[A Case of Sigmoid Colon Cancer with Intussusception Prolapsing through the Anus].

A 76-year-old woman presented to the hospital with the colon prolapsing through the anus. The enhanced abdominal computed tomography(CT)showed intussusception of the sigmoid colon due to sigmoid colon cancer. It was difficult to reduce the intussusception, and we did not recognize the ileus and ischemic change of the colon. Therefore, we performed an elective surgery. Hartmann's procedure and lymph node dissection were performed 8 days after the hospitalization. The postoperative course was uneventful. We report a case of sigmoid colon cancer with intussusception prolapsing through the anus.

[A Case of Complete Resection Using the Liver-First Approach after Systemic Chemotherapy in a Patient with Synchronous Colorectal Liver and Lung Metastases].

Conversion surgery for patients with initially unresectable colorectal liver metastases is increasingly being performed because of effective systemic chemotherapy. Additionally, many studies have reported the benefit of the liver-first approach for advanced liver metastasis. We report a case of an initially unresectable advanced colon cancer with multiple liver and lung metastases that was successfully treated with the liver-first approach following chemotherapy. The patient was a 36-year- old woman who was diagnosed with advanced rectal cancer, cT4aN2aM1b, cStage Ⅳb. After a temporary transverse colostomy, she was administered systemic chemotherapy for 9 months. The primary tumor and liver metastases showed partial response while the lung metastases showed complete response. Since it was considered that liver metastases were the main prognostic factors, we performed a right hemihepatectomy plus S3 partial hepatectomy, followed by laparoscopic high anterior resection. A partial pneumonectomy was also performed because of the regrowth of the lung metastases, and we succeeded in complete resection. The liver-first approach was a beneficial treatment option for this patient with unresectable colorectal liver metastases.

Preoperative neutrophil-to-lymphocyte ratio as a predictor of survival after reductive surgery plus percutaneous isolated hepatic perfusion for hepatocellular carcinoma: a retrospective analysis.

PURPOSE: We assessed the predictive value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients who underwent a two-stage treatment combining reductive surgery and percutaneous isolated hepatic perfusion for multiple hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: Forty-two patients underwent the two-stage treatment between January 2000 and December 2014 at Kobe University Hospital (Hyogo, Japan). The NLR was calculated from lymphocyte and neutrophil counts in the preoperative routine blood test. Clinical data and overall survival were compared statistically and multivariate analysis was done to identify prognostic factors. RESULTS: The median survival of patients with a preoperative NLR > 2.3 was 14.9 months (n = 13), whereas that of patients with a preoperative NLR ≤ 2.3 was 26.1 months (n = 29; P = 0.022). A preoperative NLR > 2.3 was an independent prognostic factor in patients with multiple HCC with PVTT [hazard ratio (HR) 2.329; 95 % confidence interval (CI) 1.058-5.667; P = 0.036]. CONCLUSION: Based on the results of this study, an elevated preoperative NLR is an independent predictive risk factor for patients undergoing two-stage treatment for multiple HCC with PVTT.

Anatomical variations of liver blood supply in patients with pancreaticobiliary maljunction.

PURPOSE: Pancreaticobiliary maljunction (PBM) arises from a developmental abnormality during the embryonic period; thus, these patients may have anatomical variations of the liver blood supply, including aberrant vessels and unusual locations. METHODS: We reviewed retrospectively the vascular anatomy of 52 patients with PBM, who were seen between 1998 and 2013. RESULTS: There were 11 male patients and 41 female patients. Sixteen patients had bile duct type (C-P type) PBM, 35 had pancreatic duct type (P-C type) PBM, and one had complex type PBM. Thirty-three patients had biliary dilatation. Nine (17.3 %) patients had an aberrant (replaced or accessory) hepatic artery and 2 (3.8 %) had an aberrant portal vein. Among 39 patients evaluated by contrast-enhanced computed tomography, 8 (20.5 %) had their right hepatic artery positioned on the ventral side of the common bile duct. The presence of aberrant hepatic vessels was not related to the type of confluence, biliary dilatation, type of Todani classification, or associated biliary malignancies. CONCLUSIONS: The incidence of the right hepatic artery being located on the ventral side of the common bile duct may be higher in patients with PBM than the naturally occurring incidence of about 10 % in the general Japanese population.

[A Case of Recurrent Ovarian Fibrosarcoma Resected by Pancreaticoduodenectomy].

