Richard M. Devine

Curative reoperations for locally recurrent rectal cancer

PURPOSE: Our aims were to determine the morbidity, survival and its influencing factors, and patterns of failure for patients who underwent further surgery with the hope of cure for locally recurrent rectal cancer. METHODS: Between January 1981 and December 1988, 224 patients with a preoperative diagnosis of recurrent rectal cancer underwent additional surgery at Mayo Medical Center in Rochester, Minnesota. Of these, 65 underwent further surgery with the hope of cure,i.e.,no gross/microscopic residual disease at tumor margins after reoperation. Factors assessed included type of original operation, time interval between operation for primary tumor and initial operation for recurrence, symptom status, degree of fixation, types of reoperations for recurrence, and adjuvant therapy. RESULTS: None of the patients died within 30 days of reoperation. Seventeen complications requiring hospitalization and/or surgical procedure were observed in 14 patients. Extended operations (involving partial or complete removal of surrounding organs/structures) required more time to perform, a greater number of transfusions, and a longer hospital stay than more limited operations. Three-year, five-year, and median survival were 57, 34, and 44.7 months, respectively. Survival was greater after curative than after palliative resection (P<0.001). Survival tended to be greater in females (P<0.075) and in patients without pain (P<0.065). Cumulative probability of local failure was 24, 41, and 47 percent at 1, 3, and 5 years, respectively. Cumulative risk of distant metastasis was 30, 51, and 62 percent at 1, 3, and 5 years, respectively. CONCLUSIONS: Our results indicate that complete excision of locally recurrent rectal cancer can provide a significant number of patients with long-term survival and can be accomplished safely in select patients.

Ileal Pouch—anal Anastomosis: Reoperation for Pouch-related Complications

The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients.

Randomized prospective trial comparing ileal pouch-anal anastomosis performed by excising the anal mucosa to ileal pouch-anal anastomosis performed by preserving the anal mucosa.

OBJECTIVE The purpose of the study is to compare the results of ileal pouch-anal anastomosis (IPAA) in patients in whom the anal mucosa is excised by handsewn techniques to those in whom the mucosa is preserved using stapling techniques. SUMMARY BACKGROUND DATA Ileal pouch-anal anastomosis is the operation of choice for patients with chronic ulcerative colitis requiring proctocolectomy. Controversy exists over whether preserving the transitional mucosa of the anal canal improves outcomes. METHODS Forty-one patients (23 men, 18 women) were randomized to either endorectal mucosectomy and handsewn IPAA or to double-stapled IPAA, which spared the anal transition zone. All patients were diverted for 2 to 3 months. Nine patients were excluded. Preoperative functional status was assessed by questionnaire and anal manometry. Twenty-four patients underwent more extensive physiologic evaluation, including scintigraphic anopouch angle studies and pudendel never terminal motor latency a mean of 6 months after surgery. Quality of life similarly was estimated before surgery and after surgery. Univariate analysis using Wilcoxon test was used to assess differences between groups. RESULTS The two groups were identical demographically. Overall outcomes in both groups were good. Thirty-three percent of patients who underwent the handsewn technique and 35% of patients who underwent the double-stapled technique experienced a postoperative complication. Resting anal canal pressures were higher in the patients who underwent the stapled technique, but other physiologic parameters were similar between groups. Night-time fecal incontinence occurred less frequently in the stapled group but not significantly. The number of stools per 24 hours decreased from preoperative values in both groups. After IPAA, quality of life improved promptly in both groups. CONCLUSIONS Stapled IPAA, which preserves the mucosa of the anal transition zone, confers no apparent early advantage in terms of decreased stool frequency or fewer episodes of fecal incontinence compared to handsewn IPAA, which excises the mucosa. Higher resting pressures in the stapled group coupled with a trend toward less night-time incontinence, however, may portend better function in the stapled group over time. Both operations are safe and result in rapid and profound improvement in quality of life.

Locally advanced primary colorectal cancer: intraoperative electron and external beam irradiation +/- 5-FU.

PURPOSE For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) +/- 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT regimens. METHODS AND MATERIALS From April 1981 through August 1995, 61 patients received an IOERT dose of 10-20 Gy, usually combined with 45-55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, < or = microscopic in 39, and unresected in 1. RESULTS Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) and < or = microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), < or = microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with < or = microscopic residual after gross total resection (p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free SR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy--1 of 29 or 3%, > or = 15 Gy--6 of 26 or 23%, p = 0.03). CONCLUSIONS Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatment regimens because the incidence of distant metastases was 50% of patients at risk.

