Gerald Marks

Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers

PURPOSEnTo evaluate the prognostic significance of postchemoradiation pathologic stage and implications for further therapy following preoperative chemoradiation and surgery for advanced/recurrent rectal cancer.nnnMETHODS AND MATERIALSnSeventy-seven patients with advanced (fixed or tethered T4) or recurrent rectal cancer were treated with preoperative chemoradation followed by surgical resection of disease. Chemotherapy consisted of either of bolus 5-FU 500 mg/m(2) per day or continuous venous infusion 225 mg/m(2) per day for the duration of radiation. Radiation therapy was planned to be delivered to the whole pelvis to a dose of 45 Gy followed by a boost to the area of the tumor of 5-15 Gy. Total radiation doses ranged from 40 to 63 Gy with a median of 55.8 Gy. Surgical resection was then carried out 6-10 weeks following the completion of treatment (median, 7 weeks). Twenty-eight patients underwent abdominoperineal resection and and 49 patients had sphincter-sparing surgical procedures. None of the patients received postoperative chemotherapy. Follow-up in these patients ranges from 1 year to 8 years with a median of 3 years.nnnRESULTSnSignificant downstaging of disease was observed with 12/77 (16%) having no residual disease(pT0) and 13% (10/77) found to have pT1-2, N0 disease, 31% (24/77) with pT3-4, N0 and 40% (31/77) for pT0-4, N1-2 cancers. Survival by pathologic stage was 100% for pT0-2, N0 cancers, 80% for pT3-4, N0 and 73% for pTx, N1-2. Local recurrence of disease was observed in 0% of patients with pT0-2, N0 as compared with 13% (3/24) in pT3-4, N0 and 16% (5/31) in pT0-4, N1-2 patients.nnnCONCLUSIONnDownstaging following preoperative chemoradiation is a significant prognostic factor. Patients with pT0, T1, or T2 disease have an excellent prognosis and are unlikely to fail locally or with systemic disease. However, patient with T3/T4 or N+ disease may benefit from further adjuvant chemotherapy.

Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response

PURPOSEnPreoperative chemoradiation is being utilized extensively in the treatment of rectal cancer. However, a variety of dose time factors in both delivery of chemotherapy and irradiation remain to be established. This study was undertaken to examine the impact of dose time factors on pathological complete response (pCR) rates following preoperative chemoradiation for fixed rectal cancer.nnnMETHODS AND MATERIALSnThirty-three patients with fixed rectal cancers were treated with combined 5-fluorouracil (5-FU) chemotherapy and pelvic radiation. Twenty-one patients received bolus 5-FU during the first 3-5 days of radiation and repeated on days 28-33 of their radiation treatment. Twelve patients were treated with continuous infusion (CI) 5-FU, 225 mg/m(2) for the duration of the pelvic radiation. Fifteen patients received a planned total radiation dose of 45 to 50 Gy and 18 patients received a dose of 55 to 60 Gy. Surgical resection was then carried out 6-8 weeks after completion of treatment.nnnRESULTSnDiarrhea was the most frequent acute toxicity. Grade 3 diarrhea was observed in 6 patients requiring treatment interruption and was not related to the chemotherapy regimen. There was no Grade 4 or 5 toxicity. pCR was observed in 2 of 21 (10%) patients treated with bolus 5-FU as compared to 8 of 12 (67%) for patients treated with CI (p = 0.002). pCR were observed in 8 of 18 (44%) patients receiving radiation dose > or = 5500 cGy as compared to 2 of 15 (13%) patients treated to a dose < or = 5000 cGy (p = 0.05). In the high-dose radiation (> or = 5500 cGy) group, a significant difference in pCR rate was observed in patients treated with CI, 8 of 12 (67%) (p = 0.017) as compared with bolus 5-FU (0 of 6). There was no significant difference in operative morbidity or in wound healing between patients treated with bolus 5-FU or CI or within the groups treated with low or high doses of radiation. Three patients have developed local recurrence at 14 and 24 months, two in the low-dose group treated with bolus 5-FU and one patient in the CVI group. The overall 5-year survival for the whole group is 71%.nnnCONCLUSIONnDose intensity of 5-FU and dose of radiation correlate significantly with the likelihood of achieving a pCR. Continuous infusion 5-FU (CI) and a preoperative radiation dose of 5500 cGy or higher can achieve pCR rates of approximately 50%, even in fixed cancers of the rectum.

