A case of advanced esophageal cancer with large liver metastasis successfully treated with FAP therapy

A 70-year-old man with dysphagia was diagnosed as advanced esophageal cancer by a primary doctor, and he was admitted to our hospital for treatment in February, 2004. The pretreatment diagnosis was basaloid squamous carcinoma, Mt area, T4 (aorta) , N2 (No. 107) , M1 (liver), Stage IVb performed systemic chemotherapy by FAP (5-fluorouracil ( 5-FU)+doxorubicin (DXR)+cisplatin (CDDP) ) from March, 2004. After 4 courses, the local tumor almost entirely disappeared, and the liver metastasis was obviously reduced. We continued chemotherapy afterwards. As of March 31, 2007, he had local lesion CR and metastatic lesion PR. It is very important to perform FAP repeatedly, for local and metastatic lesion of esophageal cancer while maintaining the patient's general condition and avoiding adverse events.     

Intraoperative Nomograms,Based on One-Step Nucleic Acid Amplification,for Prediction of Non-sentinel Node Metastasis and Four or More Axillary Node Metastases in Breast Cancer Patients with Sentinel Node Metastasis

Background

One-step nucleic acid amplification (OSNA) for cytokeratin 19 messenger RNA is an intraoperative diagnostic procedure for the detection of lymph node metastasis.

Objective

This study aimed to construct intraoperative nomograms using OSNA for the prediction of non-sentinel lymph node (NSLN) metastasis and four or more axillary lymph node (ALN) metastases.

Methods

Of the 4736 breast cancer patients (T1-3, N0) who underwent sentinel lymph node (SLN) biopsy and had SLNs examined intraoperatively with OSNA, 623 with SLN metastasis treated with completion ALN dissection (cALND) were retrospectively analyzed, and were randomly divided into training (n?=?312) and validation (n?=?311) sets.

Results

Of the clinicopathological parameters available preoperatively and intraoperatively, the multivariate analysis of the training set revealed that clinical tumor size and total tumor load (TTL) determined by OSNA were significantly associated with NSLN metastasis, and that clinical tumor size, number of macrometastatic SLNs, and TTL were significantly associated with four or more ALN metastases. Nomograms for NSLN metastasis and four or more ALN metastases were constructed using these parameters, and their area under the receiver operating characteristic curve (AUC) of the validation set were both 0.70, with a diagnostic accuracy similar to that of previously reported postoperative nomograms.

Conclusions

We constructed intraoperative nomograms using OSNA for the prediction of NSLN metastasis and four or more ALN metastases. These nomograms are as accurate as the conventional postoperative nomograms and might be helpful for decision making regarding the indication for cALND or the choice of adjuvant chemotherapeutic regimens and radiation field.

     

早期黏膜下胃癌微转移和微浸润的临床意义

目的 探讨临床早期黏膜下胃癌的淋巴结微转移和原发灶微浸润的临床意义。方法 对79例早期黏膜下胃癌患者手术切除的1945个淋巴结及68例肿瘤原发灶分别进行连续超薄切片,并应用抗细胞角蛋白(CK)单克隆抗体(CAM5．2)进行免疫组化检测并结合临床病理学指标及患者预后进行综合分析研究。结果 常规HE染色时,淋巴结转移率为13％(10／79),而CK染色为34％(27／79)。早期黏膜下胃癌的微转移发生率为25％(17／69)。68例早期黏膜下胃癌患者中,微浸润的发生率为16％(11,／68)。淋巴结微转移分别多发于肿瘤直径大于2cm(43％),凹陷型(48％),淋巴管侵犯(73％)和深度黏膜下侵犯(53％)的肿瘤。微浸润多发于低分化癌(33％)和深度黏膜下侵犯(31％)的肿瘤。5年生存率在没有微转移的患者为100％,有微转移的患者为82％,有微浸润的患者为73％。结论 CK免疫组化检查在诊断微转移和微浸润上明显优于常规HE检查。淋巴结的微转移和原发灶的微浸润明显影响黏膜下胃癌患者预后。     

Overexpression of MT3-MMP in hepatocellular carcinoma correlates with capsular invasion

BACKGROUND/AIMS: Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably up-regulated in epithelial cancers and are key agonists of angiogenesis, invasion and metastasis. Recent studies have shown high levels of various MMPs, including MT1-MMP, MMP-1, MMP-2 and MMP-9, and their involvement in tumor progression in human hepatocellular carcinoma (HCC). However, the expression and role of MT3-MMP in HCC remains unclear. METHODOLOGY: We examined the immunohistochemical expression of MT3-MMP in surgically resected HCCs (n=58), hepatitis C virus (HCV) and hepatitis B virus (HBV)-related chronic hepatitis (n=34) and cirrhosis (n=24). RESULTS: MT3-MMP expression was observed in all non-cancerous liver tissues. In HCCs, 52% (30/58) of patients showed high MT3-MMP expression while the remaining 48% (28/58) of patients showed low expression. A clinicopathological survey demonstrated a significant correlation between high MT3-MMP expression and capsular invasion of carcinoma (p = 0.034) although there was no correlation between high MT3-MMP expression in HCC and overall survival or disease-free survival. CONCLUSIONS: MT3-MMP was expressed not only in chronic hepatitis and liver cirrhosis, but also in HCC, and high MT3-MMP expression correlated significantly with capsular invasion of carcinoma.     

