Clinical and molecular analysis of hereditary non-polyposis colorectal cancer in Chinese colorectal cancer patients

AIM： To analyze the frequency of hereditary non-polyposis colorectal cancer （HNPCC） in Chinese colorectal cancer （CRC） patients, and to discuss the value of microsatellite instability （MSI） and/or immunohistochemistry （IHC） for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS： The Amsterdam criteria Ⅰ and Ⅱ （clinical diagnosis） and/or germline hMLHI/hMSH2 mutations （genetic diagnosis） were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS： From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients （5.7%） from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION： The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable prescreening tests for hMLHI/hMSH2 germline mutations in families suspected of having HNPCC.

Contrast-enhanced ultrasonography assessment of gastric cancer response to neoadjuvant chemotherapy

AIM:To quantitatively assess the ability of double contrast-enhanced ultrasound(DCUS) to detect tumor early response to pre-operative chemotherapy.METHODS:Forty-three patients with gastric cancer treated with neoadjuvant chemotherapy followed by curative resection between September 2011 and February 2012 were analyzed.Pre-operative chemotherapy regimens of fluorouracil + oxaliplatin or S-1 + oxaliplatin were administered in 2-4 cycles over 6-12 wk periods.All patients underwent contrast-enhanced computed tomography(CT) scan and DCUS before and after two courses of pre-operative chemotherapy.The therapeutic response was assessed by CT using the response evaluation criteria in solid tumors(RECIST 1.1) criteria.Tumor area was assessed by DCUS as enhanced appearance of gastric carcinoma due to tumor vascularity during the contrast phase as compared to the normal gastric wall.Histopathologic analysis was carried out according to the Mandard tumor regression grade criteria and used as the reference standard.Receiver operating characteristic(ROC) analysis was used to evaluate the efficacy of DCUS parameters in differentiating histopathological responders from non-responders.RESULTS:The study population consisted of 32 men and 11 women,with mean age of 59.7 ± 11.4 years.Neither age,sex,histologic type,tumor site,T stage,nor N stage was associated with pathological response.The responders had significantly smaller mean tumor size than the non-responders(15.7 ± 7.4 cm vs 33.3 ± 14.1 cm,P < 0.01).According to Mandard's criteria,27 patients were classified as responders,with 11(40.7%) showing decreased tumor size by DCUS.In contrast,only three(18.8%) of the 16 non-responders showed decreased tumor size by DCUS(P < 0.01).The area under the ROC curve was 0.64,with a 95%CI of 0.46-0.81.The effects of several cut-off points on diagnostic parameters were calculated in the ROC curve analysis.By maximizing Youden's index(sensitivity + specificity-1),the best cut-off point for distinguishing responders from non-responders was determined,which had optimal sensitivity of 62.9% and specificity of 56.3%.Using this cut-off point,the positive and negative predictive values of DCUS for distinguishing responders from non-responders were 70.8% and 47.4%,respectively.The overall accuracy of DCUS for therapeutic response assessment was 60.5%,slightly higher than the 53.5% for CT response assessment with RECIST criteria(P = 0.663).Although the advantage was not statistically significant,likely due to the small number of cases assessed.DCUS was able to identify decreased perfusion in responders who showed no morphological change by CT imaging,which can be occluded by such treatment effects as fibrosis and edema.CONCLUSION:DCUS may represent an innovative tool for more accurately predicting histopathological response to neoadjuvant chemotherapy before surgical resection in patients with locally-advanced gastric cancer.