Sigmoidoscopic examinations with rigid and flexible fiberoptic sigmoidoscopes in the surgeon's office: A comparative prospective study of effectiveness in 1,012 cases

SummaryThe results obtained from 1,012 examinations in an on-going, cooperative study indicate that the overall yield provided by use of the flexible fiberoptic sigmoidoscope is 3.2 times greater than that of examinations with the rigid sigmoidoscope. More than twice (2.4 times) the number of polyps and more than three times the number of cancers were detected with the flexible fiberoptic sigmoidoscope. Experienced endoscopists can perform an examinaton with the flexible fiberoptic sigmoidoscope expeditiously in the office with minimal patient preparation, a high level of patient and physician acceptance, and relative safety when the usual mandatory colonoscopic precautions and guidelines are obeyed. The extraordinary advantages demonstrated by this study warrant wide clinical application of the flexible fiberoptic sigmoidoscope. We strongly recommend provision be made for appropriate training of physicians in the use of the instrument.

High-dose preoperative radiation and full-thickness local excision. A new option for patients with select cancers of the rectum.

Faced with the responsibility of treating patients with invasive distal rectal cancer who were medically unacceptable for the indicated radical surgery, a prospective study was initiated in which high dose preoperative radiation and full-thickness local excision were used. High dose preoperative radiation permitted full-thickness local excision of select cancers, which, by conventional standards, otherwise would have required radical surgery and permanent colostomy. Feasibility was measured on the basis of safety of the technique, control of the cancer, and the quality of anal sphincter function expected. Patients were selected initially because of their predicted inability to tolerate radical surgery, but indications were broadened to include those whose tumors had completely disappeared after irradiation. From 1984 to 1988, 20 patients underwent 21 operative procedures for cancers located between 0 and 7 cm from the anorectal ring. This report is concerned with the 14 patients of this group who were observed for a minimum of 24 months. High-dose preoperative radiation was administered for a total dose of 4500 cGy. Excision and repair were performed 4 to 6 weeks after completion of radiation therapy. Full-thickness disc or hemicircumferential excision was accomplished by transanal, transsphincteric, and transsacral techniques, which included, in several instances, excision of the sphincter mechanism and perineal body, and/or the vaginal wall. Full-thickness local excision after high-dose radiation therapy for rectal cancers has never been reported. Follow-up observation ranged from 24 to 48 months with a median of 31 months. Rectal reservoir function and sphincter control were good in 13 patients. Local recurrence developed in three patients (21 percent), two of whom had postradiation therapy B2 mucinous cancers. Three-year actuarial rate of local recurrence is 23 percent. One (7 percent) patient died of recurrent disease. Actuarial Kaplan-Meier survival at 3 years is 61 percent. Based on the results of this small, select patient group, high-dose radiation therapy followed by full-thickness local excision appears to be a reasonable option for patients who cannot tolerate radical surgery. This bimodal approach also may serve as an option for those who aregoodmedical risks, but for whom sphincter preservation is at stake, and to whom radical surgery offers limited benefits.

Laparoscopic transanal abdominal transanal resection with sphincter preservation for rectal cancer in the distal 3 cm of the rectum after neoadjuvant therapy.

BackgroundThis study reports the short- and long-term results for a prospective rectal cancer management program using laparoscopic radical transanal abdominal transanal proctosigmoidectomy with coloanal anastomosis (TATA) after neoadjuvant therapy.MethodsA prospective database included 102 rectal cancer patients treated with laparoscopic TATA from 1998 to 2008. Patients with distant metastasis at presentation, patients with a tumor more than 3xa0cm from the anorectal ring, and patients not undergoing neoadjuvant therapy were excluded, leaving 79 patients (54 men and 25 women) with a mean age of 59.2xa0years (range, 22–85xa0years) for this study. 13 patients completed neoadjuvant therapy before the original evaluation, and they are excluded from the report of initial clinical assessment. Before treatment, 50 patients were staged as T3 and 16 patients as T2. The mean level in the rectum superior to the anorectal ring was 1.2xa0cm (range, −0.5 to 3xa0cm). In terms of fixity, 31 of the tumors were mobile, 27 were tethered, and 8 showed early fixation. Ulceration was absent in 8 cases, minimal in 12 cases, superficial in 7 cases, moderate in 22 cases, and deep in 17 cases. The mean pretreatment tumor size tumor was 4.8xa0cm (range, 1.5–12xa0cm). The median external beam radiation was 5,400xa0cGy (range, 3,000–8,040xa0cGy), and 77 patients underwent chemotherapy.ResultsThe mean follow-up period was 34.2xa0months (range, 1.9–113.9xa0months). There were no perioperative mortalities. The conversion rate was 2.5%, and the mean largest incision length was 4.3xa0cm (range, 1.2–21xa0cm). For 84% of the patients, the incision was less than 6.0xa0cm, and 46% of the patients had no abdominal incision for delivery of the specimen. The mean estimated blood loss was 367xa0ml (range, 75–2,200xa0ml). All the patients had a temporary diverting stoma. The major morbidity rate was 11%, and the minor morbidity rate was 19%. The major complications included four full-thickness rectal prolapses with repair, one ischemic neorectum with successful reanastomosis, two bowel obstructions, and two failed anastomoses requiring stoma. The ypT stages included 22 complete responses, 12 cases of ypT1, 22 cases of ypT2, 23 cases of ypT3; 65 cases of ypN0, and 14 cases of ypNxa0+xa0(T3xa0=xa07, T2xa0=xa04, T1xa0=xa03). The local recurrence rate was 2.5% (2/79), and the distant metastases rate was 10.1% (8/79). The KM5YAS rate was 97%. Overall, 90% of the patients lived without a stoma. Neorectal loss was due to positive margins or recurrence and was followed by abdominoperineal resection in three cases and ischemia in two cases. The condition of two patients was not reversed due to comorbidities, and one patient had a stoma secondary to bowel obstruction.ConclusionThe study results indicate excellent local recurrence (2.7%) and 5-year survival rates without the need for permanent colostomy in patients with cancers in the distal one-third of the rectum. Laparoscopic total mesorectal excision (TME) with the TATA approach is safe and can be performed laparoscopically. Multi-institutional studies are required to establish the reproducibility of this promising approach.

