Acute acalculous cholecystitis caused by gallbladder metastasis due to the peritoneal dissemination of gastric cancer: A case report.

INTRODUCTION AND IMPORTANCE: Acute acalculous cholecystitis (AAC) is associated with a high mortality rate. AAC caused by metastasis to the gallbladder is rare. We report a case of AAC caused by gallbladder metastasis due to the peritoneal dissemination of gastric cancer. CASE PRESENTATION: An 84-year-old male visited our hospital because of epigastric pain. Ultrasonography and computed tomography revealed swelling and thickening of the gallbladder wall, but stones were not observed in the gallbladder. We performed emergency surgery with a diagnosis of acute cholecystitis. Laparoscopy revealed the presence of many nodules around the abdominal cavity including the hepatoduodenal ligament. Inflammation of Calot's triangle was severe, so we performed subtotal cholecystectomy. We also resected one of the peritoneal nodules. Macroscopically, there were no stones in the gallbladder and histopathological examination revealed acute cholecystitis and existence of adenocarcinoma involving the subserosa of the gallbladder wall and the resected peritoneal nodule. After surgery, esophagogastroduodenoscopy revealed Borrmann type II lesions at the antrum and gastric biopsy showed adenocarcinoma. He was diagnosed with advanced gastric cancer with peritoneal dissemination. His postoperative course was good. CLINICAL DISCUSSION: The cases of AAC caused by gallbladder metastasis have been little reported in the literature. This case is advanced gastric cancer with peritoneal dissemination and AAC was thought to be caused by peritoneal dissemination from operative and histopathological findings. We successfully treated this rare case of AAC with laparoscopic surgery. CONCLUSION: Although metastasis to the gallbladder is rare, it is necessary to be aware of this possibility when treating AAC.

Prognostic significance of p16(INK4a) hypermethylation in non-small cell lung cancer is evident by quantitative DNA methylation analysis.

BACKGROUND: p16(INK4a) is a tumor suppressor gene frequently inactivated by aberrant promoter hypermethylation. In the present study, p16(INK4a) methylation was evaluated in non-small cell lung cancer (NSCLC) using a quantitative assay and the clinical significance of the methylation was explored. MATERIALS AND METHODS: A total of 244 tumor samples from formalin-fixed paraffin-embedded archives were examined in this study. p16(INK4a) methylation was analyzed by the fluorescence-based, real-time methylation-specific PCR assay, MethyLight. The quantitative methylation value was expressed as the percentage of methylated reference (PMR). RESULTS: The median level of p16(INK4) methylation was 0.55 PMR (range 0.00-503.4). The p16(INK4) methylation value was significantly higher in males (p = 0.005) and in squamous cell carcinoma (p = 0.018). Prognostic analysis using the Cox proportional hazard model showed that the p16(INK4a) methylation value was a significant prognostic factor (odds ratio, 1.005; 95% CI, 1.003 to 1.008; p < 0.0001). The p16(INK4a) methylation value remained a significant prognostic factor (p = 0.0004) in multivariate analysis including age, gender, histological type and clinical stage. Specimens were then classified into hypermethylated or non-hypermethylated groups based on the p16(INK4a) methylation value using various cut-offs from 1 to 100 PMR. There was no significant difference in prognosis between the two groups using a cut-off value of 1 PMR. On the other hand, there was a significant difference using 6 PMR or more as the cut-off value (p < 0.01). CONCLUSION: These results provide clear evidence for the prognostic significance of p16(INK4a) methylation in NSCLC using quantitative DNA methylation analysis. Careful assessment of DNA methylation is needed because qualitative methylation analysis may overestimate low levels of methylation, which have less clinical significance.

The profile of hMLH1 methylation and microsatellite instability in colorectal and non-small cell lung cancer.

Microsatellite instability (MSI) is caused mainly by dysfunction of hMLH1, where aberrant hypermethylation (HM) of its promoter region is involved. Previously, we suggested that HM in the proximal region of the hMLH1 promoter plays a critical role in progression of gastric cancer with MSI and this specific region should be analyzed for diagnostic use of hMLH1 HM. We expanded the analyses of hMLH1 HM and MSI phenotype to sporadic colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) to further evaluate the diagnostic value of hMLH1 HM. A total of 174 CRC and 94 NSCLC samples were used for hMLH1 methylation analysis by real-time methylation-specific PCR. Methylation levels were measured in three distinct regions of the promoter, designated as hMLH1-A, hMLH1-B, and hMLH1-C from distal to proximal. MSI phenotype was determined using five microsatellite markers, BAT25, BAT26, D2S123, D5S346, and D17S250. Methylation profile of the hMLH1 promoter varies between CRC and NSCLC. High methylation levels were observed in a group of CRC samples. Consequently, three patterns of methylation in the hMLH1 promoter regions were found: 1) low methylation level in all regions, 2) high methylation level in hMLH1-A with low methylation level in hMLH1-C, 3) high methylation level in all regions. In contrast, only one NSCLC showed high methylation level in hMLH1-A. Of the 134 CRCs examined, 14 (10.4%) showed MSI phenotype. No MSI phenotype was found in the initial 80 NSCLCs analyzed. Eight (57.1%) of 14 CRC with MSI showed HM in hMLH1-C, which was linked exclusively with MSI phenotype. However, the HM in hMLH1-A or -B was not sufficient for MSI. CRC with MSI phenotype was significantly more frequent in older patients and in the proximal colon, and was more evident in cases with hMLH1-C HM. The results suggested that hMLH1 HM cannot be used as an alternative diagnostic marker of MSI phenotype in sporadic CRC and NSCLC. CRC with MSI might have clinicopathologically distinct subgroups according to hMLH1-C HM status. The observed profiles of hMLH1 methylation and MSI in gastric cancer, CRC, and NSCLC were quite different from each other, facilitating the better understanding of the pathogenesis of these cancers.

[Weekly administration of low-dose paclitaxel for advanced or metastatic breast cancer].

The activity and toxicity of a weekly infusion of low-dose paclitaxel was studied. Twelve patients with metastatic or advanced breast cancer received paclitaxel (80 mg/m2 over 1 h) every week. Administration was continued for 6 weeks with two weeks rest until disease progression or limiting toxicity. Dexamethasone 20 mg, diphenhydramine 50 mg, and ranitidine 50 mg were given prior to each dose of paclitaxel. Six patients had received prior standard CMF therapy, and four patients had received CMF and docetaxel therapy. Two patients had not received prior therapy. The overall response rate was 58% with 17% complete responses and 42% partial responses. Responses were observed in both patients without prior therapy, and in five of 10 (50%) with prior therapy. Grade 3/4 neutropenia occurred in one patient; febrile neutropenia was not observed. There was no neuropathy or hypersensitivity. Weekly paclitaxel is active and well tolerated in patients with metastatic or advanced breast cancer. This schedule allows a high cumulative dose of paclitaxel without major myelo- or neurotoxicity. This weekly regimen deserves further exploration.