Subtotal colectomy for toxic and fulminant colitis in the era of immunosuppressive therapy.

OBJECTIVE: Prolonged use of immunosuppressive medication to avoid surgery is becoming more common in patients with inflammatory bowel disease, with severe or fulminant colitis. The effect of immunosuppression on postoperative outcomes was reviewed. METHOD: Patients undergoing subtotal colectomy (STC) for fulminant or toxic colitis from 1992 to 2006 were studied to define the effect of immunosuppression (IS) on postoperative complications (POCs). Patient characteristics, diagnosis, operative indication, details of surgery, use of IS, and POC's were reviewed and univariate and multivariate analysis was performed. RESULTS: Eighty-nine patients were studied (55 males). Seventy-two (91%) patients had fulminant colitis and 17 (20%) had toxic colitis. The preoperative diagnosis was ulcerative colitis in 74, indeterminate in 10, and Crohn's disease in five patients. Eighty-two (92%) patients were on some form of immunosuppression, and 14 had a perforation at surgery. Thirty-nine (43.8%) patients experienced a POC. There was no operative mortality. Univariate analysis identified perforation (P = 0.048) and length of surgery (P = 0.002) as predictive of POCs, while multivariate analysis failed to identify a predictor of complications. CONCLUSION: There was no association between immunosuppression and postoperative complications. Complications in this setting are a result of the severity of the inflammatory bowel disease.

Predictors of disease-free survival in rectal cancer patients undergoing curative proctectomy.

OBJECTIVE: To identify the factors that affect the disease-free survival (DFS) of rectal cancer patients. METHOD: Patients from an IRB approved rectal cancer database were reviewed (1990-2000). All patients underwent either abdominoperineal resection or low anterior resection using total mesorectal excision with curative intent. Univariate and multivariate analyses were performed to analyse the factors that influenced DFS. RESULTS: A total of 304 patients were reviewed (mean age 64, 52% male). Seventy-seven per cent of patients received neoadjuvant therapy (28.6% short-course radiation therapy (RT), 35.5% long-course RT, 12.5% chemo-RT). The radial margin was involved with tumour in 5.2% of patients (final pathology). The overall survival rate was 85.2% with a mean follow-up time of 33 +/- 26 months. The mean time to death was 34.8 +/- 26.8 months. Local recurrence (+/- distant recurrence) occurred in 4%. Anastomotic leaks occurred in 3.6% of patients. Overall pathologic stage, pathologic T stage, nodal status, the use of adjuvant chemotherapy, tumour fixation, involvement of the radial margin, the presence of mucin, and lymphatic and perineural invasion (PNI) were predictors of DFS by univariate analysis. Of note, anastomotic leaks and obstructing cancers did not influence DFS. Using multivariate analysis with backward elimination, overall pathologic stage, radial margin status, adjuvant chemotherapy, and PNI predicted the DFS. CONCLUSION: Major predictors of DFS in rectal cancer are the overall pathologic stage, adjuvant chemotherapy, radial margin status and PNI. Radial margin status may be a marker of tumour aggressiveness and should be considered in deciding on adjuvant chemotherapy.

Neoadjuvant external beam radiation and proctectomy for adenocarcinoma of the rectum.

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

Radiation therapy for epidermoid carcinoma of the anal canal, clinical and treatment factors associated with outcome.

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

Treatment of rectal adenocarcinoma with endocavitary and external beam radiotherapy: results for 199 patients with localized tumors.

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

A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.

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

Pretreatment clinical findings predict outcome for patients receiving preoperative radiation for rectal cancer.

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

Manometric squeeze pressure difference parallels functional outcome after overlapping sphincter reconstruction.

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

Neoadjuvant therapy for adenocarcinoma of the rectum: tumor response and acute toxicity.

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

Outcome of patients with rectal adenocarcinoma and localized pelvic non-nodal metastatic foci.

