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Biomedical subjects

A M Cohen

Publications and source records attributed to A M Cohen.

At least 91 records · Page 5Linked to original sources

Sphincter preservation in rectal cancer. Technical considerations for coloanal anastomosis and J-pouch.

Most patients with midrectal cancer undergo a sphincter-preserving operation using modern bowel stapling techniques. In patients with bulky tumors or unfavorable pelvic anatomy, however, abdominoperineal resection with permanent colostomy may be performed for technical reasons, not based on oncologic clearance needs. In addition, low-lying tumors treated initially with preoperative chemoradiation are often downstaged, increasing the opportunity for restorative procedures. Treatment by total proctectomy and peranal sutured coloanal reconstruction fulfills the need for adequate oncologic clearance and satisfactory bowel function. Sharp pelvic dissection with removal of the entire rectal mesentery, adequate mobilization of the left colon, and precise anastomotic technique are required for optimal results. Creation of a colon J-pouch increases the capacity of the reconstructed rectum and greatly reduces the time required for functional adaptation in the postoperative period. Although irregular evacuation and other minor problems can persist, permanent colostomy is avoided, and patient satisfaction is high. For cancers of the middle and distal rectum, total proctectomy with coloanal reconstruction is an important treatment option that can improve quality of life without compromising cancer treatment.

Abdomen↗

Stage I rectal cancer: identification of high-risk patients.

BACKGROUND: Stage I rectal cancer (T1, T2 N0) is currently treated by surgical resection alone. Despite adequate surgical resection, approximately 10-15% of patients will develop recurrence. Identification of patients at high risk for recurrence could potentially lead to an improvement in outcome by selection of these patients for adjuvant therapy. METHODS: Between June 1986 and September 1996, 211 patients with primary rectal cancer (stage I) were treated by radical surgical resection alone. The medical data of all patients were entered into a database and prospectively followed. The following 10 prognostic factors were correlated with recurrence and tumor-related mortality: patient factors: age, gender, and preoperative carcinoembryonic antigen level; tumor factors: location from the anal verge (< 6 cm vs. > or = 6 cm), T stage (T1 vs. T2), intratumoral blood vessel invasion (BVI), intratumoral lymphatic vessel invasion, presence of tumor ulceration, and histologic differentiation; and treatment-related factors: extent of surgical resection--abdominal perineal resection versus low anterior resection. Univariate analysis of the effect of the prognostic factors on recurrence and tumor-related mortality were performed by the method of Kaplan-Meier and log rank test. Independent prognostic factors were determined by a multivariate analysis performed using the Cox proportional hazards model. RESULTS: The overall 5-year actuarial recurrence was 12% and tumor-related mortality was 10%. Independent predictors of recurrence were male gender and BVI. Independent predictors of tumor-related mortality were male gender, BVI, and poorly differentiated tumors. CONCLUSIONS: Despite radical resection, patients with stage I rectal cancer with male gender, BVI, and poorly differentiated tumors should be considered high-risk patients.

Abdomen↗

Spectral morphometric characterization of B-CLL cells versus normal small lymphocytes.

Spectral morphometric characterization of typical chronic lymphocytic leukemia (B-CLL) cells vs normal small lymphocytes stained by May-Grunwald-Giemsa was carried out by multipixel spectral imaging. The light intensity (450-850 nm of 10(4) pixels) from nuclear domains of each stained cell was recorded and represented as light transmittance spectra and optical density. Transmitted light spectra of two nuclear domains were determined, one with low-intensity light transmittance (LIT) and the other with high-intensity light transmittance (HIT). A spectral library was constructed using the four transmitted light spectra representing the HIT and LIT domains of the normal human lymphocytes and the LIT and HIT domains of the CLL cells. The spectral library served to scan CLL lymphocytes from 10 cases of CLL and the lymphocytes of 10 healthy individuals. Each spectrally similar domain in the nuclei of the lymphocytes was assigned an arbitrary color. The morphometric analysis of the spectrally classified nuclei showed specific spectral patterns for B-CLL in 92% of the cells. The specific spectral characteristics of each of the two cell populations were also observed by their optical density light absorbance spectra. We propose that spectral morphometric analysis may serve as an additional diagnostic tool for detection of CLL lymphocytes in a hematological specimen.

Cell Nucleus↗

Granisetron and ondansetron for chemotherapy-related nausea and vomiting.

