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Publications and source records attributed to B Minsky.
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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 high-grade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.
For intra-pelvic recurrence of rectal cancer, surgical resection is technically difficult and must be aggressive to achieve a high rate of negative resection margins. Resection with clear margins can be curative, particularly for those patients with true anastomotic recurrence. HDR-IORT is a safe, feasible, versatile, logistically sound modality that is highly reliable in delivering radiation to at-risk surgical margins in the pelvis. Despite surgery and IORT, overall local failure rates in this population are 33 to 50 percent. The most important prognostic variable is the state of surgical resection margins. At our institution, in patients with negative and positive resection margins the 2-year actuarial local recurrence rates are 33 percent versus 73 percent and 5-year survival rates are 51 percent versus 16 percent, respectively. On subset analysis, the most favorable outcome was seen in patients with true anastomotic recurrences (78 percent 5-year survival).
This article summarises the progress that has been made in the adjuvant treatment of colorectal cancer over the last decade. In view of the consequent improvements in recurrence rates and in overall survival, the development of effective adjuvant treatments for colorectal cancer is considered as one of the most important to be made in clinical oncology over the last decade. Treatment recommendations based on evidence-based data and on expert opinions are summarised in this manuscript. However, a consensus cannot be reached on all aspects of treatment because of data that is currently emerging that will influence clinical practice and because of the many ongoing clinical trials. Those involved in the treatment of colorectal cancer should therefore be encouraged to continue to provide optimal patient care and to participate in well designed clinical trials in order to increase the evidence upon which they can base their clinical judgements and in order to make further progress.
PURPOSE: Although sphincter-preservation procedures have replaced abdominoperineal resection as the treatment of choice for rectal cancer, a subset of patients with rectal cancer will still require abdominoperineal resection. The use of adjuvant radiotherapy has been shown to reduce local recurrence, and combined modality therapy (chemoradiation) improves survival. Sharp mesorectal excision compared with the classic teaching of blunt retrorectal dissection is also an important component of local control. The primary aim of the present study was to evaluate the postoperative complications associated with neoadjuvant therapy in patients requiring complete rectal excision. Oncologic outcomes for all patients with abdominoperineal resection are also provided. METHODS: A prospective database of 5,634 patients who underwent surgery for colorectal cancer at Memorial Sloan-Kettering Cancer Center between the years 1987 and 1997 was reviewed. Patients with primary adenocarcinoma of the rectum who underwent abdominoperineal resection were identified. In 1,622 patients who were operated on for primary rectal cancer, 292 patients (18 percent) underwent abdominoperineal resection and the rest had a sphincter-preserving procedure. Ten patients were excluded from the study because of prior pelvic irradiation for other cancer (8 patients) and insufficient radiation dose (<4,000 cGy; 2 patients). Neoadjuvant radiotherapy was given to 123 patients and postoperative adjuvant radiotherapy to 65 patients, whereas 94 did not receive radiotherapy. Intraoperative radiotherapy combined with preoperative radiotherapy was administered to 23 of the 123 patients given neoadjuvant radiotherapy. RESULTS: The duration of the operation was significantly longer in both neoadjuvant radiotherapy and intraoperative radiotherapy groups compared with the nonradiotherapy group (P = 0.01 and P < 0.0001, respectively). Estimated blood loss, mean number of blood units transfused per patient, and the percentage of patients being transfused were similar among the groups. Early postoperative complications were significantly higher in the neoadjuvant radiotherapy groups compared with the nonradiotherapy group. Late complications, overall survival, disease-free survival, and local recurrence were not significantly different among the groups. CONCLUSIONS: In patients with cancer of the lower one-third of the rectum, sharp pelvic dissection can result in a low rate of local recurrence even without radiotherapy. The role of preoperative radiotherapy, although associated with higher perineal wound complications, is important in increasing resectability and sphincter-preservation rate. Randomized, prospective trials will be needed to establish the role of adjuvant radiotherapy in patients undergoing sharp mesorectal excision for rectal cancer.
