Blood vessel invasion in colorectal cancer--an alternative to TNM staging?
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Colorectal Neoplasms↗
Biomedical subjects
A M Cohen
Publications and source records attributed to A M Cohen.
Surgical salvage of recurrent rectal carcinoma after curative resection: a 10-year experience.
BACKGROUND: Local recurrence after resection of rectal carcinoma is a difficult clinical problem that adversely affects both survival and quality of life. Surgical resection is possible for a subset of patients with localized recurrences. We reviewed our experience with surgical salvage of recurrent rectal carcinoma, to determine predictors of resectability and postsalvage survival rates. METHODS: A 10-year, retrospective analysis of 131 patients who underwent exploration with curative intent for local recurrence after radical resection of rectal carcinomas, in a single referral institution, was performed. Preoperative and pathological factors were examined for their ability to predict postresection survival rates and resectability. RESULTS: The overall 5-year survival rate for patients who underwent exploration with curative intent was 24%. Resection of recurrent disease was possible for 103 of 131 (79%) patients, with a resulting 5-year survival rate of 31%. Patients who were treated initially with abdomino-perineal resection (n = 35) presented later and were less likely to have resectable tumors than were those treated initially with some form of sphincter-preserving resection (n = 96). Among patients who could undergo resection, normal carcinoembryonic antigen levels and recurrent disease limited to the bowel wall were both favorable features. CONCLUSIONS: Surgical salvage of local recurrence after radical resection of rectal carcinoma can be performed safely and can result in substantial long-term survival benefits for selected patients.
Combined Modality Therapy↗
Urinary diversion after total pelvic exenteration for rectal cancer.
BACKGROUND: Total cystectomy is indicated for the treatment of bulky primary rectal cancers as well as previously treated, locally recurrent tumors that invade the bladder, prostate, seminal vesicle, or urethra. We review a 10-year Memorial Sloan-Kettering Cancer Center experience with urinary diversion in this setting. METHODS: Between April 1988 and June 1998, 47 patients underwent urinary diversion during a total pelvic exenteration for rectal cancer. Charts and operative records were reviewed to determine pathological findings, short-term and long-term urological complications, and survival. RESULTS: Forty-seven patients (25 males and 22 females; median age, 62 years; age range, 27-79 years) were included. Sixteen (34%) patients underwent cystectomy for a primary rectal tumor (including 1 for rectal sarcoma and 1 for synchronous invasive bladder cancer), and 31 (66%) patients underwent surgery for a locally recurrent rectal cancer. Thirty (64%) patients underwent preoperative, 18 (38%) underwent intraoperative, and 11 (23%) underwent postoperative radiotherapy. Twenty-six (55%) patients received preoperative and 16 (34%) underwent postoperative chemotherapy. Two patients had continent ileal cecal reservoirs, 1 a colonic conduit, and the remaining 45 had ileal conduits. The tumor invaded the bladder in 24 (51%) patients, the prostate in 5 (11%) patients, and the seminal vesicle in 5 (11%) patients. Complete resection was achieved in 42 (89%) patients. There were a total of eight complications in eight (17%) patients. There were three early complications, two of which were ileoureteral anastomotic leaks, one managed by reoperation, the second by percutaneous drainage, and one moderate hydronephrosis managed expectantly. There were five late complications; three patients had ureteral stricture/stenosis, leading to nephrectomy in one patient and percutaneous stenting in two patients. Two patients developed late hydronephrosis, so far managed expectantly. There was one perioperative death. After a median follow-up of 16.83 months, 20 patients were dead of the disease, 6 were alive with disease recurrence, 2 were dead of other causes, and 19 had no evidence of disease. Three-year actuarial disease-specific survival was 34%. CONCLUSIONS: Complete resection of bulky primary or locally recurrent rectal cancer can be performed with acceptable urological morbidity. Complete resection was obtained in 89% of patients, with 72% having urological organ invasion. Overall urological complications of 17% are acceptably low despite intensive perioperative radiation and chemotherapy. Disease-specific survival in these patients remains limited.
Adult↗
Improved method for transjugular liver biopsy.
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Biopsy, Needle↗
Liver resection for metastatic colorectal cancer: assessing the risk of occult irresectable disease.