A 66-year-old woman presented to the Department of Gynecology in our institution in 2005 with peritoneal recurrence of ovarian fibrosarcoma. Originally, combined modality therapy including repeated surgical resection and somatic chemotherapy was performed. A peritoneal recurrence was found near the pancreatic head. She was referred to our department in October 2015, and underwent pancreaticoduodenectomy. The tumor was severely adhesive to the portal vein and combined portal venous resection was performed. Histological examination of tumor specimens revealed tumor invasion to the adjacent pancreatic parenchyma and portal vein. No evidence of recurrence was detected after a follow-up of 8 months. We suggest that in cases with peritoneal recurrence of ovarian tumors, radical resection might be considered, taking into account the biologic behavior of the tumor.

[A Case of Pancreatic Metastasis of Osteosarcoma Resected Using Laparoscopic Spleen Preserving Distal Pancreatectomy].

A 44-year-old woman underwent surgical resection and received preoperative and postoperative chemotherapy for conventional osteosarcoma in the right fibular head. Three years later, follow-up PET-CT revealed accumulation ofFDG in the tail ofthe pancreas. Contrast-enhanced computed tomography showed a 13mm well-circumscribed hypovascular tumor. EUS showed a heterogeneous solid tumor, which was diagnosed as metastasis ofosteosarcoma to the pancreas. Laparoscopic spleen preserving distal pancreatectomy(LAP-SPDP)was performed. Pathologically, the tumor was diagnosed as metastasis ofconventional osteosarcoma to the pancreas. Cells from pancreas islet tissue were detected in the tumor, suggesting invasion ofthe tumor into the pancreatic body and surrounding adipose tissue. Although postoperative chemotherapy was administered, lung metastasis was detected 1.1 years after surgery. Laparoscopic partial resection of the lung metastasis was performed, and the patient is still alive. Metastasis ofosteosarcoma to the pancreas is rare, and there is no report oflaparoscopic approach as a treatment. Herein, we report a case with several references.

Alendronate attenuates eosinophilic airway inflammation associated with suppression of Th2 cytokines, Th17 cytokines, and eotaxin-2.

Bisphosphonates (BPs) have been widely used to treat osteoporosis. They act by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. This resembles the action of statins, whose immune-modulating effect has recently been highlighted. In contrast, the effect of BPs on immune responses has not been elucidated well. In this study, we examined the effect of alendronate (ALN), a nitrogen-containing BP, on allergic airway inflammation in a mouse model. BALB/c mice were sensitized twice with OVA and challenged three times with nebulized OVA to induce eosinophilic airway inflammation. ALN was administered by an intragastric tube before each inhalation. ALN strongly suppressed airway eosinophilia and Th2, as well as Th17 cytokine production in the lung. ALN also attenuated eotaxin-2 production in the lung. Immunohistochemistry demonstrated that the major cell source of eotaxin-2 was peribronchial/perivascular macrophages, and flow cytometrical studies confirmed that ALN decreased eotaxin-2 expression in these macrophages. Furthermore, ALN attenuated eotaxin-2 production from mouse pleural macrophages and human monocyte/macrophage-like THP-1 cells in vitro. These results suggest that ALN suppressed Ag-induced airway responses in the mouse model. The suppression of eotaxin-2 production from macrophages appears to be one of ALN's immunomodulatory effects, whereas the mechanism by which ALN suppressed Th2 and Th17 responses could not be fully elucidated in this study. Although a clinical study should be conducted, ALN could be a novel therapeutic option for asthma.

[Resection of Initially Unresectable Gallbladder Cancer with Multiple Liver Metastases after Chemotherapy with Gemcitabine plus Cisplatin].

A 61-year-old woman was referred to our hospital for surgery for gallstones. She was diagnosed as having gallbladder cancer after a detailed radiologic examination. At the first laparotomy, gallbladder cancer with bulky invasion to the liver and multiple liver metastases were observed. Gemcitabine plus cisplatin (GC) administration was chosen. After 7 administration of GC, we changed GC to gemcitabine alone due to blood toxicity. After 7 months of chemotherapy, although CT findings showed regression of the liver invasion and the liver metastases, the serum CA19-9 level gradually increased. Because there were no obvious distant metastases on detailed radiologic examination, we performed surgery for the primary lesion after obtaining informed consent. Pathological examination demonstrated fibrosis without viable cancer cells in the metastatic liver tumor. Gemcitabine was administered as post-operative adjuvant chemotherapy. Twelve months after surgery, there was no sign of recurrence.

