[A case of inflammatory myofibroblastic tumor with rapidly progressive growth arising from the retroperitoneum].

A woman in her 70s was admitted to our institution with complaints of right hypochondrium pain. Abdominal computed tomography revealed a 13-mm retroperitoneal tumor between the liver and right kidney. The tumor rapidly increased to 82mm within 2 months, a necrotic change was inside the tumor, and the inflammation spread to the surrounding diaphragm and the peritoneum. The patient underwent surgical resection including the affected diaphragm and the peritoneum. Histopathological examination revealed a myofibroblastic spindle-cell proliferation with prominent infiltration of inflammatory cells, such as the plasma cells, lymphocytes, neutrophils, and eosinophils, diagnosed as an inflammatory myofibroblastic tumor (IMT) based on positive smooth muscle actin staining. IMT arising from the retroperitoneum is a rare case in Japan;we report this case with literature review.

[Curatively Resected Stage â £Gastric Cancer with Positive Peritoneal Cytology Due to SOX Therapy-A Case Report].

A 70-year-old man with epigastralgia who initially visited a local hospital was referred to us for further examination. Gastrointestinal endoscopy exhibited a type 3 tumor of the stomach from the body to the antrum(adenocarcinoma, por1). Contrast-enhanced CT revealed thickness in the wall of the gastric body with bulky lymph nodes and ascites. Staging laparoscopy showed that the patient was diagnosed with sStage Ⅳ gastric cancer with positive peritoneal cytology. Therefore, SOX therapy was administered. Subsequently, total gastrectomy with D2 lymph node dissection was performed, since the primary tumor and lymph nodes were significantly reduced. Histopathologically, the residual lesion was only observed in the mucosal layer without lymph node metastases. We herein report a case of Stage Ⅳ gastric cancer, which was successfully treated by conversion surgery after SOX therapy.

Glasgow prognostic score predicts outcome after surgical resection of gallbladder cancer.

BACKGROUND: Systemic inflammation as evidenced by the Glasgow prognostic score (GPS) predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS in therapeutic outcome after surgical resection of gallbladder cancer. METHODS: The subjects were 51 patients who underwent surgical resection for gallbladder cancer. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥3.5 g/dl) and normal C-reactive protein (CRP) (≤1.0 mg/dl) as GPS 0 (n = 38), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n = 8), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n = 5). We retrospectively investigated the relation between patient characteristics including GPS, and disease-free as well as overall survival. RESULTS: In disease-free survival, advanced tumor stage based on pathology (p = 0.006), positive lymph node metastasis (p = 0.001), and GPS 1 or 2 (p = 0.006) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, positive lymph node metastasis (p = 0.002) and GPS 1 or 2 (p = 0.032) were independent predictors of poor patient outcome in multivariate analyses. CONCLUSION: The GPS in patients with gallbladder cancer is an independent prognostic predictor after surgical resection.

[A case of eosinophilic gastroenteritis with perforative peritonitis].

A 44-year-old man was admitted to our hospital with abdominal pain. Enhanced abdominal computed tomography demonstrated intraperitoneal free air and fluid collection. Peritonitis due to intestinal perforation was suspected and an emergency laparotomy was performed. Exploration of the abdominal cavity confirmed perforation of the ileum at a site 20cm from the terminal ileum. Therefore, we performed partial ileal resection that included the perforation and placed an ileostomy. Histopathological examination of the ileum revealed infiltration of eosinophilic leukocytes between the submucosal and subserosal layers, compatible with the diagnosis of eosinophilic gastroenteritis.

Nuclear factor κB activity correlates with the progression and prognosis of pancreatic cancer in a mouse model.

