Selective loss of estrogen receptor beta in malignant human colon.

Epidemiological data suggest a protective effect for estrogen replacement therapy on colon cancer. The estrogen receptor (ER) is required for the action of estrogen. The ER-beta isoform is functionally similar to ER-alpha but has a distinct pattern of expression and transcriptional response to selective estrogen response modulators. Our goal was to investigate the presence of ER-alpha and ER-beta in normal and malignant colon tissue. Human colon cancer tissue and adjacent normal colon tissue were harvested from five male and six female patients undergoing segmental colon resection for colon cancer. Western blot analysis revealed very low levels of ER-alpha protein in tumor and normal colon tissue. In both male and female patients, malignant colon tissue showed a selective loss of ER-beta protein expression when compared to normal colon tissue in the same patient. Semiquantitative reverse transcription-PCR revealed no difference in ER-beta mRNA levels between normal and malignant colon tissue. Malignant transformation of the colon is associated with a marked diminution of ER-beta protein expression, possibly through a posttranscriptional mechanism.

Albumin supplementation in the critically ill. A prospective, randomized trial.

Albumin replacement to correct hypoalbuminemia in critically ill patients has been controversial. This study was a prospective, randomized trial of 25% albumin administration in 40 hypoalbuminemic (serum albumin, less than 25 g/L [2.5 g/dL]), critically ill patients. The treatment group (18 patients) received 25% albumin supplementation to achieve and maintain serum albumin levels of 25 g/L (2.5 g/dL) or greater, while the nontreatment group (22 patients) received no concentrated albumin. There was no clinical benefit from albumin therapy when assessing mortality (39% vs 27%, treatment vs control) or major complication rate (89% vs 77% of patients). There were also no significant differences in length of hospital stay, intensive care unit stay, ventilator dependence, or tolerance of enteral feeding, despite significant elevations of albumin in the treatment group. The costly use of exogenous albumin as treatment for hypoalbuminemia in this patient population does not appear to be justified.

The accuracy of laparoscopic ultrasound in the detection of colorectal cancer liver metastases.

BACKGROUND: The most sensitive and specific method of detecting colorectal cancer hepatic metastases has been shown to be a combination of careful intraoperative palpation and intraoperative ultrasound. Although there has been growing interest in laparoscopic surgical therapy for colorectal cancer, the ability of this technique to adequately evaluate the liver for small metastases has been unknown. This study was undertaken to compare laparoscopic liver ultrasound to the gold standard of open palpation and intraoperative ultrasound in detecting hepatic metastases from colorectal cancer. METHODS: A preliminary animal model was first performed in adult pigs. Eighteen liver "lesions" were created with chlorhexidine gluconate under laparoscopic guidance. A blinded surgeon then performed laparoscopic liver ultrasound followed by open ultrasound and palpation, comparing the accuracy of these techniques in detecting the lesions. In a second study, 15 patients undergoing laparotomy for colorectal cancer underwent preliminary laparoscopic liver ultrasound followed by open palpation and intraoperative ultrasound to compare these methods of liver evaluation. RESULTS: Laparoscopic liver ultrasound detected 17 of 18 lesions created in the pig livers, for a sensitivity of 94.4%. There were two false negatives, for a specificity of 77.7%. Laparoscopic liver ultrasound detected 4 of the 5 liver metastases in the human study, for a sensitivity of 80%. There was a single false negative, for a specificity of 90.9%. Several technical difficulties and their solutions are discussed. CONCLUSIONS: With several technical modifications guided by our initial experience, we believe laparoscopic liver ultrasound can be an effective way of evaluating the liver for metastases during laparoscopic colorectal resection for cancer.

Impact of gastric restrictive surgery on hypertension in the morbidly obese.

Hypertension is a major health risk factor in patients who are morbidly obese. Two hundred eighty-nine morbidly obese patients undergoing gastric restrictive surgery were evaluated for the presence of hypertension (blood pressure greater than or equal to 160/90 mm Hg or currently undergoing antihypertensive therapy) pre- and postoperatively. Of 74 (26%) preoperatively hypertensive patients, 67 (91%) were available for follow-up. Preoperative hypertension resolved in 66% (44 of 67) of patients following gastric restrictive surgery. Superobese and morbidly obese patients had similar reductions in hypertension after surgery (69% versus 63%). Patients not receiving antihypertensives preoperatively had a greater reduction of hypertension than those medically treated preoperatively (78% versus 58%). The amount of weight loss significantly predicted the reduction of hypertension, whereas follow-up weight achieved did not. The amounts of weight loss for patients with resolved and persistent hypertension were 89.3 +/- 5.6 lbs (mean +/- standard error of the mean +ADSEM+BD) and 66.0 +/- 8.3 lbs, respectively (p less than 0.02). For patients with resolved hypertension, follow-up weights for the morbidly obese and superobese were 162.0 +/- 10.8 lbs (133% +/- 4% ideal body weight +ADIBW+BD) and 220.4 +/- 9.5 lbs (170% +/- 7% IBW). Gastric restrictive surgery is effective therapy for hypertension in morbidly obese patients. Patients need not achieve weights approaching IBW to enjoy the benefits of gastric restrictive surgery on hypertension.