[A Case of Invasive Intraductal Papillary Mucinous Carcinoma, Penetrating the Stomach, Colon, and Jejunum].

A 69-year-old woman was admitted to a nearby clinic complaining of abdominal pain. Abdominal CT showed a 10 cm diameter huge cystic lesion in the body and tail of the pancreas. The patient was referred to our institution for treatment. Endoscopic ultrasonography (EUS) revealed a cystic mass with a solid lesion. Endoscopic retrograde pancreatography(ERP) demonstrated mucous at the opening of the papilla of Vater and dilatation of the pancreatic duct with a solid nodule. Contrast radiography revealed a fistula from the tumor to the jejunum. A biopsy specimen from the lesion showed adenocarcinoma. Intraoperative findings showed a tumor occupying the pancreas body and tail with suspected invasion to the stomach, jejunum, and transverse colon. We performed distal pancreatectomy with partial resection of stomach, jejunum, and colon. Pathological findings showed an invasive type of IPMC, with invasion to the subserosal layer of the stomach and colon and the mucous layer of the jejunum. While IPMC is recognized as a slow growing malignancy, some cases of invasive carcinoma with fistulation into adjacent organs have been reported. To our knowledge, a case of IPMC penetrating to 3 adjacent organs is rare.

[Long-term survivor of unresectable bile duct cancer complicated with sclerosing cholangitis treated with chemotherapy].

A 70-year-old woman was admitted to a near by hospital with complaints of epigastric pain and fever. Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) revealed stenosis of the hilar bile duct and multiple stenoses in the intrahepatic bile duct; bile cytological analysis indicated adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were within normal limits. It was very difficult to evaluate the extent of tumor invasion; therefore, we concluded that the tumor was unresectable. The patient underwent systemic chemotherapy with gemcitabine. After 5 years, she developed obstructive jaundice and cholangitis. The patient underwent endoscopic retrograde biliary drainage (ERBD), with 3 incidents of cholangitis recurrence. Although systemic chemotherapy with gemcitabine was performed for a long time, she died 6 years after the initiation of chemotherapy. Gemcitabine was administered 140 times in total, with a total dose of 203.744 g.

[Re-resection for recurrent intrahepatic cholangiocarcinoma].

INTRODUCTION: The benefits of re-resection for recurrent intrahepatic cholangiocarcinoma (IHC) are unknown. PATIENTS AND METHODS: We evaluated the comparative efficacy of different treatment schema for recurrent IHC following curative resection. RESULTS: Among 46 patients, 26 underwent R0 resection, while 20 underwent R1 resection. There were 13 cases of recurrence in R1 patients (65%), and 19 in R0 patients (61%). Recurrent IHC cases were divided into 3 groups based on the treatment received after recurrence: re-resection (n=5), chemotherapy (n=13), and best supportive care (BSC) (n=8). Survival times were evaluated for each group; median survival times (MSTs) after recurrence were 26, 14, and 4 months for the re-resection, chemotherapy, and BSC groups, respectively (p=0.030). Next, we examined the patients who only had intrahepatic recurrence; MSTs after recurrence for re-resection, chemotherapy, and BSC groups were 26, 14, and 5 months, respectively (p=0.0018). CONCLUSION: In recurrent IHC, survival time improves with re-resection or chemotherapy, when compared to BSC. In patients with intrahepatic recurrence only, re-resection is especially effective in prolonging survival.

[A case of resection of a metastatic liver tumor that recurred after particle beam therapy].

Recently, the indications for particle beam therapy have been expanded to include metastatic liver tumors. However, its adverse effects on the treated liver are unclear, and the possibility of local recurrence after treatment should not be ignored. A 65-year-old man with advanced rectal carcinoma underwent low anterior resection. Resectable metastatic liver tumors were detected after adjuvant chemotherapy; however, he opted to undergo particle beam therapy. Nine months after treatment, a local recurrence was detected around the treated area, and central bisegmentectomy of the liver was performed as a salvage operation. The operation was technically complicated owing to severe adhesions and inflammatory changes in the liver parenchyma around the treated area. Pathological examination revealed advanced liver fibrosis at the treated area, in contrast with normal parenchyma in the untreated area. Although the procedure requires advanced surgical techniques, salvage surgery is a feasible option for recurrent liver tumors after particle beam therapy.

[Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy].