The efficacy of granisetron and ondansetron, two serotonin antagonists, as antiemetic agents was studied and compared in the first 24 h follow, by chemotherapy administration. Sixty cancer patients took part in this randomized prospective study. The patients were categorized according to the chemotherapy which was administered. Patients in group A received combinations including the highly emetogenic agents, cisplatinum or adriamycin, patients in group B received regimens which included neither of these agents. Both serotonin antagonists were highly effective, only 9 (16%) out of 58 patients suffered from vomiting, 7 (25%) of the patients on ondansetron and 2 (7%) on granisetron. Splitting the patients into both groups supported the above results. In group A (adriamycin-cisplatinum) only 7 patients (22%) reported vomiting, 5 (33%) on ondansetron vs 2 (12%) on granisetron. In group B, only 2 patients (8%) suffered from vomiting, both patients (15%) on ondansetron while no vomiting was seen in the granisetron patients. Similar results were obtained in preventing nausea in these patients. We conclude that both serotonin antagonists are effective in preventing nausea and vomiting in patients receiving chemotherapy. In all groups tested this study granisetron appeared to be superior, although, this difference failed to reach statistical significance due to the small number of patients analyzed. However, there was no difference in cost effectiveness between the regimens.

Antiemetics↗

Spectrally resolved imaging of Cabot rings and Howell-Jolly bodies.

The spectral characteristics of erythropoietic cellular inclusions stained by May-Grunwald Giemsa (MGG) were determined by spectrally resolved imaging. Multipixel spectra were obtained from Cabot rings and Howell-Jolly (HJ) bodies, displaying a range of wavelengths of transmitted light. The spectral characteristics of these inclusions were compared with those of isolated DNA, histones (type II) and arginine-rich histones (type VI), all stained by MGG. Results of single-cell spectroscopy show that the spectra of Cabot rings and HJ bodies share spectral characteristics with the type II and type VI histones. However, no resemblance was found between Cabot rings and DNA spectra. The spectral analysis of heterochromatin displayed a spectral pattern with characteristics of both DNA and histones, while the euchromatin showed a major contribution of the DNA component.

Chromatin↗

Single chain antigen binding protein (sFv CC49): first human studies in colorectal carcinoma metastatic to liver.

BACKGROUND: An sFv fragment of the anti-TAG-72 monoclonal antibody CC49 has been developed and has shown promise in improved targeting to colorectal carcinoma in animal studies. In this study the authors report their initial experience in human patients after intravenous injection. METHODS: Five patients with colorectal carcinoma metastatic to the liver were studied prior to surgery. High performance liquid chromatography showed a low level of aggregation (< 10% complex formation), before and after radiolabeling with iodogen. Prior to radiolabeling, 123I was brought to the dry form, phosphate buffer added and titrated to a pH of 7, with diluted hydrochloric acid. 123I was injected in doses of 26, 12, 27, 25 and 1 millicurie, respectively, and labeled to a 5-mg fragment. Single photon emission computed tomography and whole body imaging were performed at 4-6 hours, and 24 hours, respectively, after injection. RESULTS: The agent was rapidly cleared from the blood with biphasic clearance T-1/2 of 30 minutes and 10.5 hours, respectively. Distribution from whole body imaging confirmed rapid equilibration with extracellular fluid, and clearance T-1/2 from the body was comparable to the slower component of blood clearance. The spleen was visualized in all patients, and the testes were imaged in 67% of male patients. Renal excretion was noted with early uptake and clearance from the renal parenchyma except in one patient in whom renal parenchyma retention was intense. Although image quality was suboptimal, tumor was visualized in all five patients in both primary and metastatic lesions. At surgery, (16-24 hours postinjection), the tumor retained significant concentrations of the radiotracer, with metastatic tumor/normal liver ratios of approximately 1:5-3:1. No patient had any associated symptom or change in biochemical and hematopoietic status. CONCLUSIONS: This study showed that sFv is safe, tissue equilibration and clearance is rapid, and early, same-day imaging of the primary and metastatic tumors is feasible in patients colorectal carcinoma. Further studies are warranted to define a more optimal mass of sFv CC49 dose for tumor targeting.

Adult↗

Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil).

Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An earlier Phase I trial of 131I-labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5-FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days 1 and 5. In assessing the reduction in tumor volumes over the first 28 days of the experiment, 5-FU treatment (with or without leucovorin) in combination with 131I-mAb A33 showed a statistically significant additive antitumor effect compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were disease free at 276 days compared to none from any other group, suggesting a synergistic effect. These data indicate that Phase II clinical trials combining radiolabeled antibody therapy with 5-FU-based treatments are warranted.

Animals↗

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer.

PURPOSE: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. METHODS AND MATERIALS: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. RESULTS: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). CONCLUSION: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.

Adult↗

Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer.

PURPOSE: We report the downstaging, sphincter preservation, acute toxicity, and preliminary local control and survival results of preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and concurrent radiation therapy followed by postoperative LV/5-FU for treatment of patients with clinically resectable T3 rectal cancer. MATERIALS AND METHODS: A total of 32 patients received two monthly cycles of preoperative LV/5-FU (bolus daily X 5). Radiation therapy (5,040 cGy) began concurrently on day 1. Postoperatively, patients received a median of two monthly cycles of LV/5-FU (range, 0-10). RESULTS: The complete response rate was 9 percent pathologic and 13 percent clinical, for a total of 22 percent. Total Grade 3+ acute toxicity during the preoperative combined modality segment was 25 percent (8/32). Of the 20 patients who were thought to initially require an abdominoperineal resection and for whom the intent of treatment was sphincter preservation, 17 (85 percent) were able to undergo sphincter-preserving surgery. With a median follow-up of 22 (3-59) months, none have developed local failure, and the three-year actuarial disease-free survival rate was 60 percent. CONCLUSION: Our data reveal encouraging downstaging, sphincter preservation and acute toxicity with this regimen. Additional follow-up is needed to assess the long-term local control and survival rates.

