Multicenter nonrandomized trial of ramosetron versus palonosetron in controlling chemotherapy-induced nausea and vomiting for colorectal cancer

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) have a negative impact on patients' quality of life and frequently pointed to as a major factor for treatment abandonment. Serotonin (5-HT3) receptor antagonist is considered as key treatment for CINV. Ramosetron and palonosetron are recently developed 5-HT3 receptor antagonists and known as more superior than other first-generation 5-HT3 receptor antagonists. The purpose of this study was to compare the efficacy of ramosetron and palonosetron and determine which drug is more effective for prevention of CINV. METHODS: Colorectal cancer patients treated with chemotherapy were enrolled consecutively. Patients were assigned to receive intravenous injection of ramosetron 0.3 mg or palonosetron 0.25 mg at 30 minutes before initiation of moderately emetogenic chemotherapy. Ramosetron group added oral administration of 0.1 mg ramosetron on the second and third days of chemotherapy. Efficacy parameter consisted of nausea and vomiting. RESULTS: Ninety-one patients received ramosetron and 89 patients received palonosetron. Presentation of vomiting and nausea symptoms was not significantly different between the two groups during acute (0-24 hours) and delayed period (after 24 hours). CONCLUSION: The incidence of CINV between the ramosetron and the palonosetron group has not shown any difference during acute, delayed, and overall period.

ERRATUM: Correction for affiliation of the 8th author-corresponding author. Multicenter nonrandomized trial of ramosetron versus palonosetron in controlling chemotherapy-induced nausea and vomiting for colorectal cancer

The affiliation of the 8th author was misprinted.

Prospective multicenter phase II clinical trial of FOLFIRI chemotherapy as a neoadjuvant treatment for colorectal cancer with multiple liver metastases / 대한외과학회지

PURPOSE: This study evaluated the efficacy of neoadjuvant chemotherapy combining 5-flurouracil/folinic acid with irinotecan (FOLFIRI) in colorectal multiple liver metastases regardless of resectability. METHODS: Forty-four patients with multiple (at least two) colorectal liver metastases were enrolled at seven tertiary referral hospitals between May 2007 and September 2010. All patients received the FOLFIRI chemotherapeutic regimen. Response to chemotherapy was assessed after three cycles (6 weeks) and once more after six cycles (12 weeks) of treatment. RESULTS: Objective response was noted in 27 patients (61.4%) and 4 patients (9.1%) had progressive disease. Of 44 patients, 10 patients (22.7%) underwent curative surgery (R0 resection) and 34 patients did not receive R0 resection. Grades 3 to 4 hematological toxicity was noted in 12 patients (27.3%) and grades 3 to 4 nonhematologic toxicity was identified in 5 patients (11.4%). CONCLUSION: FOLFIRI chemotherapy as a neoadjuvant chemotherapy for multiple colorectal liver metastases regardless of resectability demonstrated the possibility of R0 resection, high rate of objective response, and tolerable toxicities in this study.

Expression of the survivin-2B splice variant related to the progression of colorectal carcinoma / 대한외과학회지

PURPOSE: Recently, two alternatively spliced survivin variants, survivin-DeltaEx3 and survivin-2B, were identified in a single copy of the survivin gene. It has been reported that the expressions of survivin splice variants significantly correlates with the clinical results in many types of human carcinoma. We investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and analyzed correlations between survivin expression levels and clinicopathologic features. METHODS: We used Western blot and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) to analyze the protein and mRNA expression levels of survivin variants in 51 colorectal carcinomas. The quantitative RT-PCR was performed using primer pairs specific for survivin and each of its splice variants, then normalized for the gene that encodes glyceraldehydes-3-phosphate dehydrogenase. RESULTS: In Western blotting, the protein levels of survivin were higher in the tumor tissue than in normal tissue. The expression of survivin, survivin-2B and survivin-DeltaEx3 mRNA was present in 96%, 64.7%, and 82.4% of the samples, respectively. When the pathologic parameters were compared, colorectal cancers of advanced pT stages showed significant decrease in survivin-2B mRNA expression by the quantitative RT-PCR (P < 0.001). CONCLUSION: The decreased expression of survivin-2B might be related to tumor progression in colorectal cancers. This finding indicates that alternatively spliced variants of survivin may be involved in refining the functions of survivin during tumor progression.

