Laparoscopic repair of a primary parahiatal hernia combined with gastric volvulus: a case report and literature review.

BACKGROUND: Parahiatal hernias present a hernial orifice at the diaphragm that is adjacent to the esophageal hiatus, differing from the paraesophageal type of hiatal hernias. Although diagnostic imaging has advanced in recent years, diagnosing parahiatal hernias remains challenging. We herein report a case in which we performed laparoscopic surgery and intraoperatively diagnosed a parahiatal hernia. CASE PRESENTATION: A 67-year-old man presented to our hospital with difficulty eating, epigastric pain, and vomiting. We suspected a paraesophageal hiatal hernia. Laparoscopic surgery was performed, and a diagnosis of parahiatal hernia was made. We closed the hernial orifice with direct simple closure using nonabsorbable threads. The patient's postoperative recovery course was reasonable, and he was discharged on the twelfth postoperative day. CONCLUSIONS: Parahiatal hernias are rare, and a definitive diagnosis is difficult. Laparoscopic surgery can help accurately diagnose and treat patients presenting with the condition.

Membranous nephropathy associated with type 1 autoimmune pancreatitis and dominant glomerular IgG4 deposit.

We report a case of membranous nephropathy associated with type 1 autoimmune pancreatitis. A 58-year-old man presented with anorexia. Work-up revealed a mass in the pancreatic head, which was subsequently resected. Pathological examination showed diffuse infiltration of immunoglobulin (Ig) G4-positive plasma cells, which was compatible with the diagnosis of type 1 autoimmune pancreatitis. Serum IgG4 was elevated. He developed nephrotic syndrome around the time of the surgery. Kidney biopsy confirmed the diagnosis of membranous nephropathy. Immunofluorescent staining showed predominant glomerular IgG4 deposit among IgG subclasses. Tubulointerstitial nephritis, which is usually a dominant feature of renal involvement in IgG4-related disease, was not observed. The patient was treated with prednisolone and several immunosuppressants. During the course, the degree of proteinuria was associated with the serum IgG4 level. Serum antibody against phospholipase A2 receptor was negative. These findings together with IgG4-dominant glomerular deposit suggest that IgG4 may play a unique role in the pathogenesis of secondary membranous nephropathy caused by IgG4-related diseases.

Selective accumulation of platinum and formation of platinum-DNA adducts in hepatocellular carcinoma after transarterial chemoembolization with miriplatin.

AIM: Miriplatin, a lipophilic platinum complex, is a novel intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). Little is known about platinum-DNA adduct levels in human HCC after administration of platinum-based drugs. We investigated whether miriplatin selectively accumulates and forms platinum-DNA adducts in human HCC tumors. METHODS: Using inductively coupled plasma mass spectrometry, we determined the platinum concentrations and platinum-DNA adduct levels in paired HCC tumors and non-tumor liver tissues of four patients who received transcatheter arterial chemoembolization with miriplatin and subsequently underwent hepatic resection. RESULTS: The mean (± standard deviation) platinum concentrations were 730 ± 350 µg/g (range, 400-1100) in HCC tumors and 16 ± 9.2 µg/g (range, 9.2-29) in non-tumor liver tissues. The concentrations were approximately 50-fold higher in HCC tumors than in non-tumor liver tissues. The mean platinum-DNA adduct levels were 54 ± 16 pg Pt/µg DNA (range, 37-69) in HCC tumors and 13 ± 13 pg Pt/µg DNA (range, 4.8-33) in non-tumor liver tissues. The adduct levels were roughly 7.6-fold higher in HCC tumors than in non-tumor liver tissues. There were no significant correlations between platinum concentrations and platinum-DNA adduct levels in HCC tumors. CONCLUSION: Our results quantitatively demonstrate that there is a selective accumulation of platinum and formation of platinum-DNA adducts in human HCC tumors after transarterial chemoembolization with miriplatin. No correlation was observed between platinum concentrations and platinum-DNA adduct levels.