INTRODUCTION: Constitutive NF-κB activation is considered to play a key role in the aggressive behavior of pancreatic cancer. Although NF-κB in tumors may contribute to aggressive characteristic features via transcription of angiogenesis and invasion-related factors, there is no definitive evidence showing a correlation between quantitated NF-κB activity and prognosis. In this study, we quantitated NF-κB activity of various human pancreatic cancer cell lines and evaluated whether NF-κB activity was related to tumor progression and prognosis for pancreatic cancer in mice. MATERIALS AND METHODS: We quantitated NF-κB activity in six pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, MIAPaCa-2, Panc-1 and PL45) and evaluated downstream target genes of NF-κB such as VEGF, IL-8 and MMP-9 in vitro. Next, we evaluated tumor progression and prognosis using subcutaneous tumor model in vivo between cell lines with the highest and lowest NF-κB activity. RESULTS: BxPC-3 had the highest and AsPC-1 had the lowest NF-κB activity in the 6 cell lines. Expression of VEGF, IL-8 and MMP-9 in BxPC-3 was significantly higher than those in AsPC-1 cells in vitro (p < 0.001) and tumor growth in BxPC-3 was faster than that in AsPC-1 group (p < 0.001) resulting in worse survival in vivo (p = 0.0339). CONCLUSION: These results suggested that NF-κB activity is related to expression of its downstream target genes, tumor progression and prognosis in experimental pancreatic cancer model.

Strategies to Perform Curative Laparoscopic Repeat Hepatectomy for Recurrent Liver Tumors After Open Right Lobectomy.

BACKGROUND: Although indications of laparoscopic hepatectomy have been expanded, the laparoscopic approach after right hepatic lobectomy has a very high burden. The purpose of this study was to evaluate patients undergoing laparoscopic repeat hepatectomy for recurrent hepatic tumors after open right lobectomy. PATIENTS AND METHODS: Five cases of laparoscopic repeat hepatectomy for recurrent hepatic tumors after open right lobectomy were included in the study. RESULTS: All the tumors in segment 3 were intraoperatively detected and curatively resected by partial hepatectomy. The tumors in segment 2 could not be detected intraoperatively due to hypertrophic liver deformity and adhesion. They were curatively resected by anatomical subsegmental approach. CONCLUSION: For recurrent tumors located in segment 2 after right lobectomy, anatomical subsegmental approach should be preferred, not only from an oncological standpoint, but also for securing curative laparoscopic resection and overcoming anatomical difficulties.

Minimizing intraoperative bleeding using a vessel-sealing system and splenic hilum hanging maneuver in laparoscopic splenectomy.

BACKGROUND/PURPOSE: The most common cause of conversion to laparotomy (open splenectomy) during laparoscopic splenectomy (LS) is bleeding from the splenic hilar vessels. Recently, the efficacy of Ligasure (a vessel-sealing system) as a safety device for sealing vessels and reducing intraoperative blood loss has been reported with various laparoscopic procedures. The objective of this report was to describe our techniques for minimizing bleeding during LS, characterized by the application of Ligasure (which reduces the number of clips and staples, and reduces unnecessary bleeding) and a splenic hilum hanging maneuver with a Diamond-Flex flexible retractor to obtain optimal exposure of the splenic hilum. METHODS: We have performed 87 LSs since February 1993, and have employed the Ligasure instead of metal clips and staplers since September 2003. We have also introduced the splenic hilum hanging maneuver paired with Ligasure use. We have performed this new LS in 30 consecutive adult patients presenting with idiopathic thrombocytopenic purpura (n = 14), benign splenic tumor (n = 5), lymphoma (n = 4), hereditary spherocytosis (n = 2), liver cirrhosis (n = 2), and other pathologies (n = 3). The splenic ligaments and vessels, including the splenic artery and vein, were divided using a 5-mm Ligasure instead of a clip or stapler. The splenic hilum was encircled and elevated, using a Diamond-Flex, to ensure better exposure in all patients. RESULTS: LS was successfully completed in 29 patients (97%), with only one conversion to open splenectomy. Mean blood loss for all patients with completed LS was only 21.6 ml (range 0-250 ml). Moreover, blood loss was not determinable (considered as 0 ml in this study) in 15 patients (52%). Mean spleen weight and operating time were 319.4 g (range 80-1605 g) and 143.4 min (range 90-180 min), respectively. No postoperative mortalities were encountered. Two patients experienced complications, including grade B pancreatic fistula and atelectasis, for an overall morbidity rate of 6.7%. Mean postoperative stay was 6.5 days (range 3-14 days). CONCLUSIONS: LS using a Ligasure in combination with the splenic hilum hanging maneuver may reduce intraoperative blood loss.