BACKGROUND: Liver resection is standard therapy for selected patients with metastatic colorectal cancer. Extrahepatic metastases and inability to remove all hepatic disease usually preclude curative resection and are the most common contraindications. This study analyzes irresectability in patients considered to have resectable disease taken to operation for potentially curative hepatic resection. We describe preoperative factors associated with irresectability and propose a preoperative scoring system that identifies patients at particularly high risk for occult irresectable disease. STUDY DESIGN: Patients considered to have resectable hepatic colorectal metastases were identified from a prospective database. Intraoperative findings that precluded liver resection were recorded. Demographic data, characteristics of the primary tumor, and characteristics of the hepatic metastases were recorded and analyzed. RESULTS: From April 1992 through July 1997, 416 patients were explored with the intention of performing a potentially curative liver resection; 329 (79%) were resected. Eighty-seven patients (21%) had apparently resectable tumors on preoperative imaging but irresectable disease at laparotomy. Forty-four patients (51%) had irresectable disease limited to the liver; 32 had extensive bilobar disease not appreciated before surgery, and 12 were not resected for technical or other reasons unrelated to disease extent. Forty-three patients (49%) had extrahepatic disease, 31 of whom had resectable hepatic tumors. Of the several preoperative factors analyzed, only the estimated number of hepatic tumors was an independent predictor of irresectable findings at operation. This held true for patients with extrahepatic metastases and those with extensive hepatic disease. From these data, we devised a preoperative scoring system that estimates the probability of finding occult irresectable disease. Resectability ranged from 95% in patients with a score of 0 (solitary, unilobar) to 62% in those with a score of 3 (multiple, bilobar; p = 0.0001). The predictive value of this scoring system was then validated by applying it prospectively to an additional group of 118 patients taken to surgery for resection; the results were similar. CONCLUSIONS: Standard preoperative investigations predicted resectability in 79% of patients with hepatic colorectal metastases. Unresectable disease limited to the liver and extrahepatic disease were seen with nearly equal frequency. The majority of patients with extrahepatic metastases had resectable hepatic disease (31 of 43, 72%). A preoperative scoring system is proposed that identifies patients at high risk for unrecognized irresectable disease and may help focus the use of additional diagnostic modalities such as laparoscopy and positron emission tomography (PET).
Colorectal Neoplasms↗
Biochemistry of the infarcted heart.
I am honored by the invitation to contribute to a volume in Neuroscience, dedicated to Professor Galoyan, whose accomplishments in the field of neuroscience and circulation have been unique. In his book, Dr. Galoyan has summarized the results of his discovery of cardioactive neurohormones. His discovery of biosynthesis of cytokines in the neurosecretory cells of the hypothalamus have opened a new page in immunology.
Animals↗
Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis.
Breakdown of basement membrane (BM) is believed to be an essential step for tumor invasion and metastases. We have previously demonstrated that matrix metalloproteinase-9 (MMP-9), the 92 kDa collagenase expression correlates with metastases in human colorectal cancer (CRC). This study explores the relationship between the 72 and 92 kDa type IV collagenase (MMP-2 and MMP-9) activities and pattern of type IV collagen expression during human colorectal tumorigenesis. Thirty-four CRC patients, including four synchronous adenomas and one synchronous liver metastases, were involved in this study. By immunohistochemical staining, type IV collagen expression was noted to be continuous in the BM of normal mucosa, adenoma and in two cases of carcinoma in situ. Limited or absent type IV collagen staining pattern was seen in 100 (19/19) and 23% (3/13) of CRC with and without metastases, respectively. By double immunostaining, MMP-9 protein expression was noted to localize within areas of limited type IV collagen staining. Similarly, type IV collagen staining was noted to be greatest in areas devoid of MMP-9 expression. Gelatin zymography detected both 92 and 72 kDa proenzyme forms in all CRC and normal mucosa extracts examined. The mean tumor/normal fold increases of the proMMP-2 and proMMP-9 enzyme forms were 1.6+/-0.1 (mean +/- SE) and 2.4+/-0.5 in adenomas, and 2.1+/-0.2 and 4.1+/-0.7 in CRC, respectively. The 62 and 82 kDa bands were present in 63 (12/19) and 74% (14/19) of CRC with metastases, compared with only 20 (3/15) and 33% (5/15) of CRC without metastases, respectively. These differences were significant (P = 0.045 and P = 0.030, respectively). Our results demonstrate that loss of BM type IV collagen along with elevations in MMP-2 and MMP-9 expression, especially the activated forms, occur during colorectal tumorigenesis. Our data suggest that control of type IV collagenase activation may be beneficial in preventing human colorectal tumor progression.
Adenoma↗
Safety and efficacy of low anterior resection for rectal cancer: 681 consecutive cases from a specialty service.