Topographic expression of p21WAF1/SDI1/CIP1, bcl2, and p53 is altered at the early stage of colorectal carcinogenesis

We analyzed the expression of p21, bcl2, and p53 in normal and different pathologic mucosa of the human colorectum using immunohistochemistry and cold polymerase chain reaction-single strand conformation polymorphism. The topography of normal mucosa showed; bcl2 and p53 expression restricted to basal epithelial cells and p21 expressed only in superficial epithelial cells. This topographic expression was altered in hyperplastic polyps and adenomas. Hyperplastic polyps revealed absence of or weak bcl2 expression and strong p21 expression without topography. In adenomas, whereas bcl2 expression increased and extended to parabasal and superficial dysplastic epithelium, the increase of p21 expression was limited to surface dysplastic epithelium. p53 was weakly expressed throughout the full thickness of dysplastic epithelium. Bcl2 expression in adenomas was stronger than in carcinomas; p53 expression was converse and p21 expression was variable. In carcinomas, this topographic expression was largely abrogated but p53 mutation (36%) was more frequent than in adenomas (2%). In carcinomas, p21 and p53 expression correlated inversely, but there was no relationship with bcl2. These results suggest that there is precisely ordered topographic pattern of p21, bcl2, and wild p53 expression in normal colorectal cells, but this becomes disordered during the early stage of colorectal carcinogenesis.

Counseling for Breast Disease Using the Internet

PURPOSE: Rapid progress in the development of communication devices has enabled us to use large amounts of various kinds of medical information, regardless of time or place. Today, in Korea there are many homepages on the web which provide medical information, hospital information, and counseling on medical fields in Korea, but more detailed recent medical informations, better quality control, and a greater variety of communication skills are needed. Methods and RESULTS: We analysed the data on the web from November 1998 to October 1999 about breast cancer clinic. The frequent questions were about breast mass (44%), breast pain (29%), and counseling on breast cancer (25%). The most frequent users were in their 3rd decade (55%), 4th decade (8%), and unknown age cases (23%). The average number of visitors on web was 454 per month. CONCLUSION: In near future, we believe that use of the web as an information source will grow rapidly and the most of the people in Korea will use internet. For that purpose, we should realize that virtual space is a reality, and we should use it as an effective technique for educating the public.

Toxicity of Bile Acids on Colon Cancer Cell Lines / 대한암학회지

PURPOSE: Cytotoxicity of the bile acids on colon cancer cell lines was studied to know which bile acid was most cytotoxic to colonic mucosal epithelium. We performed agarose gel electrophoresis whether this toxicity was caused by detergent effect of the bile acids or by apoptotic pathway. MATERIALS AND METHODS: HT29, LoVo, SW620 colon cancer cell lines were exposed to lithocholate, cholate, deoxycholate and chenodeoxycholate with 50, 100, 150, 200, 250, 300 pM as final concentration in DMEM culture media for short time (for 2 hours) and for long time (for 5 days). Agarose gel electrophoresis was performed on each colon cancer cell lines (HT29, LoVo, SW620, SW480) after 1, 2, 3, 4, 5 days exposure to deoxycholate with 150 pM concentration to detect intemucleosomal fragmentation. RESULTS: There was no toxicity after short time exposure in all bile acids concentration and in all colon cancer cell lines. Of the bile acids, deoxycholate was most toxic for all colon cancer cell lines. And DNA fragmentation was noticed after 2 days exposure with deoxycholate. Only LoVo cell line showed apoptotic DNA pattern after 4 days of exposure with deoxycholate. CONCLUSION: Bile acids (especially deoxycholate) are suggested to be possible agents to cause apoptosis in colonic mucosal epithelium.

