Expression of altered retinoblastoma protein inversely correlates with tumor invasion in gastric carcinoma

INTRODUCTION Cellular proliferation normally follows an orderly progression through the cell cycle, which is governed by protein complexes encoding various genes. Malignant transformation results from a series of genetic alterations that lead to aberrant …     

Platelet count correlates with stage and predicts survival in melanoma

Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality. Using multivariable analysis, patients with thrombocytosis around time of diagnosis were more likely to present with distant metastasis (Prevalence Ratio 3.5, 95% CI 2.35–5.22). In patients with metastatic disease and in all stages combined, thrombocytosis predicted decreased 5-year overall survival in univariate and multivariable analysis, and this was most pronounced during the first year after diagnosis. Finally, we show that mice with thrombocytopenia due to the lack of heat shock protein gp96 in their megakaryocytes are protected from melanoma dissemination to the lungs. These findings are concordant with preclinical studies showing a role for platelets in cancer metastasis and suppression of antitumor immunity, further supporting targeting platelets as an adjuvant to immunotherapy in melanoma.     

Adenosquamous carcinoma of the gallbladder with tumor thrombus in left portal trunk

We report a surgically resected case of adenosquamous carcinoma of the gallbladder accompanied by portal tumor thrombosis, which is regarded as a rare complication. A 73-year-old man was admitted to our hospital because of epigastralgia. Preoperative examinations led to a diagnosis of advanced gallbladder carcinoma with liver metastasis, and operation was performed. Since intraoperative ultrasonography showed a tumor thrombus in the left main portal trunk originating from the metastatic lesion in the left medial segment of the liver, extended left lobectomy with extrahepatic bile duct resection and lymph node dissection was performed, instead of right trisegmentectomy, as proposed preoperatively. Histological examination revealed adenosquamous carcinoma of the gallbladder with medullary growth that was similar to the hepatocellular carcinoma, most notably in the metastatic lesion of the liver and in the portal tumor thrombus. We discuss the relation between portal tumor thrombosis and medullary tumors, and note the atypical operative method employed.     

Adenomyomatosis of the gallbladder with subserosal fatty proliferation: CT findings in two cases.

Adenomyomatosis of the gallbladder is frequently seen in ordinary operative specimens. Subserosal fat may proliferate in the presence of adenomyomatosis, but the amount of subserosal fat may be quite variable. Typical and atypical computed tomographic (CT) findings in two cases of adenomyomatosis with subserosal fatty proliferation of the gallbladder are presented. The thick fatty layer surrounding the thickened gallbladder wall with intramural diverticula and stones, typical of CT findings, was seen in one case, and fat interspersed in the periphery of the thickened gallbladder wall without intramural stones, atypical of CT findings, was seen in a second case.     

HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.     

胆囊癌组织CDl5和Bcl-2的表达及相关性研究

研究CD15抗原和bcl- 2癌基因蛋白产物在胆囊癌组织中的表达与组织类型、病理分级和转移的关系 ,并探讨CD15与癌基因蛋白表达的相关性。应用微波 -SP免疫组化法 ,检测 45例胆囊腺癌、17例胆囊腺瘤和10例慢性胆囊炎组织中CD15和bcl 2的表达水平。在胆囊癌中CD15和bcl 2阳性表达率分别为 71 1%和 6 0 %。其表达阳性率在胆囊癌中均明显高于胆囊腺瘤 (P <0 0 5 ) ,并与胆囊癌的组织类型、病理分级和转移密切相关 (P<0 0 5 )。CD15表达与bcl 2表达呈明显相关联。CD15和bcl 2均是胆囊癌高度恶性和预后不良的重要生物学指标。胆囊癌CD15表达与bcl 2蛋白表达具有相互协同作用可能     

Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma

OBJECTIVES: The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases capable of degrading the extracellular matrix and play important roles in malignancies. We evaluated the expression of four MMPs in esophageal squamous cell carcinoma (ESCC), and assessed the association between MMP expression and clinicopathologic characteristics and disease-free survival time. METHODS: We evaluated MMP1, MMP7, MMP9, and MMP13 expression in tissues from 208 patients with ESCC using immunohistochemistry (IHC), and correlated MMP expression to clinicopathologic characteristics and disease-free survival time. To confirm MMP9 expression at different levels, we simultaneously performed RT-PCR, Western blotting, and IHC on tissues from a separate cohort of 23 patients with ESCC. RESULTS: IHC analysis showed that 63.0%, 41.8%, 49.0%, and 32.2% of 208 ESCC samples were positive for MMP1, MMP7, MMP9, and MMP13, respectively. MMPs were strongly expressed in the cytoplasm of cancer cells, especially in the invasive margin, and weakly expressed in stromal cells. No immunostaining was detected in non-cancerous esophageal mucosa. MMP9 expression was positively associated with poor tumor cell differentiation (p= 0.001), vessel permeation (p= 0.027), and lymph node metastasis (p= 0.027). MMP9 expression was a negative, independent predictor of disease-free survival time (Hazard ratio, 1.470; 95% CI, 1.105 approximately 1.955; p= 0.008). The expression of MMP7 (median survival time: 23 months for MMP7 positive patients, >77 months for MMP7 negative patients; p= 0.001) and MMP13 (median survival time: 18 months for MMP13 positive patients, 39 months for MMP13 negative patients; p= 0.014) correlated negatively with disease-free survival in relatively early stage ESCC patients. Co-expression of MMP7, MMP9, and MMP13 in relatively early stage ESCC samples identified patients with a poor prognosis (13 months median survival time) compared to those lacking MMP7, MMP9, and MMP13 expression (58 months median survival time, p < 0.001). CONCLUSIONS: MMP9 expression is a negative, independent prognostic factor in ESCC and correlates with tumor cell differentiation, vessel permeation, and lymph node metastasis. MMP7, MMP9, and MMP13 may function in early stage ESCC, and their co-expression predicts poor outcome for relatively early stage ESCC patients.     