Hemorrhage from varices in hepaticojejunostomy in the fifth and tenth year after surgery for hepatic hilar bile duct cancer: a case report.

We report a case of a 64-year-old female patient who underwent a right lobectomy of the liver (including total resection of the caudate lobe), dissection of the group 2 lymph nodes, left hepaticojejunostomy (Roux-en-Y fashion), and reconstruction of the portal vein (end-to-end anastomosis between the main portal vein and the left portal branch) for treatment of hepatic hilar bile duct cancer in 1996. In 2001, the anastomotic site of the hepaticojejunostomy was dissected and re-anastomosed due to gastrointestinal bleeding caused by variceal rupture in the jejunal loop. In 2006, splenectomy was performed for recurrence of gastrointestinal bleeding due to another variceal rupture in the jejunal loop. Portal venography performed perioperatively showed a decrease in portal blood flow into the liver via the jejunal varices and an increase in portal blood flow into the liver via the left gastric vein. She had two jejunal variceal ruptures at five-year intervals after extrahepatic portal obstruction and underwent successful treatments.

Possible inhibition of cancer cell adhesion to the extracellular matrix in NK4-induced suppression of peritoneal implantation.

Milky spots (MS), peritoneal lymphoid tissues, expose the extracellular matrix (ECM) due to a defect of mesothelial cells on their surface, which may explain why peritoneal implantation of cancer cells preferentially takes place at MS. We recently reported that adenovirus vector-mediated intraperitoneal production of NK4 strongly suppressed MS-selective implantation of cancer cells and subsequent peritoneal dissemination, without histological evidence of angiogenesis inhibition. The present study was conducted to clarify the mechanisms underlying the suppressive effects of NK4 on peritoneal implantation. In mice intraperitoneally injected with CT26 cells that were genetically modified to produce NK4 (CT26-NK4), peritoneal dissemination was significantly suppressed with survival prolongation. A decreased cell implantation to omental MS was also detected and evaluated by green fluorescence protein (GFP) imaging. In an in vitro adhesion assay, hepatocyte growth factor-stimulated adhesion to ECM components, such as fibronectin and collagen, was inhibited in CT26-NK4 compared to control cells. These results strongly suggest an inhibition of cancer cell adhesion to the ECM in the suppression of peritoneal implantation by NK4.

Suppression of peritoneal implantation of gastric cancer cells by adenovirus vector-mediated NK4 expression.

Peritoneal dissemination is the most common mode of metastasis in gastric cancer. We previously reported the importance of milky spots (MS), peritoneal lymphoid tissues, as selective sites of cancer implantation in peritoneal dissemination. In the present study, we first demonstrated that intraperitoneal injection of adenovirus vector encoding the GFP gene into tumor-free nude mice resulted in GFP expression at omental and mesenteric MS; MS macrophages were target cells for adenovirus infection. We confirmed that intraperitoneal injection of adenovirus vector encoding the NK4 gene (AdNK4) resulted in NK4 production localized to the peritoneal cavity, especially the omentum. Adenovirus vector-mediated MS-selective transgene expression was markedly impaired in tumor-bearing mice whose MS had already been replaced by infiltrating cancer cells. However, prior injection of AdNK4 successfully inhibited MS-selective cancer cell implantation, resulting in suppression of peritoneal dissemination and prolongation of survival. Adenovirus vector-mediated MS-selective delivery of a therapeutic gene may prevent peritoneal dissemination of gastric cancer.

Reduced HGF expression in subcutaneous CT26 tumor genetically modified to secrete NK4 and its possible relation with antitumor effects.