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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.
OBJECTIVE: To determine perioperative morbidity, survival, and local failure rates in a large group of consecutive patients with rectal cancer undergoing low anterior resection by multiple surgeons on a specialty service. The primary objective was to assess the surgical complications associated with preoperative radiation sequencing. SUMMARY BACKGROUND DATA: The goals in the treatment of rectal cancer are cure, local control, and preservation of sphincter, sexual, and bladder function. Surgical resection using sharp perimesorectal dissection is important for achieving these goals. The complications and mortality rate of this surgical strategy, particularly in the setting of preoperative chemoradiation, have not been well defined. METHODS: There were 1233 patients with primary rectal cancer treated at the authors' cancer center from 1987 to 1995. Of these, 681 underwent low anterior resection and/or coloanal anastomosis for primary rectal cancer. The surgical technique used the principles of sharp perimesorectal excision. Morbidity and mortality rates were compared between patients receiving preoperative chemoradiation (Preop RT, n = 150) and those not receiving preoperative chemoradiation (No Preop RT, n = 531). Recurrence and survival data were determined in patients undergoing curative resection (n = 583, 86%) among three groups of patients: those receiving Preop RT (n = 131), those receiving postoperative chemoradiation (Postop RT, n = 110), and those receiving no radiation therapy (No RT, n = 342). RESULTS: The perioperative mortality rate was 0.6% (4/681). Postoperative complications occurred in 22% (153/681). The operative time, estimated blood loss, and rate of pelvic abscess formation without associated leak were higher in the Preop RT group than the No Preop RT group. However, the overall complication rate, rate of wound infection, anastomotic leak, and length of hospital stay were no different between Preop RT and No Preop RT patients. With a median follow-up of 45.6 months, the overall actuarial 5-year recurrence rate for patients undergoing curative resection (n = 583) was 19%, with 4% having local recurrence only, 12% having distant recurrence, and 3% having both local and distant recurrence, for an overall local recurrence rate of 7%. The actuarial 5-year overall survival rate was 81%; the disease-free survival rate was 75% and the local recurrence rate was 10%. The overall survival rate was similar between Preop RT (85%), Postop RT (72%), and No RT (83%) patients (p = 0.10), whereas the disease-free survival rate was significantly worse for Postop RT (65%) patients compared with Preop RT (79%) and No RT (77%) patients (p = 0.04). CONCLUSION: The use of preoperative chemoradiation results in increased operative time, blood loss, and pelvic abscess formation but does not increase the rate of anastomotic leaks or the length of hospital stay after low anterior resection for rectal cancer. The 5-year actuarial overall survival rate for patients undergoing curative resection exceeded 80%, with a local recurrence rate of 10%.
PURPOSE: The purpose of this study was to assess the feasibility of 103Pd brachytherapy in the management of primary unresectable carcinoma of the pancreas. METHODS AND MATERIALS: Between August 1988 and January 1992, 11 patients with biopsy-proven primary unresectable adenocarcinoma of the pancreas were treated with 103Pd brachytherapy during laparotomy. The median age was 66 (range 57-70). The most common presenting symptoms were weight loss (eight patients), pain (six patients), and nausea/vomiting (four patients). Less common symptoms were jaundice (two patients), early satiety (two patients), and ascites (one patient). All patients underwent laparotomy and surgical staging. Eight patients had T3N0M0 disease, two patients had T3N1M0 disease, and one patient had T3N1M1 disease. The surgical procedure performed was biliary bypass in six patients, biopsy only in four patients, and gastric bypass in one patient. The average tumor dimension was 4.0 cm. The median activity, matched peripheral dose (MPD) and implanted volumes were 95.3 mCi, 124.4 Gy, and 33 cm3, respectively. The median initial dose rate was 0.21 Gy per hour. Five patients received postoperative external beam