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

Usefulness of FDG-PET scan in the assessment of suspected metastatic or recurrent adenocarcinoma of the colon and rectum.

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

Use of endoanal ultrasound in patients with rectovaginal fistulas.

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

Laparoscopic vs. open abdominoperineal resection for cancer.

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

Colorectal cancer: risk factors and recommendations for early detection.

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

A practical approach to familial and hereditary colorectal cancer.

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

Selection criteria for treatment of rectal cancer with combined external and endocavitary radiation.

PURPOSE: The aim of this study was to identify factors predictive of recurrence of rectal tumors treated with combined external and endocavitary radiation. METHODS: Seventy-two patients with rectal cancer were evaluated clinically and with transrectal ultrasound before combined external and endocavitary radiation. Ideal lesions were moderately differentiated, mobile, not ulcerated, <3 cm in diameter, and <12 cm from the anal verge. External radiation (4,500 cGy) was given during five weeks followed by endocavitary radiation (3,000 cGy x 2). Median follow-up was 31 (range, 7-93) months. RESULTS: Pretreatment transrectal ultrasound stages were uT1 (6 patients), uT2 (27 patients), and uT3 (39 patients). Clinical evaluation identified 26 ideal and 46 nonideal tumors. Overall recurrence was 36 percent; mean time to recurrence was 12 months. Ideal lesions recurred less than nonideal (15 vs. 48 percent; P = 0.01). Mobile lesions recurred less than tethered lesions (26 vs. 52 percent; P = 0.048). Transrectal ultrasound stage was predictive of recurrence (0 percent uT1, 22 percent uT2, and 51 percent uT3; P = 0.015). Surgery was possible in 14 of 17 patients with pelvic recurrence only; 11 patients (65 percent) had curative surgery. Distant metastases occurred in nine patients; all had pelvic recurrences, and six died of disease. CONCLUSION: Patients with uT3 or nonideal rectal cancers should not be offered combined external and endocavitary radiation for cure. Transrectal ultrasound stage is the only independent predictor of recurrence.

Proctectomy and coloanal anastomosis for rectal cancer.

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

A specific CpG methylation pattern of the MGMT promoter region associated with reduced MGMT expression in primary colorectal cancers.

The enzyme O6-methylguanine-DNA methyltransferase (MGMT) protects cells from the cytotoxic and mutagenic effects of alkylating agents. Approximately 20% of tumor cell lines lack MGMT activity and are highly sensitive to alkylating agents. In established cancer cell lines, MGMT expression appears to be correlated with methylation of residues in both the promoter and the body of the gene. The effect of methylation of the MGMT promoter on gene expression and carcinogenesis in primary tumors is unknown. We investigated methylation of the MGMT promoter region in primary colorectal cancers and normal colonic mucosa. We used five methylation-sensitive restriction enzymes (BssHII, SacII, Eagl, Nael, and Smal) and Southern blot analysis to assess methylation in 46 cancers and 22 controls. Methylation of Eagl and Nael sites was seen in 12 tumors but in none of the 22 normal colorectal mucosa specimens. This difference was statistically significant (P<0.01). Methylation-sensitive single-nucleotide primer extension analysis of four additional cytosine residues confirmed methylation of the promoter region in the tumors identified by Eagl and Nael digestions and served to further quantitate the extent of methylation. Western blot analysis of 21 tumors revealed statistically significant lower MGMT expression in the eight tumors with methylation of the Eagl and Nael sites and nt -128 than in the 13 tumors lacking the methylation pattern (P<0.05). MGMT activity was lower in tumors with methylation than in tumors that were not methylated. The difference was not, however, statistically significant. We conclude that a subset of colorectal tumors is characterized by a specific methylation pattern in the MGMT promoter associated with reduced MGMT expression.

Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment.

BACKGROUND: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen. METHODS AND MATERIALS: During the period of 1975-1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%). RESULTS: With a post treatment follow-up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery). CONCLUSION: Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.