Intraoperative electron and external beam irradiation with or without 5-fluorouracil and maximum surgical resection for previously unirradiated, locally recurrent colorectal cancer

PURPOSE/OBJECTIVE: 1) Disease control and survival will be evaluated for treatment regimens containing intraoperative electron irradiation (IOERT) for locally recurrent, previously unirradiated colorectal cancers. 2) Various prognostic factors will be evaluated to determine whether they have an impact on disease control or survival. MATERIALS AND METHODS: From April 1981 through August 1995, 123 patients with previously unirradiated locally recurrent colorectal cancers received IOERT at our institution, usually as a supplement to external beam irradiation (EBRT) and maximum resection. All received EBRT with or without concomitant 5-fluorouracil-based chemotherapy. Forty-five Gy in 25 fractions was given to the tumor or tumor bed plus 3-cm to 5-cm margins in 121 of 123 patients and a boost of 5.4 to 9 Gy in 3 to 5 fractions to the tumor plus 2-cm margins. Maximum resection was performed before or after EBRT. IOERT doses ranged from 10 to 20 Gy in 119 of 123 patients, with dose dependent on resection margins (130 fields in 123 patients). Maintenance chemotherapy was given to only two patients. RESULTS: Disease relapse and survival were evaluated. Central failure (within the IOERT field) was documented in 13 of 123 patients (11 percent) with a five-year actuarial rate of 26 percent. Local relapse (in EBRT field) occurred in 24 patients (20 percent); five-year rate was 37 percent. Distant metastases occurred in 66 patients (54 percent); five-year rate was 72 percent. Median survival was 28 months, with overall survival at two, three, and five years of 62, 39, and 20 percent, respectively. Tolerance data suggest a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (≤12.5 Gy, 2 of 29 or 7 percent; ≥15 Gy, 19 of 101 or 19 percent;P=0.12). Survival and disease control were analyzed as a function of potential prognostic factors. None of the prognostic factors had a significant impact on disease control or survival. Although there was a trend for reduction in local relapse rates with gross totalvs. partial resection, this neither achieved statistical significance nor translated into improved survival. Patients with gross residual disease after maximum resection had three-year and five-year survival rates of 36 and 18 percent, respectively, which paralleled results for patients with gross total resection at 41 and 24 percent, respectively. CONCLUSION: Encouraging trends for improved local control with or without survival exist in separate locally recurrent colorectal IOERT analyses from our institution and other institutions. Therefore, continued evaluation of IOERT approaches seems warranted. Disease control within the IOERT and external fields is decreased when the surgeon is unable to accomplish a gross total resection. Therefore, it is reasonable to consistently add 5-fluorouracil or other dose modifiers during EBRT and to evaluate the use of dose modifiers in conjunction with IOERT (sensitizers and hyperthermia). In view of high systemic failure rates of >50 percent in patients with locally recurrent disease, more routine use of systemic therapy is indicated as a component of IOERT-containing treatment regimens (use existent chemotherapy and/or develop effective immunotherapy and gene transfer therapy). Even with locally recurrent lesions, the aggressive multimodality approaches including IOERT have resulted in improved local control and long-term survival rates of 20 percentvs. an expected 5 percent with conventional techniques.

Management of Crohn's disease of the ileoanal pouch with infliximab☆

OBJECTIVES:The occurrence of Crohns disease (CD) in a patient with an ileal-pouch anstomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients.METHODS:Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1–16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions.RESULTS:At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3–44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab.CONCLUSIONS:Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.

Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients

PURPOSE Information in the literature regarding salvage treatment for patients with locally recurrent colorectal cancer who have previously been treated with high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective review was therefore performed in our institution to determine disease control, survival, and tolerance in patients treated aggressively with surgical resection and intraoperative electron irradiation (IOERT) +/- additional EBRT and chemotherapy. METHODS AND MATERIALS From 1981 through 1994, 51 previously irradiated patients with recurrent locally advanced colorectal cancer without evidence of distant metastatic disease were treated at Mayo Clinic Rochester with surgical resection and IOERT +/- additional EBRT. An attempt was made to achieve a gross total resection before IOERT if it could be safely accomplished. The median IOERT dose was 20 Gy (range, 10--30 Gy). Thirty-seven patients received additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4 Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil +/- leucovorin during EBRT. Three patients received additional cycles of 5-fluorouracil +/- leucovorin as maintenance chemotherapy. RESULTS Thirty males and 21 females with a median age of 55 years (range 31--73 years) were treated. Thirty-four patients have died; the median follow-up in surviving patients is 21 months. The median, 2-yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%, respectively. The 2-yr actuarial central control (within IOERT field) is 72%. Local control at 2 years has been maintained in 60% of patients. There is a trend toward improved local control in patients who received > or =30 Gy EBRT in addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr local control rates of 81% vs. 54%. Distant metastatic disease has developed in 25 patients, and the actuarial rate of distant progression at 2 and 4 years is 56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4 severe). Ureteral narrowing or obstruction occurred in seven patients. All but one patient with neuropathy or ureter fibrosis received IOERT doses > or =20 Gy. CONCLUSION Long-term local control can be obtained in a substantial proportion of patients with aggressive combined modality therapy, but long-term survival is poor due to the high rate of distant metastasis. Re-irradiation with EBRT in addition to IOERT appears to improve local control. Strategies to improve survival in these poor-risk patients may include the more routine use of conventional systemic chemotherapy or the addition of novel systemic therapies.