The reality of radical sphincter preservation surgery for cancer of the distal 3 cm of rectum following high-dose radiation☆

PURPOSEnThe inordinately high rate of locoregional recurrence following sphincter-preserving surgery for cancer of the distal rectum led to the conviction that restorative surgery was inappropriate for the low level cancer. A rectal cancer management program initiated in 1976 that selectively uses high-dose preoperative radiation and sphincter-preserving surgery produced lower than expected local recurrence rates. Exploring the safety of extending the indication for sphincter-sparing surgery to include post-radiation mobile cancers as low as the 0.5 cm level is the purpose of this report.nnnMETHODS AND MATERIALSnOf 218 rectal cancer patients treated with high-dose preoperative radiation and sphincter-preserving procedures, 69 had radical curative surgery for cancers at or below the 3 cm level. Data regarding the first 52 patients whose ages ranged from 39 to 77 years form the basis of this report. Fifty-seven percent were men. Twenty-five (48%) patients had post-radiation unfavorable cancers (B2, C1, C2). Forty-five to sixty Gy high energy photon radiation was administered over 4 1/2 to 6 weeks followed by a similar interval prior to radical proctosigmoidectomy with anastomosis in the distal 1 cm of rectum. Temporary fecal diversion was performed in all patients; colostomies were closed after 8 weeks.nnnRESULTSnThere was zero mortality and two self-limiting anastomotic leaks. Local recurrence developed in 6/43 (14%) patients followed for 24 months or longer. By stage, there were 0/21 (0%) recurrences among O, A, B1 tumors; 6/22 (27%) among unfavorable tumors. By distal margins 1/9 (11%) occurred in .3-1 cm; 4/13 (31%) 1.1-2 cm; 1/18 (5%) 2.1-3 cm. Five-year Kaplan Meier actuarial survival for the 52 patients was 85%.nnnCONCLUSIONnOur data indicates that sphincter preservation can be accomplished in cancers of the distal 3 cm of rectum if high-dose preoperative radiation is administered and fixed cancers are excluded. This is the first reported study of sphincter-preserving surgery for the distal rectal cancer after high-dose radiation. The data are important to the design of new treatment options.

Redefining contraindications to laparoscopic colorectal resection for high-risk patients

