may help identify patients with node-negative disease yet aggressive biology in need of adjuvant therapy. It is also anticipated that improvements in various imaging modalities may better select patients for local procedures or preoperative adjuvant therapy. Further-more, ongoing progress in our understanding of pelvic anatomy and neurophysiology should improve preservation of both genitourinary and sphincter function.

Although sporadic colorectal cancer (CRC) is relatively uncommon in the young, it may constitute an elevated genetic risk for CRC in these individuals. PURPOSE: This study was designed to determine extent of colorectal cancer in families of probands under 40 years of age. METHODS: Medical records of all consecutive patients, 40 years of age or younger at the time of CRC surgery, during the time period 1986 to 1994 were examined. Cases of familial adenomatous polyposis and ulcerative colitis were excluded.Viainterviews of surviving probands or nearest relatives, dates of birth and death, causes of death, and diagnosis of cancer were recorded on all first-degree relatives (parents, siblings, and offspring), second-degree relatives (grandparents, aunts, and uncles), and any other relatives. RESULTS: A total of 128 patients, 40 years of age or less at time of CRC resection, were identified. Of these, 45 probands/families were reached by phone, and 45 detailed family histories were obtained. Age range of these 45 probands was 19 to 40 (mean, 33.1) years. In 25 families there was no history of CRC in first-degree, second-degree, or third-degree relatives. Eight of 45 probands (17.8 percent) had at least one first-degree relative with CRC, and three of these eight families fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer (HNPCC). In all three families, inheritance of CRC appeared to segregate with the maternal side of the family. In addition, 5 of 43 non-HNPCC probands had at least one first-degree, second-degree, or third-degree relative less than 40 years of age, at time of CRC diagnosis. CONCLUSION: Ascertainment of a detailed family history in early age of onset CRC patients identifies frequent familial clustering of CRC and HNPCC in 17.8 percent of cases.

This study was designed to determine if p53 nuclear overexpression, as detected by immunohistochemistry, is a marker of prognostic significance in early (Stage I) colorectal cancer (CRC).Tissue sections obtained from archival blocks of 66 patients with surgically treated Stage 1 CRC were stained immunohistochemically for p53 using a monoclonal antibody (PAB 1801-Ab2). Differences in survival between p53 positive (p53+) and p53 negative (p53-) groups were compared using Kaplan-Meier survival curves and the log-rank test.Thirty-four patients (51.5 percent) were p53+ and 32 (48.5 percent) were p53-. There were significantly more p53+ tumors in females (23 of 34) compared with males (11 of 34) (P = 0.01). Follow-up ranged from 1 to 128.5 (mean, 44.7; median, 38.2) months. Thirteen patients (19.7 percent) developed recurrence, of whom five died of disease. Univariate analysis of clinical and pathologic variables did not reveal my statistically significant differences between p53+ and p53- tumors. Mean actuarial survival was longer (48.2 months) in the p53- group compared with the p53+ group (41.5 months). However, comparison of survival curves using the log-rank test did not show a statistically significant difference in survival (log-rank chi-squared = 0.2; P = 0.6).p53 nuclear overexpression does not appear to be an independent marker of prognostic significance in surgically treated early CRC. Females were more likely to have p53+ tumors. The biologic significance of this findings is unknown.