Adenovirus-mediated CD40L gene therapy induced both humoral and cellular immunity against rat model of hepatocellular carcinoma.

Adenoviral-vector expressing CD40L (AxCAmCD40L)-mediated gene therapy was studied for treatment of hepatocellular carcinoma (HCC) using CD40 ligand (CD40L) complementary DNA in rats. The particular focus was whether humoral immunity took part in antitumor effect. When tumor cells transduced by AxCAmCD40L were implanted into the subcutaneous tissues of syngeneic rats, the tumor growth was suppressed. Intratumoral injection of AxCAmCD40L to pre-existing tumor in rats also led to significant reduction of tumor size. When tumor cells were re-implanted to prevention model rats and treatment model rats, no tumor growth was observed. Many studies to date have reported that cellular immunity induces antitumor immunity. However, the present study demonstrated that not only cellular immunity but also humoral immunity plays an essential role in a HCC model. These observations suggested that CD40L-mediated immune gene therapy for HCC was very effective treatment by activation of both cellular and humoral immune system.

Immunogene therapy by adenovirus vector expressing CD40 ligand for metastatic liver cancer in rats.

BACKGROUND: We have explored a gene-therapeutic approach to stimulate antitumor immunity by adenoviral-mediated transfer of CD40 ligand (CD40L) to treat metastatic liver cancer in a rat model. MATERIALS AND METHODS: Rat metastatic liver cancer cells were implanted into the back of rats bilaterally. When the larger tumor reached 8.0 mm in diameter, adenovirus vector-expressing mouse CD40L was injected intratumorally as treatment group (n=5), while LacZ was injected in the control group (n=5). RESULTS: In the control group, the tumor gradually grew to be 20.7+/-1.6 (mean+/-SD) mm in intratumorally injected tumors and 21.8+/-3.7 mm in opposite tumors seven weeks after injection, respectively. In contrast, in the treatment group, the tumor was reduced to 3.6+/-8.2 mm and 3.7+/-8.2 mm. The tumor growth and survival rate were significantly different (p<0.001). CONCLUSION: Adenovirus vector-mediated CD40L gene therapy is an effective therapeutic method for metastatic liver cancer.

A novel approach for gene transduction with adenovirus vector and the fibrin glue system.

BACKGROUND: The fibrin glue system (FGS) consists of liquid forms of fibrinogen and thrombin and is used widely in surgery for hemostasis. In this study, as a novel and unique approach, the possibility and efficacy of locoregional gene transfer using the FGS containing an adenoviral vector was determined. MATERIALS AND METHODS: The optimum concentration of the adenoviral vector mixed with the FGS (AxCALacZ/FGS) for gene transduction was evaluated in vitro by X-gal (beta-galactosidase) staining and NIH (National Institute of Health) imaging in RCN-9, a rat colon carcinoma cell line. To determine the survival period of the adenoviral vector in the fibrin glue, RCN-9 cells were exposed to AxCALacZ/FGS after it had been incubated for various periods and the transduction efficiencies were evaluated by beta-galactosidase (beta-gal) assay. AxCALacZ/FGS was also applied in vivo to the resected site of rat liver. AxCALacZ diluted in PBS (AxCALacZ/PBS) was used as the control. The transduction efficiencies in the liver were compared by X-gal staining and beta-gal assay. RESULTS: Almost 100% transgene expression was demonstrated by the X-gal staining and NIH imaging at a concentration level greater than 1 multiplicity of infection. LacZ expression (as beta-galactosidase) revealed gene-transduced RCN-9 cells when the AxCALacZ/FGS was held for a period of less than 96 hours. The treatment with the AxCALacZ/FGS in vivo resulted in greater transgene expression than the treatment with AxCALacZ/PBS. CONCLUSION: The adenoviral vector survives and remains stable in the FGS for sufficient time for transduction to occur and AxCALacZ/FGS can efficiently transduce the target gene both in vitro and vivo.