Comparison of Polypropylene Mesh and Expanded Polytetrafluoroethylene Patch for Repair of Abdominal Wall Defects in Rat

BACKGROUND: Large abdominal wall defect resulting from trauma, invasive infection, tumor resection, or other causes continue to be major problems for patients and surgeons. The lack of sufficient tissue may require the insertion of prosthetic materials. This study compares the results of PPM mesh and e-PTFE patch for repairs of abdominal wall defects. METHODS: The anterior abdominal walls of Sprague-Dawley rats, including fascia, muscle, and peritoneum were removed. The defects were repaired with a PPM mesh or an e-PTFE patch. Animals were killed at 1, 2, 6, and 12 weeks after the operation, and the implant were excised along their margins and evaluated for gross and microscopic differences. RESULTS: Histological examination showed that PPM was progressively infiltrated by whorled disorganized collagen fiber, which became densely adherent to the mesh. In contrast, the e-PTFE was infiltrated by fine fibrils of collagen, which progressively penetrated the interstices of the material, binding it firmly to the tissue. One of the most serious complications associated with fascial closure with PPM was the development of visceral adhesions. CONCLUSIONS: e-PTFE patch material has a lower foreign body reaction, a lower infectability, and a lower rate of adhesion formation than PPM mesh.

The Occlusions of both Femoral Artery Bifucations by Myxomas: A case report

We describe a patient with an unusual cause of the occlusions of both femoral arteries by myxomas. A 41-year-old man presented with sudden onset of both leg pain and paresthesia. His hematological and cardiological status was normal. Lower peripheral angiography was performed and demonstrated thrombotic occlusion, both common femoral artery and superficial femoral and proximal portion of deep femoral artery. He was successfully treated with surgical and forgaty catheter extraction. Histologic finding was myxoma probably from cardiac origin. Cardiac investigations to determine the source of the myxoma, including 2-D echocardiography and Transesophageal echocardiogram (TEE) of the heart, failed to demonstrate residual myxoma in heart. No residual tumor or potential source of the tumor was found. The cause of both leg pain was the occlusions of the both common femoral arteries by myxomas. An entire cardiac tumor might have embolized with no detectable residual tumor in the heart; alternatively a myxoma might have originated as a primary tumor in the femoral artery.

Involvement of Oxidative Stress in Sodium Taurocholate-Induced Acute Necrotizing Pancreatitis in Rats

Oxidative radicals are regarded as a major factor in the pathogenesis of both acute and chronic pancreatitis. Because oxygen radicals react most readily with polyunsaturated fatty acids, resulting in peroxidation of lipids, several studies have been performed to determine the development of lipid peroxidation in pancreatitis. The purpose of this study was to evaluate the effects of free radicals and decision of the experimental model in acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 18 rats by retrograde injection into the bilopancreatic duct of 2%, 3%, and 5% sodium taurocholate. After a 12-hour observation time, the pancreas / the body weight, the serum amylase and the malondialdehyde content in tissue, as well as the reduced glutathione were measured in resected tissue samples. In addition, to determine the pathologic damage grade, tissue samples were examined by light microscopy. According to the amount of sodium taurocholate injected, the serum amylase and tissue malondialdehyde concentration were significantly increased. The reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. During the 12 hours after injection the pancreatic lesions were immediate and were characterized by interstitial edema, atrophy and extensive necrotic changes of the acinar cells, and hemorrhage. The pathologic damage grade increased according to the amount of sodium taurocholate injected. This study created an experimental model for studying the pathogenesis of acute necrotizing pancreatitis by using bile acid. In acute necrotizing pancreatitis, the increased levels of lipid peroxidation products in tissues and the change in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. Therefore, antioxidant treatment can reduce tissue damage, biochemical alterations, and extrapancreatic complications, thus improving the final outcome.

Expression of p53, bcl-2 Protein in Colorectal Cancer and Its Relationship to Pathologic Factor