Surgical resection of advanced gastric cancer following trastuzumab/oxaliplatin/capecitabine combination therapy

Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates. To improve long-term outcomes, perioperative chemotherapies are combined with surgery. Human epidermal growth factor receptor 2 (HER2) overexpression had been noted in gastric cancer; therefore, trastuzumab has been used occasionally in this setting. A 63-year-old male Chinese patient, who was diagnosed with adenocarcinoma in the gastric antrum, as well as lymph node metastases along the left gastric and hepatic artery, and left adrenal area, was admitted to our hospital. HER2 expression was positive, and cluster amplification was detected in a fluorescence in situ hybridization assay. The patient received three cycles of a neoadjuvant trastuzumab/oxaliplatin /capecitabine regimen. He subsequently underwent distal gastrectomy, D2+ lymphadenectomy, left adrenalectomy, cholecystectomy and Billroth II anastomosis. Treatment was continued with another five postoperative cycles of the same medication and trastuzumab application for 1 year. No recurrence has been observed 18 mo after the operation. Trastuzumab as perioperative and adjuvant medication, in combination with oxaliplatin and capecitabine for a HER2-overexpressing advanced gastric adenocarcinoma, led to recurrence-free survival of at least 18 mo after surgery.

Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6

AIM: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A recepto (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro . METHODS: HSCs were derived from the livers of adul male Sprague-Dawley rats. IL-6 expression was evalu ated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated pro tein kinases (MAPK) and extracellular regulated pro tein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting.RESULTS: IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of IL17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P < 0.01). Moreover, lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P < 0.01). Lentiviral-mediated IL17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.

Ileocecal endometriosis and a diagnosis dilemma: A case report and literature review

Bowel endometriosis affects between 3.8% and 37% of women with endometriosis. The evaluation of symptoms and clinical examination are inadequate for an accurate diagnosis of intestinal endometriosis. We describe the case of a 41-year-old woman who presented to our hospital because of six months of recurrent abdominal pain, vomiting and diarrhea, without previous history of bowel disease. Physical examination revealed a palpable 3 cm × 5 cm mass in the right lower quadrant abdomen. Laboratory tests showed slightly elevated levels of CA19-9 and CA125. Small bowel computer tomography scanning revealed an ileocecal mass with bowel wall thickening and luminal narrowing. Small bowel endoscopy identified a deep longitudinal ulcer and mucosal edema in the distal ileum. All these findings supported the diagnosis of Crohn's disease. The patient underwent a laparotomy, which identified a 5 cm × 5 cm ileocecal mass with severe mucosal edema and luminal stricture in the distal ileum. Histopathological examination confirmed a diagnosis of ileocecal endometriosis without other areas involved. After oneyear follow-up, there was no recurrence of the symptoms.

Gorham-Stout syndrome in China's Mainland:a case series of 67 patients and review of the literature

Objective:Gorham-Stout syndrome (GSS) is a rare disorder of uncertain etiology and unpredictable prognosis. This study aims to present a comprehensive understanding of this rare entity. Methods:A literature search in PubMed and three Chinese databases was performed to screen histologically proven GSS cases among Chinese residents in the mainland. We analyzed the patients' clinical characteristics, the value of different treatment modalities and their influence on the clinical outcome. Results:Sixty-seven cases were finally enrolled. There were 43 men (64.2%) and 24 women (35.8%). The mean age at diagnosis was 28 years (1.5-71 years). The most common clinical symptoms included pain (n=40, 59.7%), functional impairment (n=13, 19.4%), and swelling (n=12, 17.9%). The radiographic presentation of 37 cases (55.2%) was disappearance of a portion of the bone. The others presented as radiolucent foci in the intramedullary or subcortical regions. A total of 42 cases provided data on therapy, these included surgery (n=27, 40.3%), radiation therapy (n=6, 9.0%), surgery combined with radiation therapy (n=2, 3.0%), and medicine therapy (n=7, 10.4%). For 30 of these 42 cases, follow-up data were available:21 cases had the disorder locally controlled and 9 had a symptom progression. Fortunately, the disease is not fatal in the majority of cases. Conclusions:GSS has no specific symptoms and it should be taken into consideration when an unclear massive osteolysis occurs. The efficacies of different treatment modalities are still unpredictable and further research is required to assess the values of different treatments.