Tumor-stromal interactions, which are regulated by stromal-derived HGF and tumor-derived HGF inducers, are essential for tumor cell acquisition of such malignant properties as invasion and metastasis. NK4, a proteolytic cleavage product of HGF, has antitumor activities as both an HGF antagonist and an angiogenesis inhibitor. In this study, we examined the in vitro and in vivo behaviors of mouse colon adenocarcinoma C T26 cells modified by gene transfer to secrete NK4, and investigated the influence of NK4 on expression of HGF and HGF inducers associated with tumor-stromal interactions. In vitro cell proliferation rates of NK4 transfectant (C T26-NK4) and mock transfectant (C T26-NEO) were essentially the same, and scattering and invasion were stimulated by HGF in C T26-NEO, but not in C T26-NK4. In syngeneic BALB/c female mice, subcutaneous tumor growth of C T26-NK4 was potently suppressed, and the survival was prolonged significantly. Immunohistochemistry showed significantly decreased microvessels and increased apoptotic cells in C T26-NK4 tumor compared with control. Interestingly, HGF, strongly expressed in C T26-NEO tumor stroma, was reduced in C T26-NK4. In vitro, conditioned medium of C T26-NK4 inhibited fibroblast-derived HGF production, which was increased by that of C T26-NEO. Moreover, although similar constitutive expression levels of PDGF and TGF-alpha (both HGF inducers) were detected in C T26-NK4 and C T26-NEO in semiquantitative RT-PCR analyses, the expression was up-regulated by HGF in C T26-NEO, but not C T26-NK4. These results suggest that NK4 may exert antitumor activities not only by antagonizing HGF, but also by inhibiting HGF amplification via tumor-stromal interactions. Continuous, abundant NK4 production induced at a tumor site by gene transfer should show multiple antitumor activities with potential therapeutic benefit.

[Growth suppression of subcutaneous tumor by CT26 expressing NK4 in syngeneic mice].

An HGF antagonist, NK4, inhibits not only invasion and metastasis of tumor cells driven by HGF-Met receptor binding, but also tumor angiogenesis. To address the antitumor activities of NK4, we investigated the biological behaviors of CT26 transfected with the NK4 gene (CT26-NK4) in vitro and in vivo. In the in vitro assay, the invasion in MOCK transfected cells (control) was stimulated by HGF; however, in CT26-NK4 cells, these effects were completely inhibited. In the in vivo assay, the tumor growth of CT26-NK4 was strongly suppressed and the survival of CT26-NK4 tumor-bearing mice was significantly prolonged. Immunohistochemical analysis revealed that while proliferating cells (PCNA immunostaining) of CT26-NK4 tumors were weakly suppressed, the micro-vessel number (CD31/PECAM-1 immunostaining) in those tumors was significantly suppressed as compared with the control tumors. In conclusion, NK4 exerts potent antitumor effects via anti-angiogenesis rather than inhibition of biological events of tumor cells stimulated by HGF.

[Functional analysis of peritoneal lymphoid tissues by GFP expression in mice--possible application for targeting gene therapy against peritoneal dissemination].

It is important to develop an efficient adjuvant therapy for the prevention of the postoperative peritoneal recurrence of gastrointestinal cancers such as gastric cancer or pancreatic cancer. Milky sports (MS) are peritoneal lymphoid tissues broadly distributed on the peritoneal tissues such as the omentum, mesentery, or Douglas pouch, and are the selective implantation sites of disseminated cancer cells. In this study, we introduced GFP gene into various cancer cell lines and host-derived cells such as peritoneal macrophages and dendritic cells by adenovirus vetor and injected them i.p. into mice. We then investigated the sites of GFP expression on the peritoneum by fluorescence microscopy. The results showed that green fluorescence was detected specifically for the MS sites that stained black with activated carbon particles (CH40), despite the differences in the cell type injected. These findings indicate that 1) the physioanatomical characteristics of MS may play an essential role in the formation of the initial disseminated lesions at MS, and 2) the host-derived cells accumulating near MS may be available as carriers of a therapeutic gene in intraperitoneal gene therapy against peritoneal dissemination.