radiation therapy (median 45 Gy) and seven patients received chemotherapy postoperatively. The median follow-up was 7 months (range 1-19). RESULTS: The median survival for the entire group of patients was 6.9 months. Ten of 11 patients have died, with 1 patient presently alive and receiving chemotherapy for metastatic disease to the liver, but without local progression radiographically. Five of 11 patients (45%) were locally controlled, defined as either a complete response or freedom from progression at the site of the implant as evaluated by computed tomography scan. In the other six patients, the median time to local progression was 6.9 months. Five patients developed distant metastases (four liver, one subcutaneous nodule). Two patients failed in regional sites (one omentum, one paraaortic lymph node). Four of 11 patients (36%) developed acute postoperative complications that included one gastric outlet obstruction, one duodenal perforation, and two with sepsis. One of 11 patients (9%) developed a late complication of radiation enteritis 5 months after implantation. The median survival for patients experiencing complications was 1.7 months as compared to 8.4 months for the patients who did not develop a complication (p = 0.10). Pain relief was obtained in five out of six (83%) of the patients presenting with pain for a median duration of 24 weeks. Local control did not appear to be related to the MPD, dose rate, implanted volume, treatment with external beam irradiation, or the use of chemotherapy. Patients were more likely to develop a complication if the MPD was greater than 115 Gy (four out of six patients) as compared to those whose MPD was less than 115 Gy (one out of five patients) (p = 0.12). CONCLUSIONS: Because there was no improvement in median survival over conventional modalities, and the complication rate was high; we do not recommend 103Pd brachytherapy as a component of the treatment of unresectable adenocarcinoma of the pancreas.
BACKGROUND: A Phase I trial was performed to determine the maximum tolerated dose of concurrent preoperative radiation therapy (5040 cGy) and 2 cycles (bolus daily times 5) of 5-fluorouracil (5-FU) and low-dose leucovorin (LV) (20 mg/m2), followed by surgery and 10 cycles of postoperative 5-FU/LV in patients with primary or recurrent rectal cancer. METHODS: Twenty-four patients were entered into the study. Preoperatively, the initial dose of 5-FU was 325 mg/m2. 5-FU was escalated 50 mg/m2, while the dose of LV and radiation therapy remained constant. Chemotherapy and radiation began concurrently on day 1. The postoperative chemotherapy was not dose escalated; 5-FU, 425 mg/m2, and LV, 20 mg/m2. The median follow-up was 10 months (range, 4-19 months). RESULTS: The resectability rate with negative margins in the 23 patients who underwent surgery was 100%. One patient refused surgery. The pathologic complete response rate was 13% (3 of 23). An additional four patients had negative nodes and a microscopic foci of tumor in the bowel wall. Therefore, the total clinical complete response rate was 30% (7 of 23). The maximum tolerated dose of 5-FU for the preoperative combined modality segment was 375 mg/m2; therefore, the recommended Phase II dose level is 325 mg/m2. The incidence of Grade 3+ toxicity for the 22 patients treated at the recommended 5-FU dose level (325 mg/m2) during the preoperative combined modality segment was as follows: diarrhea, 14%; erythema, 5%; hematologic, 10%; and total, 18%. The median nadir counts were leukocyte count, 3.7 (range, 1.5-5.9); hemoglobin count, 12.2 (range, 10.2-14.3); and platelet count (times 1000), 165 (range, 92-237). CONCLUSIONS: With this regimen, the recommended doses of chemotherapy in the combined modality segment are slightly higher than those recommended in arm 2 of the Intergroup postoperative adjuvant rectal trial 0114. This regimen will serve both as the preoperative arm of the Intergroup randomized trial of preoperative versus postoperative combined modality therapy for resectable rectal cancer (INT R9401) as well as the basis for the combined modality segment of NSABP RO-3.
Tracheal metastases are rarely seen from colorectal carcinoma. We describe the third reported case of colorectal carcinoma metastatic to the trachea and review of the current pathogenesis, diagnosis, and management of endotracheal metastases.