Outcome of "Indeterminant" Colitis Following Ileal Pouch-Anal Anastomosis

To establish whether patients with indeterminant colitis (patients with ulcerative colitis whose surgical specimens also show features of Crohns colitis) have an adverse outcome after ileal pouch-anal anastomosis (IPAA), the authors reviewed the pathologic reports and postoperative status of 514 consecutive patients who underwent IPAA for chronic ulcerative colitis (CUC). Twenty-five patients (5 percent) had features of indeterminant colitis (IC), including unusual distribution of inflammation, deep linear ulcers, neural proliferation, transmural inflammation, fissures, creeping fat, and retention of gobletcell population. The clinical and functional outcome of these 25 IC patients was compared with that of the remaining 489 CUC patients. The mean follow-up was 38±18 months. No significant differences in complication rates, pouch function, incidence of “pouchitis,” or requirement for pouch excision were detected in the two groups at follow-up. Although the authors are continuing to perform IPAA on patients with IC, a better definition of the IC patient and a more objective, prospective analysis of outcome of IC following IPAA is required before confident and specific treatment policies can be recommended.

Anatomy of radical prostatectomy as defined by magnetic resonance imaging.

PURPOSE We examined and defined anatomical structures relevant to radical prostatectomy using magnetic resonance imaging. MATERIALS AND METHODS Before radical prostatectomy, 15 men underwent high-resolution magnetic resonance imaging studies of their pelvic floors (fast spin echo, T2 weighting of 3- to 4-mm. contiguous or overlapping slices) in axial, coronal, and sagittal planes. RESULTS Pubovesical ligaments, rather than the commonly reported puboprostatic ligaments, were observed attaching the bladder-prostate unit to the pubis. We suggest that the part of the urethra that extends from the apex of the prostate to the bulb of the penis, which is surrounded by the striated sphincter, should be termed the sphincteric urethra rather than the membranous urethra. Further, we found no evidence that supports the traditional concept of a urogenital diaphragm. The lower part of the striated urethral sphincter was flanked on its sides by the anterior recesses of the ischioanal fossae. The portion of the levator ani, which we have termed the puboanalis sling, flanked the apex of the prostate. The most anteromedial portion of this sling inserts into the perineal body and should be termed the puboperinealis. The terminal part of the gastrointestinal tract (the part continued beyond the levator ani) should be termed the anal canal, not the rectum, as used frequently in the urologic literature. Therefore, the initial plane of dissection in radical perineal prostatectomy passes along the anterior portion of the anal canal, not the rectum. CONCLUSION We used magnetic resonance imaging to study male pelvic floor and perineal anatomy without the artifact of dissection. This study allowed us to devise a more precise nomenclature with respect to radical prostatectomy and, in so doing, to provide a better understanding of both the retropubic and the perineal operations.

Home Parenteral Nutrition—A 3-Year Analysis of Clinical and Laboratory Monitoring

We report a 3-year analysis (1986 to 1989) of the management of 63 home parenteral nutrition patients, 40 with short-bowel syndrome and 23 with chronic intestinal obstruction with or without intestinal resection. Intravenous fluid requirements varied from 0.9 to 6 L/day, and the content of glucose varied between 46 and 531 g/day, protein varied from .0 to 85 g/day, fat from .0 to 100 g/day, sodium from 37 to 695 mEq/day, potassium from 30 to 220 mEq/day, chloride from 60 to 760 mEq/day, and acetate from 0 to 200 mEq/day. Body weight was normalized and well maintained in the majority of patients, but using the strict definition of deficiency as the presence of one abnormal value during 3 years, more than half had abnormal plasma chloride, glucose, alkaline phosphatase, serum glutamic oxaloacetic transaminase, total protein, albumin, selenium, and iron concentrations, and more than a third had low calcium, magnesium, vitamin D, and vitamin C levels. Normochromic anemia was seen in 73% and high blood creatinine associated with low urine volumes in 42%. Most (78%) returned to relatively normal lifestyles, but employability was occasionally impaired by loss of third-party insurance coverage resulting from a therapy that may cost