Adenovirus vector-mediated gene therapy using iodized oil esters for hepatocellular carcinoma in rats.

BACKGROUND: When gene therapy is performed for malignant tumors, gene transfer efficiency and selectivity are extremely important. The usefulness of gene therapy by intraarterial injection of an adenovirus vector with iodized oil esters (IOEs) for hepatocellular carcinoma (HCC) was studied. MATERIALS AND METHODS: HCC was induced in rats with diethyl nitrosamine and phenobarbital, after which either adenovirus vector expressing the herpes simplex virus thymidine kinase (AxCAHSVtk) and IOEs or AxCAHSVtk alone was injected through the hepatic artery. On postoperative days 2, 4 and 6, gancyclovir was injected into the peritoneum; blood sampling was performed on day 7. RESULTS: Aspartate aminotransferase and alanine aminotransferase levels in the AxCAHSVtk with IOEs group were lower than in the AxCAHSVtk alone group (p = 0.0274, p = 0.0323). However, the survival rate was not significantly different between groups (p = 0.7122). CONCLUSION: Intra-arterial injection of an adenovirus vector with IOEs can result in cancer-selective but not effective gene therapy for HCC.

Geriatric nutritional risk index predicts surgical site infection after pancreaticoduodenectomy.

Surgical site infections (SSIs) are a well-known potential complication of surgery. They are assocaited with preoperative malnutrition and lead to increased medical costs and longer hospital stays. Therefore, surgeons should appropriately identify patients who are at a high risk. The geriatric nutritional risk index (GNRI) is a tool, increasingly utilized to assess the degree of malnutrition, particularly in elderly patients. Therefore, the present study attempted to validate whether GNRI could predict the risk of SSI in patients following pancreaticoduodenectomy (PD). A cohort study was retrospectively conducted on 106 patients in the Department of Digestive Surgery, Kawaguchi Municipal Medical Center, Japan from January 2007 to December 2017. All patients were subjected to nutritional screening using GNRI and followed up for the occurrence of postoperative complications, including SSI post PD. Additionally, risk factors for developing SSI, and the patient's height, body mass index and preoperative laboratory values were documented. Patients were divided into SSI (n=15) and non-SSI (n=91) groups with a determined incidence of 14.2% (15/106) for SSI. The results revealed that the SSI group had GNRI values that were significantly reduced compared with the non-SSI group (P<0.001). Receiver operating characteristic curve analysis was performed to determine the cut-off value of GNRI that conferred an increased risk of SSI; it was determined as 94 (sensitivity 80.0%, specificity 83.5%). Univariate analysis confirmed that a GNRI <94 was significantly associated with SSI (P<0.001), whereas multivariate logistic regression analysis revealed that a GNRI <94 was independently associated with SSI following PD (relative risk=1.73, 95% confidence interval=1.23-2.43; P<0.001). Therefore, a GNRI <94 is a potential predictive marker for SSI risk following PD.

Hepatic angiosarcoma mimicking hepatic epithelioid hemangioendothelioma: report of a case.

A 78-year-old male was admitted to our hospital for treatment of multiple hepatic tumors, which were suspected as hepatic epithelioid hemangioendothelioma (HEHE) by percutaneous tumor needle biopsy. With a diagnosis of HEHE, the patient underwent hepatic resection. In pathological findings, the tumor was composed of numerous endothelial cells without epithelioid cells, and was diagnosed as hepatic angiosarcoma (HAS). The patient received percutaneous radiofrequency ablation for recurrent HAS at 5 and 25 months postoperatively, and remains well with recurrence as of 28 months after the primary hepatic resection. In spite of improvement in radiological imaging, preoperative differential diagnosis between HAS and other malignant vascular tumors of the liver is still difficult. We herein report a case of HAS mimicking HEHE, treated successfully.