Anatomical variations and surgical strategies in right lobe living donor liver transplantation: lessons from 120 cases

BACKGROUND: Anatomical variations in right liver lobe are common. However, clinical implications and surgical management of these variations in living donor liver transplantation have not been analyzed systematically. METHODS: Surgical anatomy of vascular and biliary structures in 120 right lobe grafts were reevaluated by reviewing the results of preoperative (computerized tomography and Doppler ultrasonography) and intraoperative (cholangiography) imaging as well as surgical findings. The data were analyzed in relation to surgical management of anatomical variations. RESULTS: The incidence of variants leading to multiple portal vein anastomoses was 7.5%. The incidence of dual right hepatic veins was 0.8%; 30% of the grafts had significant accessory hepatic veins (>5 mm) and 13.9% of these were multiple. All of them were successfully reconstructed with technical modifications including venoplasty and venous grafts, except for two cases with multiple intraparenchymal portal vein branches to the anterior segment. The incidence of dual hepatic arteries was 1.7%, but only one of them was reconstructed without negative sequelae. The incidence of variants potentially leading to multiple bile duct anastomoses was 35.0%, and eventually 39.2% of the grafts had multiple orifices. With a variety of techniques including ductoplasty, hepaticohepaticostomy, and biliary stent, total incidence of leakage and stenosis was 10.8% and 9.2%, respectively. Although ductoplasty, internal stent or no stenting, seemed to be associated with increased risk of complications, anatomical variants, multiple bile ducts, and duct-to-duct reconstruction did not bear a significant risk. CONCLUSIONS: Anatomical variations of vascular and biliary structures in right lobe grafts are common. However, most can be managed safely with technical modifications. Only cases with intraparenchymal origin of the anterior portal vein(s) may form a relative contraindication, especially when combined with similar biliary variants. Otherwise, intraoperative assessment of biliary anatomy was enough for successful management. Detailed and precise assessment of vascular and biliary anatomy is vital for appropriate surgical management.     

Low dose citalopram reverses memory impairment and electroconvulsive shock-induced immobilization

Citalopram, a selective serotonin reuptake inhibitor (SSRI), is one of the most widely used antidepressants. Recently, citalopram has been reported to improve working memory in patients with depression, and psychotic symptoms and behavioral disturbances in patients with dementia. However, the possibility of using citalopram in the treatment of cognitive disorders has not received much attention. The present study investigated the effects of citalopram on scopolamine- and Delta9-tetrahydrocannabinol (THC)-induced impairment of spatial memory using an eight-arm radial maze and electroconvulsive shock (ECS)-induced immobilization (a behavioral model for the disturbance of consciousness). Low dose citalopram reversed both scopolamine- and THC-induced impairment of spatial memory, suppressed ECS-induced immobilization reversed the THC-induced decrease of acetylcholine (ACh) release in the dorsal hippocampus in vivo microdialysis, and enhanced tremors induced by oxotremorine, a muscarinic M1 receptor agonist. Taken together these findings suggest that low dose citalopram is useful for the treatment of memory deficits and consciousness disturbance.     

Promoter hypermethylation of E-cadherin and its abnormal expression in Epstein-Barr virus-associated gastric carcinoma

Promoter hypermethylation of various tumor-related genes is extremely frequent in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC). To investigate the significance of the promoter methylation in EBVaGC, we focused on one of the important proteins in the carcinogenesis of the stomach, E-cadherin. Methylation-specific PCR analysis (MSP) was applied to surgically resected gastric carcinomas, together with immunohistochemistry, PCR-based analysis of mutations and allelic loss, and site-specific MSP of E-cadherin gene. By MSP, nearly all of the carcinomas showed aberrant methylation of E-cadherin promoter in EBVaGC (21/22), and the frequency of this aberration was significantly higher than that in EBV-negative gastric carcinoma (GC; 45/81; p = 0.0003). According to immunohistochemistry of E-cadherin, the frequency of abnormal staining pattern in EBVaGC (87%) was comparable to that in the diffuse type (80%), but higher than that in the intestinal type of EBV-negative GC (47%). Promoter methylation was well correlated with abnormal staining pattern in EBVaGC, but not in EBV-negative GC. Neither mutation nor allelic loss of E-cadherin was observed in EBVaGC. Methylation status of E-cadherin within each carcinoma was heterogeneous as far as examined. Thus, in addition to the known association involving p16, we determined that promoter methylation-mediated silencing of E-cadherin gene was also closely associated with the development of EBVaGC, although it becomes heterogeneous within a given tumor along its progression.     

Thymidine phosphorylase expression as a prognostic marker for predicting recurrence in primary superficial bladder cancer

No prognostic marker for predicting recurrence in primary superficial bladder cancer has been established. The aim of this study was to investigate the expression levels of thymidine phosphorylase (TP) by enzyme-linked immunosorbent assay (ELISA) and the immunohistological localization of TP in primary superficial bladder cancer tissue to assess its association with tumor recurrence and stage progression as well as the pathological parameters of the tumor. TP expression in cancer tissues from 77 patients was measured by sandwich-type ELISA. Clinicopathological factors and the clinical prognosis were examined in relation to the expression levels of TP. To clarify the clinicopathological implication of TP localization in primary superficial bladder cancer tissue, the immunohistochemically determined TP expression was assessed for histological grades 1-3. The TP expression in primary superficial bladder cancer significantly increased with the histological grade and stage. The TP expression in patients with a shift to invasive cancer was significantly higher than in those without invasive cancer. Patients with low TP expression had a significant longer postoperative tumor-free period than those with high TP expression (P=0.011). High TP expression was an independent prognostic factor for tumor recurrence (P=0.0441). Strong immunoreactivity for TP was observed in the cytoplasms of tumor cells and vascular endothelial cells. This study suggests that elevated TP expression may be a prognostic marker for predicting recurrence in primary superficial bladder cancer, and that high TP expression may be associated with the marked proliferation of tumor cells and increased vascular endothelial cells, showing strong immunoreactivity for TP.