Adenocarcinoma↗

Pancreaticoduodenectomy for nonperiampullary primary tumors.

INTRODUCTION: This review was performed to evaluate the outcome of patients undergoing pancreaticoduodenectomy (PD) for isolated metastatic or locally advanced nonperiampullary tumors at a single institution over a 13-year period. METHODS: Between 1983 and 1996, patients undergoing PD for metastatic or locally advanced nonperiampullary malignancies were identified. Medical records were reviewed and outcome factors and survival data analyzed. RESULTS: Eighteen patients were identified. The primary tumor histopathology included colon (n = 7), gastric (n = 4), renal cell (n = 3), lung (n = 2), bladder (n = 1), and melanoma (n = 1). The median length of hospital stay was 15 days (6 to 48) with one perioperative death (5.5%). The median tumor size was 5.5 cm (0.8 to 11.5), and 7 patients had positive peripancreatic lymph nodes. The median survival was 40 months, with a 5-year survival of 35%. CONCLUSIONS: Pancreaticoduodenectomy for nonperiampullary malignancy is infrequently indicated. However, in the absence of widely metastatic disease, PD should be considered for locally advanced tumors or isolated metastatic malignancy.

Carcinoma, Renal Cell↗

Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients.

BACKGROUND: Although prospective trials have demonstrated that postoperative chemotherapy for node-positive colon cancer patients provides survival benefit, no improvement in survival has been documented for node-negative colon cancer patients. There are, however, a subset of node-negative patients that go on to die of their disease. We hypothesize that this subset of node-negative patients may benefit from postoperative chemotherapy. We analyzed a large cohort of node-negative colon cancer patients from a single institution to determine prognostic factors that predict which patients with node-negative colon cancer might experience recurrence and can benefit from postoperative chemotherapy. STUDY DESIGN: A review of the prospective database for colorectal cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 1993 identified 572 patients who underwent curative resection for node-negative colon cancer (T(1,2,3,4)N0M0). Demographic, serum, and pathologic factors were analyzed for prognostic significance. Survival was calculated by the method of Kaplan-Meier and compared by log rank test. Multivariate analysis was calculated by the Cox proportional hazard model. RESULTS: Median follow-up was 35 months. Factors predictive of survival by univariate analysis include tumor stage, overall stage, and preoperative serum carcinoembryonic antigen (CEA) elevation. By multivariate analysis, overall stage and preoperative serum CEA level predicted survival. CONCLUSIONS: Routine histologic and demographic factors do not predict outcome in node-negative colon cancer patients. Preoperative CEA and overall stage predict survival by multivariate analysis. Preoperative CEA elevation in node-negative patients identifies a group of patients that has a poor prognosis and defines a subset of patients who may benefit from postoperative chemotherapy.

Adult↗

Ninety-six five-year survivors after liver resection for metastatic colorectal cancer.

BACKGROUND: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years. STUDY DESIGN: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed. RESULTS: Five-year survivors (n = 96) were more likely to have a Duke's B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%. CONCLUSIONS: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.

Adult↗

The influence of timing of ketorolac administration on post-operative analgesic requirements following total abdominal hysterectomy.

One hundred and thirty-seven patients were studied to assess whether the timing of a dose of ketorolac affected cumulative morphine requirements during the first 12 post-operative hours. Pain, sedation and nausea scores, respiratory rate and degree of operative blood loss were also recorded. Thirty-six patients (group A) were given placebo injections pre- and intra-operatively. Thirty-one patients (group B) received placebo pre-operatively and ketorolac 30 mg intra-operatively. Thirty-six patients (group C) received ketorolac 10 mg pre-operatively and ketorolac 20 mg intra-operatively and thirty-four patients (group D) were given ketorolac 30 mg pre-operatively and placebo intra-operatively. Post-operative analgesia was with intravenous (i.v.) morphine administered using a patient controlled analgesia (PCA) device. Analysis of variance revealed a significant difference in morphine consumption at 1, 2, 4, 8 and 12 h postoperatively (P < 0.05) between group A (no ketorolac) and groups B, C and D (ketorolac). However, there were no significant differences between groups B, C and D during the study period. Thus, the timing of ketorolac administration made no difference to overall morphine consumption. Pain, nausea, sedation and respiratory rate scores were similar in all four groups. There was a significantly greater blood loss in patients receiving ketorolac (groups B, C and D) compared with those receiving placebo alone (group A).

Adult↗