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%.
Adult↗
The effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling.
BACKGROUND: Patients with angina after a Q-wave myocardial infarction benefit from elective revascularization, but it is not known whether asymptomatic patients, including those with a totally occluded infarct-related artery, improve after revascularization. OBJECTIVE: To determine the effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling. METHODS: We prospectively studied 31 consecutive asymptomatic patients (aged 57 +/- 2 years, 24 with anterior infarcts) after Q-wave myocardial infarction with > or = 70% stenosis of the infarct-related artery (IRA) who underwent early elective revascularization (days 4-10 after myocardial infarction). Group I consisted in patients with a totally occluded IRA (n = 10), and group II consisted in patients with a patent, though stenosed, IRA (n = 21). Resting echocardiography and low-dose dobutamine echocardiography were performed at baseline (day 3 +/- 1), and rest echocardiography was repeated after an 8-week follow-up. Significant myocardial viability was defined as > or = 2 wall segments improved (in a 16-segment model of left ventricle) versus baseline, and significant functional recovery as > or = 2 segments improved versus baseline on follow-up examination. Left ventricular end-systolic volume indices (ESVI) and end-diastolic volume indices and ejection fractions were measured by using a modified version of Simpson's rule (using apical two-chamber and four-chamber views). RESULTS: The left ventricular ESVI of patients in group I had decreased by 4.2 +/- 1.9 ml/m2, whereas for patients in group II the left ventricular ESVI had increased by 4.2 +/- 1.7 ml/m2 (P = 0.006). Similarly, the left ventricular end-diastolic volume index had decreased by 0.7 +/- 2.4 ml/m2 versus baseline at follow-up for patients in group I and increased by 7.8 +/- 2.1 ml/m2 for patients in group II (P = 0.02). The left ventricular ejection fraction increased by 7.3 +/- 3% for patients in group I and decreased by 0.4 +/- 2% for patients in group II (P = 0.04). CONCLUSION: There is less global left ventricular remodeling, a potentially deleterious process, after elective revascularization early after Q-wave myocardial infarction in asymptomatic patients who had had a totally occluded IRA before revascularization than there is in patients who had already had a patent, though stenosed, IRA before revascularization. These results suggest that restoration of patency of IRA after a Q-wave myocardial infarction is beneficial even for asymptomatic patients.
Coronary Disease↗
Kaposi's sarcoma associated with Castleman's disease.
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Aged↗
Current issues in colorectal cancer surgery.
Increased understanding of the pathology and natural history of colorectal cancer has led to significant advances in the management of this disease. Surgical management of rectal cancer currently includes a spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques. At one end of the spectrum, 5% to 10% of patients present with small, superficially invasive rectal cancers amenable to a curative local excision. At the other end, a subset of patients present with locally advanced rectal cancers that require multimodality therapy, including sharp pelvic dissection with en-bloc resection of involved organs. However, the majority of rectal cancer patients present with nonfixed, yet deeply invasive, lesions requiring either a low anterior resection (LAR) or an abdominal perineal resection (APR). This report will address the controversies in the surgical management of colorectal cancer.
Anastomosis, Surgical↗
The role of surgery and chemoradiation therapy for cancer of the rectum.
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Adenocarcinoma↗
Effect of acetylsalicylic acid on nitric oxide production in infarcted heart in situ.
The effect of Acetylsalicylic Acid (ASA, Aspirin) on the myocardial production of the inducible form of nitric oxide synthase (iNOS) and the oxidation products of nitric oxide (nitrite, NO-2 and nitrate, NO-3: NOx) were studied in the rabbit heart two days after ligation of a branch of the left circumflex coronary artery. ASA was administered intravenously as AspisolR, DL-Lysinmono(acetylsalicylate) which is soluble in water. Animals received a total dose of 250, 375, or 500 mg/kg of ASA in five divided doses intravenously. Significant inhibition of iNOS was noted in the infarcted portion of the myocardium at 375 and 500 mg/kg of ASA. The reduction in myocardial nitric oxide (NO) production was paralleled by a diminution in coronary arterial-venous difference of NOx, demonstrating that ASA inhibition extended also to the oxidation products of NO. ASA is an inhibitor of cyclooxygenase (COX). The inhibition of iNOS by ASA demonstrates the close relationship between COX and iNOS activity in the heart in situ. Whether activity of the infarcted heart is influenced by the diminution in the production of NO by ASA is not known.
Animals↗
High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer.
PURPOSE: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). RESULTS: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery. CONCLUSION: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.