Here, we report a case of Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy. A 69-year old man underwent pancreatoduodenectomy for pancreatic cancer in 2006 in which the splenic vein was ligated near the portal vein and then divided. The patient suffered repeated episodes of anemia between 2010 and 2013. However, we could not identify the bleeding site at that time. In 2011, local recurrence was detected. Disease progression occurred despite chemotherapy treatment, which was then discontinued. The left-sided portal hypertension gradually progressed, and the collateral vessels became dilated. In 2014, he was examined in our department for gastrointestinal bleeding. An upper gastrointestinal endoscopy revealed bleeding from gastric varices. Gastrointestinal bleeding ceased after endoscopic injection sclerotherapy ( EIS) was performed; however, the bleeding recurred. Balloon retrograde transvenous occlusion (BRTO) could not be performed because blood flow was not detected within the gastro-renal shunt. An emergency surgery was performed. Surgical splenectomy and devascularization (Hassab's operation) were performed. After surgery, the gastric body varices and gastrointestinal anastomosis disappeared and the bleeding did not occur. He is currently receiving outpatient treatment.

High expression of IL-22 suppresses antigen-induced immune responses and eosinophilic airway inflammation via an IL-10-associated mechanism.

Allergic inflammation in the airway is generally considered a Th2-type immune response. However, Th17-type immune responses also play important roles in this process, especially in the pathogenesis of severe asthma. IL-22 is a Th17-type cytokine and thus might play roles in the development of allergic airway inflammation. There is increasing evidence that IL-22 can act as a proinflammatory or anti-inflammatory cytokine depending on the inflammatory context. However, its role in Ag-induced immune responses is not well understood. This study examined whether IL-22 could suppress allergic airway inflammation and its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IL-22-producing plasmid vector was delivered before the systemic sensitization or immediately before the airway challenge. Delivery of the IL-22 gene before sensitization, but not immediately before challenge, suppressed eosinophilic airway inflammation. IL-22 gene delivery suppressed Ag-induced proliferation and overall cytokine production in CD4(+) T cells, indicating that it could suppress Ag-induced T cell priming. Antagonism of IL-22 by IL-22-binding protein abolished IL-22-induced immune suppression, suggesting that IL-22 protein itself played an essential role. IL-22 gene delivery neither increased regulatory T cells nor suppressed dendritic cell functions. The suppression by IL-22 was abolished by deletion of the IL-10 gene or neutralization of the IL-10 protein. Finally, IL-22 gene delivery increased IL-10 production in draining lymph nodes. These findings suggested that IL-22 could have an immunosuppressive effect during the early stage of an immune response. Furthermore, IL-10 plays an important role in the immune suppression by IL-22.

IFN-gamma attenuates antigen-induced overall immune response in the airway as a Th1-type immune regulatory cytokine.

Allergic inflammation in the airway is generally considered a Th2-type immune response. However, recent studies demonstrated that Th1- and Th17-type immune responses also play important roles in this process. IFN-gamma is a Th1-type cytokine that generally counteracts the Th2 response. Although previous studies suggest that exogenous IFN-gamma suppresses allergic airway inflammation, the mechanism of suppression has not been fully clarified. In this study, we elucidated whether IFN-gamma suppresses Ag-induced immune responses including the production of Th1- and Th17-type cytokines in the lung, and examined its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IFN-gamma-producing plasmid vector was delivered before systemic Ag sensitization. IFN-gamma suppressed indicators of Th2-type immune responses such as airway eosinophilia, IL-5 and IL-13 production in the lung, and bronchial mucus production. Moreover, IFN-gamma also suppressed the production of IL-17 and IFN-gamma itself. The suppression was not mediated by inducing regulatory T cells or by inducing apoptosis in immunocytes. Instead, IFN-gamma suppressed the Ag-presenting capacity and cytokine production of splenic dendritic cells and thus subsequently suppressed OVA-induced activation of CD4(+) T cells. Furthermore, IFN-gamma also attenuated allergic airway inflammation when delivered during the OVA challenge. Various functions of lung CD11c(+) APCs and their migration to regional lymph nodes were also suppressed. These results suggest that the Th1 cytokine IFN-gamma has broad immune regulatory potential through suppressing APC functions. They also suggest that delivery of IFN-gamma could be an effective strategy for regulating Ag-induced immune responses in the lung.

Hepatocellular carcinoma recurrence in the extrahepatic bile duct wall: A case report.

We should know that hepatocellular carcinoma can progress as if it replaces the bile duct wall itself.