The frequency and clinical significance of neuroendocrine cells within stage III adenocarcinomas of the colon.

BACKGROUND: Although colon carcinomas consisting predominantly of neuroendocrine cells carry a worse prognosis than "routine" colon adenocarcinomas, the clinical significance of scattered neoplastic neuroendocrine cells within a typical colon adenocarcinoma remains controversial. The aim of this study was to document the frequency and clinical significance of neuroendocrine cell expression within a stage-specific group of typical adenocarcinomas of the colon. METHODS: Forty-eight patients with resected stage III adenocarcinomas of the colon were selected from our institutional tumor registry. The pathologic specimens from these patients were reviewed and underwent immunohistochemical staining for chromogranin, a sensitive and specific marker of neuroendocrine differentiation. Long-term (> or = 5 years) clinical outcome was compared with the presence of neuroendocrine cell expression. RESULTS: Twenty tumors (41.7%) stained positively for chromogranin. Twenty-two patients (45.8%) had long-term cancer-free survival, although chromogranin positivity did not correlate with this survival. CONCLUSION: The frequency of scattered neuroendocrine cells within colonic adenocarcinomas is high. This finding does not, however, carry the same adverse prognostic implications for cancer survival as does the presence of true neuroendocrine carcinoma of the colon.

Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expression.

PURPOSE: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation. METHODS AND MATERIALS: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later. RESULTS: Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively). CONCLUSIONS: The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.

Genetic syndromes and genetic tests in colorectal cancer.

Our understanding of the biology of colon cancer has matured to the point that it is a useful general paradigm for understanding solid tumor development. Recent advances provide insight into the genetic alterations underlying the development of colon cancer. These insights provide unique opportunities for genetic testing in predisposed, asymptomatic patients that can direct screening efforts and their clinical management. This review examines several inherited colon cancer predispositions, well described clinically for a century, that are now amenable to genetic testing. Additional discussion focuses on colon cancer predisposition traits that occur with high frequency but low penetrance characteristics. Finally, genetic tests for tumor markers that potentially have prognostic or therapeutic implications are reviewed.

Rediversion after ileal pouch-anal anastomosis. Causes of failures and predictors of subsequent pouch salvage.

PURPOSE: The aim of this study was to understand better the cause and predictability of pouch failure requiring rediversion after ileal pouch-anal anastomosis and to assess the ultimate outcome of patients in a large ileal pouch series who required rediversion. METHODS: Data from 460 patients completing ileal pouch-anal anastomosis at one institution were recorded from both a prospectively accumulated ileal pouch registry and patient medical records. RESULTS: Of 460 patients, 21 (4.6 percent) who underwent ileal pouch-anal anastomosis required rediversion. Five of these patients subsequently had successful restoration of pouch continuity, leaving a permanent failure rate of 16 of 460 patients (3.5 percent). The most common reasons for rediversion were pouch fistula formation (12) and poor functional results (5). Preoperative factors, including age, previous colectomy, and indication for colectomy, did not predict eventual need for rediversion. Patients requiring rediversion had significantly higher rates of postoperative complications (95 vs. 43 percent; P < 0.001). Specifically, this group had a higher rate of postoperative pouch fistula (57 vs. 3.4 percent; P < 0.001). Additionally, a final diagnosis of Crohn's disease significantly predicted the need for rediversion. Permanent pouch failure occurred in 36.8 percent of patients with a final diagnosis of Crohn's disease compared with 1.4 percent of patients with a final diagnosis of ulcerative colitis (P < 0.001). All five salvaged patients had fistula formation in the absence of Crohn's disease. CONCLUSIONS: The overall rate of permanent pouch failure is low. The majority of failures were related to fistula formation associated with Crohn's disease or poor functional results. Pouches complicated by fistulas not associated with Crohn's disease can be salvaged with temporary rediversion.