Adenocarcinoma↗
Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up.
BACKGROUND: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. METHODS: Thirty six patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (5,T2; 31,T3) involving the distal half of the rectum and clinically required an abdominoperineal resection. The median tumor size was 3.8 cm [range: 1.5-7 cm] and the median distance from the anal verge was 4 cm [range: 3-7 cm]. The whole pelvis received 46.80 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 56 months [range: 4-121 months]. RESULTS: Of the 35 patients who underwent resection, 5 (14%) had a complete pathologic response and 27 (77%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 5-year actuarial: 21%. The 5-year actuarial survival was 64%. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in the 27 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 85%. The median number of bowel movements/day was 2 (range: 0-8). CONCLUSIONS: Our data suggest that preoperative radiation therapy allows sphincter preservation in 77% of selected patients who would otherwise require an abdominoperineal resection, and 85% have good to excellent sphincter function. Given the moderate local failure rate, we now routinely use preoperative combined modality therapy plus postoperative chemotherapy for patients with clinical T3 disease.
Adenocarcinoma↗
In vitro detection of occult bone marrow metastases in patients with colorectal cancer hepatic metastases.
PURPOSE: The purpose of this study was to assess the immunocytochemical status of bone marrow aspirates from patients with clinically isolated hepatic metastases to test the hypothesis that such findings would allow improved patient selection for liver-directed treatment. METHODS: All patients had biopsy-proven or presumed colorectal cancer metastatic to the liver and were scheduled for an operative procedure for hepatic resection or for hepatic artery catheter and chemotherapy pump implant. Immunocytochemical analysis of bone marrow aspirate smears was performed with a panel of monoclonal antibodies directed toward cytokeratins, Lewis Y antigen and A-33 colorectal epitopes. RESULTS: Data from 80 patients indicated that bone marrow reactivity was present in 9.5 percent of those with resectable hepatic metastases and in 34 percent of those not resected (P = 0.03). No single monoclonal antibody or combination produced better discrimination. CONCLUSIONS: Presence or absence of presumed occult colorectal cancer cells in the bone marrow of patients with isolated hepatic metastases is biologically interesting, but not useful in selecting or altering patient management.
Antibodies, Monoclonal↗
Interventional uroradiology.
The development of interventional uroradiologic techniques has had a major impact on the care of the urologic patient by allowing nonoperative treatment of many disease processes. This article will review percutaneous nephrostomy with emphasis on urologic calculi, interventional therapy for neoplasms and trauma of the urinary tract, diagnosis and treatment of renovascular hypertension, and the management of complications following renal transplantation.
Humans↗
Intracerebroventricular administration of leptin markedly enhances insulin sensitivity and systemic glucose utilization in conscious rats.
This study examines the acute, subacute (overnight), and chronic (7-day) effects of intracerebroventricular (i.c.v.) administration of r-metMuLeptin on insulin sensitivity and systemic glucose turnover in conscious unrestrained rats (body weight, 250 to 300 g). Under postabsorptive conditions, acute i.c.v. leptin ([AL] 10 microg bolus) did not affect tracer (3-(3)H-glucose)-determined glucose production (GP) and utilization (GU) rates during the 2-hour hyperinsulinemic (2 mU x kg(-1) x min(-1)) euglycemic clamp. Chronic i.c.v. leptin ([CL] 10 microg/d for 7 days) administered by osmotic pumps markedly reduced the daily food consumption (P < .05), body weight (P < .05), and postabsorptive basal plasma glucose level (P < .01). During the glucose clamp, GP was markedly suppressed (55%) with CL (P < .001 v vehicle and pair-fed control groups). The insulin-induced increment in GU was significantly greater with CL (23.3 +/- 1.8 mg(-1) x kg(-1) x min(-1)) than with vehicle (16.9 +/- 0.2) and pair-feeding (17.1 +/- 0.6, both P < .001). Subacute i.c.v. leptin ([SL] 10 microg bolus) moderately but insignificantly decreased overnight food consumption (-18%) and body weight (-2.5 +/- 1.5 g). The glucose infusion rate during the final 60 minutes of the glucose clamp was 43% greater than for the vehicle group (P < .0001). SL also significantly increased GU (P < .005) and suppressed GP (P < .05) during the glucose clamp. Thus, we conclude that i.c.v. administered leptin has strong actions on the central nervous system that result in significant increases in insulin sensitivity and systemic GU, and these effects are achieved as early as overnight after leptin administration.
Animals↗