This article focuses on the role of external beam radiation therapy, both in the primary and adjuvant setting. Much of the discussion is limited to the results of the randomized trials. In the setting where randomized trials are not available, selected nonrandomized series are discussed.
Intraluminal brachytherapy with a transcatheter Iridium-192 (Ir-192) wire, as a method to deliver a boost to patients with tumors of the extrahepatic bile ducts, has been well described. A major limitation of current imaging techniques is the inability to accurately define the proximal, distal, and most importantly the lateral extent of the tumor. We have found endoluminal ultrasound, which to this date has been used primarily to measure arterial wall layers, can successfully determine tumor volume in the bile ducts. The small diameter of these ultrasound probes allows easy insertion into a biliary duct drainage tube. Given the uncertainties in the determination of tumor size in the bile ducts, ultrasound is an ideal method by which to obtain the measurements. We present a case of recurrent islet cell carcinoma treated with external beam radiation therapy and an Ir-192 intraluminal brachytherapy boost in which the ultrasound probe was used to determine the tumor volume and response to therapy.
Transperineal 125iodine implants of the prostate can be performed with ultrasound guidance, a simple technique that has met with widespread acceptance. However, ultrasound does not allow good visualization of the pubic bones in relation to the pelvic outlet, and the pubic bones may interfere with needle placement in the anterior peripheral aspect of the prostate. Adequate irradiation of the entire periphery of the prostate is important to assure tumor control, since most tumors are multicentric and may involve the anterior aspect of the prostate. A computerized tomography-based treatment planning procedure that allows for angulation of transperineal needles to avoid the pubic bones and still reaches the most peripheral aspects of the gland is described. The technique also allows for the use of transrectal ultrasound and fluoroscopy to verify correct needle placement in the prostate at the procedure. Early treatment results, based on prostate specific antigen and regression of palpable tumors, are encouraging.
One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.
Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.
A number of investigators have examined the influence of vascular invasion by tumor in colon, rectal, and colorectal cancer. Some consider the presence of vascular invasion an unfavorable prognostic feature and propose treatment recommendations based on its presence. Vascular invasion has two distinct components: blood vessel invasion and lymphatic vessel invasion. The use of elastic tissue stains enhance both the detection of blood vessel invasion and its differentiation from lymphatic vessel invasion. Almost all series report an increased incidence of blood vessel invasion with increasing stage and grade. Although the influence of blood vessel invasion and lymphatic vessel invasion on patterns of failure is variable, both are associated with a decrease in survival; however, treatment recommendations based solely on the presence of blood vessel invasion or lymphatic vessel invasion should be made with caution.
The purpose of this study was to investigate the role of diagnostic laparoscopy in the multimodality management of locally advanced, near-obstructing rectal cancer. Fourteen patients with near-obstructing adenocarcinoma of the rectum (8 men and 6 women; mean age 49 years) underwent staging laparoscopy and formation of a sigmoid loop colostomy (n = 7), transverse colostomy (n = 4), or ileostomy (n = 3). The mean operative time was 78 minutes (range 67 to 94 minutes). All patients began a regular diet on postoperative day 1 and the median time to discharge was 4 days (range 2 to 8 days). Four patients were found to have diffuse peritoneal carcinomatosis not defined on preoperative CT scan. These patients died of disease within 6 months. Ten patients with advanced, localized pelvic disease began preoperative combined-modality treatment (5040 cGy external-beam radiation therapy in conjunction with 5-fluorouracil/leucovorin) between 8 and 13 days (median 9 days) following laparoscopy, and all underwent successful resection with clear margins in a median time of 12 weeks following laparoscopy. In the initial management of patients with near-obstructing advanced rectal cancer, laparoscopy can be both therapeutic and diagnostic by clarifying the site of the primary tumor, identifying patients with unsuspected peritoneal disease, and facilitating the formation of a defunctioning stoma with minimal morbidity. This leads to the early commencement of preoperative combined-modality treatment and does not compromise the prospects of subsequent tumor resection.