PURPOSE: This study was undertaken to evaluate the correlation between p53, bcl-2 expression and pathologic factors stage, anatomic location, histologic grade, gross pattern, lymph node metastasis of the colorectal cancer. METHODS: Analysis were made on archival pathology tissue of 56 patients with colorectal cancer. The oncoproteins were localized using commerically available monoclonal antibodies : DO-7 for, p53 and clone 124 for bcl-2. RESULTS: P53 protein was detected in 53 out of 56(94.6%) adenocarcinomas of the colorectal cancer and the most frequently expressed patterns of immunoreactivity of p53 were strong in intensity in 40 cases(71.4%) and were diffuse in pattern in 39 cases(69.6%). Bcl-2 protein was detected in 34 out of 56(60.7%) adenocarcinomas of the colorectal cancer and the most frequently expressed patterns of immunoreactivity of bcl-2 were weak in intensity in 17 cases(30.3%) and were diffuse in pattern in 16 cases(28.6%). There was no correlation between p53, bcl-2 expression and Dukes' stage, anatomic location ,histologic grade, gross pattern of tumor, lymph node metastasis of the colorectal cancer. CONCLUSION: 53 mutation and bcl-2 expression are frequent event in human colorectal carcinoma as shown in this study, but p53 and bcl-2 protein expression is not significant independent predicator of aggressiveness and progression of colorectal cancers.

Differences in Serum CEA Level between Colon and Rectal Cancer

We investigated whether there is differences in serum level of carcinoembryonic antigen (CEA) between patients with colon and rectal cancer. Preoperative serum levels of CEA was determined in 65 patients with colon cancer and in 88 patients with rectal cancer. Cut-off value recommended by manufacturers is 5 ng/ml for CEA. At the recommended cut-off levels for CEA, overall sensitivity of CEA was 43.1 percent for colon and 42.0 percent for rectal cancer. In colon cancer CEA was elevated in 38.4, 46.2, 60 percent of patients with Dukes Stages B, C, and D, respectively. In rectal cancer CEA was elevated in 12.5, 31.6, 44.8, 84.6 percent of patients with Dukes Stages A, B, C, and D, respectively. In Stages B, and C, sensitivity of CEA was higher in colon than in rectal cancer, but the difference was not significant. In Stages D, sensitivity of CEA was higher in rectal cancer than in colon cancer, but the difference was not significant. In overall stages sensitivity of CEA was higher in colon than in rectal cancer, but the difference was not significant. The difference was not significant either in overall or in different stages of colon and rectal cancer.

Bacteriologic Study and Prophylactic Antibiotics in the Acute and Complicated Appendicitis

This prospective study was performed to determine the effective antibiotics for use in treating acute appendicitis patients during the perioperative period. To identify the sensitive antibiotics, the peritoneal fluid was cultured during operation. Also, wound infection was defined as pus or serous discharge in the wound or when we opened the wound under suspicious of a wound problem. The results were obtained as follows: 1) A total of 138 cases treated during the two years from January 1995 to December 1996 were examined; 84 of them (60.87%) were found to have positive peritoneal fluid cultures, of which 29 (34.52%) were monomicrobial and 55 (65.48%) were polymicrobial. 2) The most common species were Escherichia coli (73.81%), Bacteroides (32.14%), Klebsiella (16.67%), Pseudomonas (9.52%), and Streptococcus (9.52%). 3) In the sensitivity test, the most sensitive drugs were aminoglycosides and cefotaxime. 4) Infectious complications, which developed in 27 (19.6%) patients, were wound infection and intraabdominal abscess. 5) The average length of stay for all patients 9.9 days (range: 3 to 32 days). 6) The common organisms curtured from the complication cases were E. coli and Bacteroides.

Cytosolic Glutathione S-Transferase Change after Deoxycholate Exposure in Colon Cancer Cell Lines

PURPOSE: Bile acids (especially deoxycholate) was known to be toxic and mutagenic on colon epithelium. They proposed at least four mechanisms for the bile acid toxicity. It is the one of these mechanisms that bile acid inhibits the xenobiotic metabolizing enzyme activity (esp glutathione S-transferase, GST). So we measured the cytosolic GST level of colon carcinoma cell lines after deoxycholate exposure whether or not the deoxycholate lowered the cytosolic GST activity. METHODS: Three colon cancer cell lines (LoVo, SW480, HT29) were used for this study. We calculated the cellular toxicity by MTS method. And cytosolic GST activity was measured according to the method as Habig described. For total GST activity, 2.5 mM 1-chloro-2,4-dinitrobenzene was used for substrate, and measured as absorbance in 340 nm. RESULTS: Basal cytosolic GST level for LoVo, SW480, HT29 cell line was 514.59+/-27.01, 291.63+/-38.44 and 344.58+/-47.92 nmol/min/mg cytosol protein. GST level did not changed significantly after 5 days culture without DCA. But GST level was decreased significantly to 128.63+/-21.35, 134.33+/-41.76 and 163.10+/-22.73 nmol/min/mg cytosol protein each cell line after 5 days deoxycholate exposure (p<0.005). CONCLUSION: Cytosolic GST level was lowered significantly after deoxycholate exposure for 5 days. One of the mechanisms of bile acid toxicity for colon cancer cell is proposed to inhibit cytosolic GST activity.