BackgroundPatients with major comorbidities often are denied laparoscopic colorectal resections because they are thought to be at too “high risk.” Paradoxically, these patients generally have the most to gain from a minimally invasive surgical approach. This study aimed to examine the feasibility and safety of laparoscopic colorectal resection to determine whether it is contraindicated for “high-risk” patients.MethodsFrom August 1996 to February 2004, 368 consecutive patients (95 men) undergoing a laparoscopic colorectal procedure by a single surgeon were prospectively studied with regard to pre-, peri-, and postoperative events. High-risk patients (nxa0=xa0190) were defined as elderly (age, >80xa0years; nxa0=xa028), morbidly obese (body mass index [BMI], >30xa0kg/m2; nxa0=xa055), American Society of Anesthesiology (ASA) 3 or 4 (nxa0=xa0130), and recipients of preoperative radiotherapy (nxa0=xa054). Multiple risk factors were found for 67 patients, 7 of whom had three risk factors. The median age of the patients was 66xa0years (range, 19–92xa0years). The diagnoses included rectal cancer (nxa0=xa048), diverticulitis (nxa0=xa043), colon cancer (nxa0=xa034), benign polyp (nxa0=xa026), and other (nxa0=xa039). The following procedures were performed: colon resection (nxa0=xa0114; left, 63; right, 41; total abdominal colectomy, 10), rectal resection (low anterior resection or pouch) (nxa0=xa049), coloanal anastomosis (nxa0=xa023), and other (nxa0=xa04). Data regarding intent to treat, operative events, morbidity, mortality, and outcomes were analyzed and form the basis of this report.ResultsNo mortalities occurred. The major morbidity rate was 2%. There were no anastomotic leaks. The cases were laparoscopically performed (94%) or laparoscopically assisted, or were converted to open procedure (3%). The median estimated blood loss was 200xa0ml, and only 5% required perioperative transfusion. The perioperative course involved the following median periods: 2xa0days until flatus, 3xa0days until bowel movement, 1 day until clear liquid diet, 3xa0days until a regular diet, and 5xa0days until hospital discharge.ConclusionIn experienced hands, laparoscopic colorectal resection can be performed safely for “high-risk” surgical patients. The better than expected outcomes in this patient population reinforce the benefits of minimally invasive surgery for this patient group and argues against using parameters of increased age, morbid obesity, high ASA class, or preoperative radiation alone as contraindications to even complex laparoscopic colorectal procedures.

Preoperative radiation therapy and sphincter preservation by the combined abdominotranssacral technique for selected rectal cancers

In an attempt to reduce the incidence of local recurrence and maintain normal sphincteric function in selected patients treated for rectal cancer, a clinical experience using full dose preoperative radiation therapy and a combined abdominotranssacral technique was begun in 1976. The first 24 of 55 patients treated have now been followed for 20 to 84 months, the median follow-up period being 39 months; sufficient data related to their clinical courses are available for analysis. Cancers were selected on the basis of unfavorability and location in the rectum (3- and 7-cm levels). Clinical staging of the disease was accurate and allowed selection and treatment of only those cancers considered unfavorable (stages B2 and C), thereby avoiding unnecessary radiation of more favorable tumors. One anastomotic disruption required reconstruction, but perioperative complications were otherwise unremarkable. Local recurrence in this group of highly unfavorable cancers has not been observed. Normal anal sphincteric function has been preserved in each instance. Preliminary results indicate that full dose preoperative radiation therapy for selected unfavorable and low level cancers permits safe and effective sphincter preservation surgery by the combined abdominotranssacral technique. When proper precautionary measures are observed, surgery can be conducted with the expectation of normal continence and significant reduction in local recurrence.

The fatal potential of fistula-in-ano with abscess: analysis of 11 deaths.

ConclusionsThis report of seven deaths from fistula-in-ano with acute abscess in a seven-year period between 1962 and 1969 at the Philadelphia General Hospital indicates the serious potential of this generally-benign surgical lesion. Fistula-in-ano with acute abscess occurring in the obese or diabetic patient in association with local and systemic signs of invasive infection requires serious, considered management. Similarly, four deaths from the chronic form of fistula-in-ano during the same period indicate the debilitating nature of neglected fistula-in-ano, which can lead ultimately to death.

Guidelines for use of the flexible fiberoptic sigmoidoscope in the management of the surgical patient

Based on data from many clinical studies and programs, guidelines are presented for application of the flexible fiberoptic sigmoidoscope in the management of the surgical patient. The flexible fiberoptic sigmoidoscope has proved to be an instrument of extraordinary capability in detecting colorectal neoplasms with yields being two or three times greater than those of the rigid sigmoidoscope in the symptom-resolution, polyp and cancer surveillance patient categories. In addition, the practical advantages of the narrow diameter, flexibility, and length of the fiberoptic sigmoidoscope are readily appreciated when the surgeon finds that he can satisfactorily examine patients with rectal or sigmoid strictures, marked angulations, or contracted lumens in whom a rigid scope would be unsuitable. Data from the authors comparative study of more than 3000 patients have permitted the development of not only guidelines for the application of the flexible fiberoptic sigmoidoscope but an appreciation of the modified role of the rigid sigmoidoscope and the proper relationship between the flexible fiberoptic sigmoidoscope and the flexible fiberoptic colonoscope. A most important consideration is based on data regarding the site distribution of 400 benign premalignant neoplasms detected in the comparative study. The even distribution of these lesions throughout the terminal 50 cm of colorectum underscores the need to examine as much of the colorectum as possible.