Teni Godai

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease

BackgroundThe guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.Methods144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.ResultsPatients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.ConclusionsOur study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

Perivascular epithelioid cell tumor of the rectum: report of a case and review of the literature

We report a case of perivascular epithelioid cell tumor arising in the rectum of a 55-year-old woman. The tumor was treated by transanal endoscopic microsurgery. After 1 year follow-up, the patient is alive with no radiologic or endoscopic evidence of recurrence. Perivascular epithelioid cell tumor is a rare mesenchymal tumor characterized by co-expression of melanocytic and smooth muscle markers. This rare tumor can arise in various organs, including the falciform ligament, uterus, uterine cervix, liver, kidney, lung, breast, cardiac septum, pancreas, prostate, thigh, and gastrointestinal tract. Perivascular epithelioid cell tumor of the gastrointestinal tract is very rare, with only 23 previously reported cases. We review the literature on perivascular epithelioid cell tumors arising in the gastrointestinal tract.

Rare MDM4 gene amplification in colorectal cancer: The principle of a mutually exclusive relationship between MDM alteration and TP53 inactivation is not applicable

MDM4, a homolog of MDM2, is considered a key negative regulator of p53. Gene amplification of MDM4 has been identified in a variety of tumors. MDM2 or MDM4 gene amplification is only associated with the wild-type TP53 gene in retinoblastomas, thus the amplification of the two genes is mutually exclusive. Previously, we demonstrated that MDM2 amplification and TP53 alteration were not mutually exclusive in colorectal cancer, and we identified a subset of colorectal cancer patients without alterations in either the TP53 or the MDM2 gene. In this study, we investigated the gene amplification status of MDM4 in the same set of colorectal cancer cases. Unexpectedly, MDM4 amplification was rare, detected in only 1.4% (3 out of 211) of colorectal cancer cases. All the three gene-amplified tumors also harbored TP53-inactivating mutations. This contradicts the simple mutually exclusive relationship observed in retinoblastomas. Surprisingly, two of the three MDM4-amplified tumors also demonstrated MDM2 amplification. Paradoxically, the MDM4 protein levels were decreased in the tumor tissue of the gene-amplified cases compared with levels in the matched normal mucosa. We speculate that MDM4 might play a role in colorectal carcinogenesis that is not limited to negative regulation of p53 in combination with MDM2. The functional significance of MDM4 is still unclear and further studies are needed.

Postoperative CA19-9 and Glasgow prognostic score to predict early recurrence and poor prognosis in pancreatic cancer patients undergoing adjuvant chemotherapy after surgery.

198 Background: Despite proven benefit of adjuvant chemotherapy in pancreatic cancer patients, earlyrecurrenceoccursinaconsiderablerate. Therefore, outcomeprediction in these patients remains a challenge. The aim of this study was to determine whether Glasgow Prognostic Score (GPS) and CA19-9 could predict early recurrence in patients undergoing adjuvant chemotherapy after surgery. Methods: 67 pancreatic ductal adenocarcinoma (PDAC) patients underwent curative resection and received adjuvant chemotherapy with gemcitabine after surgery at Kanagawa Cancer Center between 2007 and 2012.The GPS, CA19-9(measured prior to adjuvant therapy) and other clinicopathological factors were retrospectively reviewed. The GPS was calculated from CRP and albumin as follows: patients with both an elevated CRP level (>0.5mg/dl) and hypoalbuminemia (<3.5g/dl) were allocated a score of 2, patients with only one of these biochemical abnormalities were allocated a score of 1, and patients with neither of these abnormalities were ...

The clinical significance of S100A10 in pancreatic cancer.

194 Background: S100A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. They regulate a number of cellular processes such as cell cycle progression and differentiation. The objective of this study is to clarify the clinical significance of S100A10 in patients with pancreatic cancer. Methods: A total of 48 pancreatic adenocarcinoma tissues from patients underwent curative surgery were enrolled. Double 2-mm core tissue microarrays were made from paraffin-embedded pancreatic cancer samples and examined by immunohistochemistry for S100A10 protein. The correlations of expression level and clinicopathological outcome including recurrence free survival (DFS) were analyzed. Results: Expression level of the S100A10 protein in cytoplasm was categorized as overexpressed or others according to the baseline expression level in normal pancreatic duct. Overexpression of S100A10 protein was found in 9 of 48 (16.7%) cases. Statistical analysis revealed that related factor was dist...