Universal safe procedure of laparoscopic cholecystectomy standardized by exposing the inner layer of the subserosal layer (with video)

An incorrect approach to the critical view of safety can cause bile duct and/or vascular injury. However, only superficial anatomical features have been proposed as surgical landmarks to initiate laparoscopic cholecystectomy (LC) safely in previous reports. Accordingly, we have proposed a novel surgical anatomical definition of the gallbladder wall, in which the subserosal (SS) layer is divided into the inner layer of the SS (SS‐Inner) layer consisting of vasculature and fibrous tissue, and the outer layer of the SS (SS‐Outer) layer consisting of abundant fat tissue. By dissecting the gallbladder along the SS‐Inner layer after exposure at a safe region, bile duct and/or vascular injury can be avoided, even in cholecystitis cases. Furthermore, recognition of this surgical anatomy reveals several aspects. In cholecystitis cases associated with severe fibrotic change, completion of LC by dissecting along the SS‐Inner layer is impossible, resulting in abandonment of regular LC. An abscess in the liver bed associated with acute cholecystitis usually forms in the SS‐Outer layer, thus, the gallbladder can be dissected easily. In the dome‐down technique, the right hepatic duct is endangered by whole‐layer dissection, in which the SS‐Outer layer is also removed. The proposed procedure should become the universal standard for LC.     

Long-term survival of a patient with advanced adenosquamous carcinoma of the gallbladder after radical resection

Patients with adenosquamous carcinoma of the gallbladder tend to present with a bulky tumor that frequently displays involvement with adjacent organs, and diagnosis is usually made at an advanced stage. This may contribute to the poor prognosis of patients with adenosquamous carcinoma of the gallbladder compared to patients with adenocarcinoma. We present herein a patient with advanced adenosquamous carcinoma of the gallbladder who is doing well with no evidence of recurrence more than 5 years after radical resection. A 72-year-old woman complaining of generalized fatigue and loss of appetite was referred to our hospital with suspected cholelithiasis, following ultrasonography done at another hospital. On admission, abdominal ultrasonography and computed tomography revealed an irregularly shaped solid mass extending from the fundus of the gallbladder, and invasion of the stomach was strongly suspected. Gallbladder carcinoma was diagnosed, and radical resection, including partial gastrectomy, was performed. Histopathologically, adenosquamous carcinoma was diagnosed, and it was graded as si, hinf0, binf0, pv0, a0, t4, n0, and stage IVa.     

The critical view of safety in laparoscopic cholecystectomy is optimized by exposing the inner layer of the subserosal layer

During laparoscopic cholecystectomy (LC), misidentification of the cystic duct, which causes major bile duct injuries, can result from wrong or incomplete dissection of Calot’s triangle. Therefore, the critical view of safety has been accepted as a safe method for gaining a sufficient view of Calot’s triangle before transecting the cystic duct. However, even in cases without aberrant anatomy of the bile duct, bile duct injury can occur by a wrong approach to a critical view of safety. Additionally, in cases of badly inflamed gallbladders, it is often hard to achieve a critical view of safety, because Calot’s triangle is often solid and cannot be expanded. In our standardized procedure, which is based on exposing the inner layer of the subserosal layer (the ss-i layer), the critical view of safety can be safely achieved. We have safely performed LC, using our standardized procedure, for many cases with cholecystitis with highly inflamed gallbladders. In this article, focusing especially on prevention of bile duct injuries, we present our standardized procedure to achieve the critical view of safety along with histological findings.     

Expression of HER2 and bradykinin B_1 receptors in precursor lesions of gallbladder carcinoma

AIM:To determine the expression of HER2 and bradykinin B 1 receptors(B 1 R) in the two pathogenic models of gallbladder cancer:the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma pathways.METHODS:Receptor proteins were visualized by immunohistochemistry on 5-μm sections of paraffin-embedded tissue.Expression of both receptors was studied in biopsy samples from 92 patients(6 males and 86 females;age ranging from 28 to 86 years,mean 56 years).High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridiza-tion.Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker.RESULTS:HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium.On the contrary,there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia(22/24;91.7%) and carcinoma in situ(9/10;90%),the lesions that displayed a significantly high proliferation index.Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification.A similar result was observed in invasive carcinomas(0/12).The B 1 R distribution pattern mirrored that of HER2 except that B 1 R was additionally observed in the adenomas.The B 1 R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia(24/24;100%) and carcinoma in situ(10/10;100%) and in the epithelial cells of adenomas.In contrast,both HER2(4/12;33%) and B 1 R(1/12;8.3%) showed a low expression in invasive gallbladder carcinomas.CONCLUSION:The up-regulation of HER2 and B1R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.