Complete response to post-transplant lymphoproliferative disorder by surgical resection and rituximab after living-donor liver re-transplantation for recurrent primary sclerosing cholangitis.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. We herein report a case of PTLD after living-donor liver re-transplantation (reLDLT) for recurrent primary sclerosing cholangitis (PSC), for which complete response was achieved by surgical resection and rituximab. A 47-year-old man, who had undergone living-donor liver transplantation (LDLT) twice at age of 43 and 45 years for end-stage liver disease firstly for PSC and secondary for recurrent PSC, suffered liver dysfunction due to an acute cellular rejection (ACR) 17 months after reLDLT. At reLDLT, a right liver lobe was donated from his spouse. Although steroid was effective for ACR, PTLD developed in the ileocecal area. The patient received rituximab for treatment of PTLD, and ileocecal resection for hemorrhage from ileocecal PTLD. The patient achieved complete response by rituximab and surgical resection for PTLD, but PSC recurred and hemophagocytic syndrome (HPS) developed with hyperbilirubinemia and elevated serum ferritin. The patient received steroid treatment for HPS, but thrombocytopenia and coagulopathy developed presumably due to thrombotic microangiopathy. Therefore, tacrolimus was switched to mycophenolate mofetil. Despite intensive treatment including plasmapheresis and platelet infusion, fungal infection of both lungs developed, and the patient died 22 months after reLDLT. Autopsy revealed complete response of PTLD, recurrence of PSC and persistance of HPS.

Glasgow prognostic score predicts therapeutic outcome after hepatic resection for hepatocellular carcinoma.

Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS), predicts cancer-specific survival in various cancer types. The aim of this study was to evaluate the significance of the GPS in the therapeutic outcome of the patient following surgical resection for hepatocellular carcinoma. In total, 144 patients underwent surgical resection for hepatocellular carcinoma. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10). Retrospectively, the relationship between patient characteristics including GPS, disease-free as well as overall survival were investigated. In disease-free survival, GPS 2 (P=0.019), with a tumor number ≥3 (P=0.004), and positive portal or venous invasion (P=0.034) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, GPS 1 (P=0.042), GPS 2 (P<0.001) and positive portal or venous invasion (P<0.001) were independent predictors of poor patient outcome according to multivariate analysis. To conclude, the GPS in patients with hepatocellular carcinoma is an independent prognostic predictor after hepatic resection.

NEMO peptide inhibits the growth of pancreatic ductal adenocarcinoma by blocking NF-κB activation.

NF-κB essential modulator (NEMO) binds and regulates IκB kinase (IKK) and is required for NF-κB activation. The NEMO-binding domain peptide (NBDP) of IKK was found to inhibit NF-κB activation and promote apoptosis in cancer cells. Studies have shown that constitutive NF-κB activation, one of the signature molecular alterations in pancreatic ductal adenocarcinoma (PDAC), is a potential therapeutic target. However, preclinical and therapeutic evidence that supports direct targeting of IKK activation in therapy is lacking. The aim of this study was to determine whether the combination of NBDP and gemcitabine would sensitize pancreatic cancer to the gemcitabine. We confirmed that NBDP inhibited NF-κB activation and found that NBDP indeed promoted chemo-sensitivity to gemcitabine in PDAC. NBDP increased PARP and caspase 3 cleavage in the apoptosis pathway, increased apoptosis of PDAC cells, and suppressed PDAC cell growth in vitro. In addition, NBDP combined with gemcitabine significantly decreased levels of NF-κB activity and inhibited the growth of PDAC in vivo in an orthotopic xenograft mouse model. Mechanistic investigations showed that NBDP effectively competed with NEMO/IKKγ for binding to IKKs and thus inhibited IKK and NF-κB activation, down-regulated expression levels of Erk, and decreased PDAC cell growth. Taken together, our current data demonstrate that NBDP sensitizes human pancreatic cancer to gemcitabine by inhibiting the NF-κB pathway. NBDP is a potential adjuvant chemotherapeutic agent for treating pancreatic cancer.

Preoperative peripheral blood neutrophil count predicts long-term outcomes following hepatic resection for colorectal liver metastases.