Expression of hMSH2, hMLH1 Protein in Sporadic Colorectal Cancer and Corresponding Normal Tissue

PURPOSE: DNA mismatch repair gene is responsible for hereditary nonpolyposis colorectal cancer. But it is not well known its role in sporadic colorectal cancer patients. We analysed normal hMSH2, hMLH1 protein expression in colorectal adenocarcinoma tissues and corresponding normal tissues to find out the role of mismatch repair gene in sporadic colorectal cancer by Western blotting. METHODS: Normal hMSH2 and hMLH1 protein expression was studied on 25 colorectal cancer and corresponding normal tissue by Western blot with hMSH2 and hMLH1 monoclonal antibody. Normal protein band was expressed on 100 kD in hMSH2 and 87 kD in hMLH1. SW480 and LoVo cell line was used as positive and negative control for hMSH2 and LoVo and SW480 as positive and negative for hMLH1. And we analysed the relation between the hMSH2, hMLH1 protein expression and clinicopathological parameters. RESULTS: It was 2 cases (8%) that both hMSH2 and hMLH1 protein expression was not observed. Three cases (12%) were negative for hMSH2 and 2 cases (8%) for hMLH1. One or both hMSH2, hMLH1 protein expression was not observed in 7 cases (28%) in total. There was no correlation for proximal occurrence (25% vs 35%), young age (37.5% vs 23.5%) and lymph node metastasis (50% vs 47%). But poorly and mucinous differentiation was regarded as having relation with negative expression of hMSH2 and hMLH1 (50% vs 17.6%) but not significant statistically. CONCLUSION: Sporadic colorectal cancer with negative expression of normal hMSH2 and hMLH1 protein showed no relation to younger age, proximal site preference and lymph node metastasis. But it was suggested that mismatch repair gene protein was involved in cancer cell differentiation in sporadic colorectal cancer.

bcl-2 and p53 Gene Expression in Colonic Adenoma and Carcinoma / 대한암학회지

PURPOSE: Recently, it is suggested that the inhibitian of apoptosis is associated with tumorigenesis of colon. Bcl-2 gene is an important inhibitory regulator of apoptosis, and bcl-2 acts antagonistly with the wild type p53 gene, one of the tumor suppressor genes, in apoptosis. To detnmine the role of bcl-2 and p53 gene in colonic tumorigenesis, we performed the study. MATERIALS AND METHODS: We tested the tissue obtained by polypectomy and surgical resection by immunohistochemical staining for Bcl-2 and p53. RESULTS: We found that in normal colonic tissue, the Bcl-2 was sparcely expressed, and the p53 was expressed sporadically. The rate of positivity of staining was below 5%. However, in colonic adenoma and colon cancer tissue, Bcl-2 and p53 were expressed more than in nonnal colonic tissue(p<0.05). (Scoring in Colonic adenoma: Bcl-2 6.2+/-1.1, p53 5.7+/-1.0; Scoring in Colonic carcinoma: Bcl-2 4.7+/-1.0, p53 8.3+/-0.9) CONCLUSION: Our results suggested that the bcl-2 and p53 play an important role in colonic tumorigenesis.

Small Flat Adenocarcinoma of the Colon Arising From Familial Adenomatous Polyposis Patient: Suggesting de novo Origin

Most adenocarcinomas of the colorectum arise in a visible benign precursor lesion, the adenoma, which is a monoclonal proliferation of dysplastic nonmalignant epithelial cells. Adenoma-adenocarcinoma sequence has been represented as the predominat pathogenetic pathway. But a small flat depressed colon cancer is characterized by non-polypoid growth pattem with no association of adenomatous tissues, which has tendency to early submucosal invasion and lymph node metastasis even in very small lesion (<10 mm). It supports de novo carcinogenesis of colorectal cancer, although most colorectal cancerarise in pre-existing adenoma. We report a case of small float colon adenocarcinoma arising in normal colonic epithelium rather than adenomatous polyp in familial adenomatous polyposis syndrome.

In vivo Assessment for the Antioxidant Activity of the Calcium Channel Blocker Nicardipine in 3% Sodium-Taurocholate-induced Acute Pancreatitis

BACKGROUND: Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unkown. Cellular calcium, a key function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis. The aim of this study is to evaluate the role of cellular calcium and therapeutic effect of administering the Ca++ channel blocker nicadipine as an antioxidant. METHOD:Nicardipine, known to be a calcium channel blocker and a most potent antioxidant, was wed as a pretreatment 1 hour before induction of pancreatitis by intraductal infusion of 3% sodium taurocholate or as a post-treatment 1 hour after induction of aucte pancreatitis by retrograde infusion of sodium taurocholate. The net weight of the pancrease, the amounts of s-amylse, GSH and MDA in the pancreatic tissue, and the histologic damage were examined 12 hours after the induction of pancreatitis. RESULTS: Nicardipine administration ameliorated pancreatic edema and reduced the amount of s-amylase compare to untreated necrotizing pancreatitis group. Also, pre- or post-treatment with nicardipine had beneficial protective effect with respect to free radical-induced injury; in particular, pre-treatment with nicardipine was much better. With respect to the histologic findings, pancreatic necrosis, hemorrhage, and neutrophil infiltration were prominent in the necrotizing group, however, in the group treated with nicardipine, the necrosis and hemorrhage were ameliorated remarkably. CONCLUSION:The free oxygen radicals and the intracellular calcium influx were major elements in the pathogenesis of acute pancreatitis, and nicardipine ameliorated pancreatic necrosis and hemorrage and exerted an antioxidant effect. The administration of nicardipine should be considered in the early stage of pancreatitis or in case of risk of pancreatitis.

Gastrointestinal Injuries from Blunt Abdominal Trauma

Hollow visceral injuries are far less commom in blunt abdominal trauma than in penetrating abdominal trauma. From June 1994 to Sep. 1996, we treated 46 patients with blunt injuries to the gut, defined as perforation or devascularization. Thirty five patients(76.1%) were injured in motor vehicle collisions. Of these, 22 were not using constraints; 13 were wearing seat belts. Small bowel injuries were the most frequent injuries, followed by colonic injuries, duodenal injuries, rectal injury and gastric perforation. Mortality rates were the lowest in small bowel injuries(11.1%) and higher in less common colonic(22.2%) and duodenal(20.0%) injuries. Except for those patients with perforations of the small bowel, most patients had associated injuries to the head, chest or abdominal solid organs that were largely responsible for morbidity and mortality. Injuries to the abdominal hollow viscera are unusual following blunt trauma, but are the result of very high energy truncal trauma and are associated with multiple additional injuries. Most alert patients had physical findings suggestive of peritoneal irritation, but when diagnostic testing was necessary, peritoneal lavage was superior to CT scanning ( false negative=10.5% versus 88.5% respectively). A high index of suspicion is necessary to avoid diagnostic delays that can lead to severe complications and death.

hernia Repair in Patients with Ascites

The hospital records of 7 patients with ascites and hernias ( 6 patients had inguinal, 1 patient had umbilical) were reviewed restrospectively. The causes of ascites were liver cirrhosis in 7 patients. Among the 7 patients with liver cirrhosis and ascites, 6 were Child C and 1 was Child B. Among the 7 patients, 5 of them underwent ascites control with diuretics and 2 underwent ascites control with large volume paracentesis. All patients underwent hernia repair as elective surgery. The only complication was primary peritonitis because of insufficient control during the preoperative period, and there were no perioperative deaths or ascites leaks. All patients were available for follow-up. In this group, recurrence did not occurr for a mean 14.3 months after repair. From this retrospective study, we suggest that surgeons should repair hernias with ascites if patients suffer from their hernias because elective hernia repair can be performed safely without any complications or ascites leaks. Child C hepatic dysfunction or uncontrolled ascites can not be contraindications.