Preoperative systemic inflammatory response is associated with a poor long-term prognosis following resection surgery for malignant tumors. Several markers of systemic inflammation have been reported to be associated with the outcome; however, they have not currently been fully investigated. Therefore, the association between preoperative peripheral blood neutrophil count and oncological outcome following hepatic resection for colorectal liver metastasis (CRLM) was retrospectively investigated. The present study comprised 89 patients who had undergone hepatic resection for CRLM between January 2000 and March 2010. The association between preoperative peripheral blood neutrophil count and disease-free survival, in addition to overall survival, was investigated. In multivariate analysis, the presence of neoadjuvant chemotherapy (P=0.015), bilobar distribution (P=0.015) and neutrophil count ≥3,500/µl (P=0.025) were independent and significant predictors of poor disease-free survival, while significant predictors of poor overall survival consisted of >4 lymph node metastases (P=0.001), neo-adjuvant chemotherapy (P=0.003), bilobar distribution (P=0.039) and neutrophil count ≥3,500/µl (P=0.040). Additionally, tumor diameter (P=0.021) and monocyte count (P<0.0001) were observed to be significantly greater in the elevated neutrophil count group. In conclusion, preoperative peripheral blood neutrophil count may be an independent and significant indicator of poor long-term outcomes in patients with CRLM following hepatic resection.

IL1 Receptor Antagonist Inhibits Pancreatic Cancer Growth by Abrogating NF-κB Activation.

PURPOSE: Constitutive NF-κB activation is identified in about 70% of pancreatic ductal adenocarcinoma (PDAC) cases and is required for oncogenic KRAS-induced PDAC development in mouse models. We sought to determine whether targeting IL-1α pathway would inhibit NF-κB activity and thus suppress PDAC cell growth. EXPERIMENTAL DESIGN: We determined whether anakinra, a human IL-1 receptor (rhIL-1R) antagonist, inhibited NF-κB activation. Assays for cell proliferation, migration, and invasion were performed with rhIL-1R antagonist using the human PDAC cell lines AsPc1, Colo357, MiaPaCa-2, and HPNE/K-ras(G12V)/p16sh. In vivo NF-κB activation-dependent tumorigenesis was assayed using an orthotopic nude mouse model (n = 20, 5 per group) treated with a combination of gemcitabine and rhIL-1RA. RESULTS: rhIL-1R antagonist treatment led to a significant decrease in NF-κB activity. PDAC cells treated with rhIL-1R antagonist plus gemcitabine reduced proliferation, migration, and invasion as compared with single gemcitabine treatment. In nude mice, rhIL-1R antagonist plus gemcitabine significantly reduced the tumor burden (gemcitabine plus rhIL-1RA vs. control, P = 0.014). CONCLUSIONS: We found that anakinra, an FDA-approved drug that inhibits IL-1 receptor (IL-1R), when given with or without gemcitabine, can reduce tumor growth by inhibiting IL1α-induced NF-κB activity; this result suggests that it is a useful therapeutic approach for PDAC.

Assessment of Graft Selection Criteria in Living-Donor Liver Transplantation: The Jikei Experience.

In living-donor liver transplantation, graft selection is especially important for the safety of the live donor and an acceptable outcome for the recipient. The essential medical requirements for living liver donation at Jikei University Hospital are as follows: an adult aged 65 years or younger, in good general condition, with partial liver volume of more than 35% of the standard liver volume (SLV) for the recipient, and without severe liver steatosis. Based on our criteria, we performed 13 living-donor liver transplantations between 2007 and 2013, including 1 retransplantation. Three cases were outside our standard donor criteria, including age (18 and 66 years) and 33% graft volume (GV) to SLV ratio for the recipient on preoperative volumetry using computed tomography. In 2 cases, the actual GV to SLV ratio at transplantation was less than 35%. Median postoperative hospital stay was 11 days for the donors, and 29 days for the recipients. All donors returned to their preoperative status, and all recipients were discharged in good condition. Our medical requirements for living liver donation seem to be acceptable because of the good outcome.