A case of intraductal papillary neoplasm of the bile duct accompanied by intraductal papillary mucinous neoplasm of the pancreas and hepatocellular carcinoma.

A 73-year-old man with mixed-type intraductal papillary mucinous neoplasm of the pancreas body was followed up for 14 years. Based on imaging findings, the intraductal papillary mucinous neoplasm of the pancreas met the high-risk stigmata, and new hepatic masses were suspected to be intraductal papillary neoplasms of the bile duct. With a diagnosis of intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct, the patient had undergone left lateral hepatectomy and distal pancreatectomy. Based on pathology, the pancreatic specimen was diagnosed as a high-grade intraductal papillary mucinous neoplasm of the pancreas, and the hepatic specimen was diagnosed as an intraductal papillary neoplasm of the bile duct and hepatocellular carcinoma. The intraductal papillary neoplasms of the bile duct and hepatocellular carcinoma were adjacent to each other. Fifteen months after surgery, recurrence in the remnant pancreas was detected. The patient had undergone residual total pancreatectomy, with no recurrence thirty months after the second resection. This case demonstrates that second surgery for metachronous high-risk lesions in the remnant pancreas of patients with intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct may also be considered to improve survival.

A case of laparoscopic anterior resection for rectal cancer with duplication of the inferior vena cava using preoperative 3D computed tomography angiography.

We report the case of a patient with duplication of the inferior vena cava (DIVC) who underwent anterior laparoscopic resection for rectal cancer. A 66-year-old woman presented with abnormal lung shadows on a chest x-ray during a routine health checkup. She was diagnosed with rectal cancer and lung metastasis using colonoscopy and thoracoabdominal computed tomography (CT). In addition, a 3D CT angiography revealed double inferior vena cava, one on either side of the aorta. The preoperative diagnosis was rectal cancer cT3N0M1a(Lung) cStage IVA with DIVC, and a two-stage surgery was planned. The first stage was high anterior laparoscopic resection. This was safely performed because the pre-hypogastric nerve fascia was preserved and the left inferior vena cava was not visualized during the surgery. During the second stage of the surgery, video-assisted thoracoscopic left lower lobectomy was performed and no recurrence was observed for >6 months after the second surgery.

Upregulation of lung dendritic cell functions in elastase-induced emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is now considered a chronic inflammatory disease. Although dendritic cells (DCs) are thought to play a key role in immune responses, studies investigating the role of DCs in COPD are quite limited. METHODS: Porcine pancreas elastase was intratracheally administered to C57BL/6J mice on day 0. On days 2, 7 and 14, emphysema formation was evaluated by pressure-volume relationships and microscopic findings, including measurement of the mean linear intercept. Lung DCs were isolated on day 2, and their ability to stimulate allogeneic T cells and to produce cytokines was examined. RESULTS: Pathologic emphysematous change was observed on day 2 and a significant increase in lung volume was observed on day 14. Lung DC function, such as the induction of T-cell proliferation and IL-10 production, was upregulated. CONCLUSIONS: Upregulation of DC function was observed in elastase-induced emphysema. Further investigation on the contribution to emphysema formation may provide a useful target for future therapy.

Intratracheal delivery of hepatocyte growth factor directly attenuates allergic airway inflammation in mice.

Hepatocyte growth factor (HGF) has an important role in many biological events such as angiogenesis and cell proliferation, as well as anti-fibrotic and anti-apoptotic effects. In addition, we found that HGF suppresses antigen-induced immune responses in the airway by suppressing dendritic cell functions, using a HGF-producing plasmid vector. In the present study, we examined whether delivery of the HGF protein in the lung attenuates allergic airway inflammation in a mouse model. Generally, HGF is rapidly cleared from organs. So, to achieve the efficient delivery of HGF, we prepared a slow-releasing form by mounting recombinant human (rh) HGF protein in biodegradable gelatin hydrogels. BALB/c mice were immunized and then challenged with ovalbumin (OVA) to induce eosinophilic airway inflammation. Intratracheal delivery of a very small amount of gelatin-coupled rhHGF (0.3 microg) just once before the inhalation of OVA significantly suppressed eosinophilic airway inflammation. In addition, cytokine production in thoracic lymph nodes and the antigen-presenting capacity of lung CD11c+ cells were reduced. In contrast, delivery of 1.0 microg of rhHGF did not exhibit any significantly suppressive effect. These results suggest that the controlled release of rhHGF protein can suppress antigen-induced allergic immune responses in the lung. Therefore, HGF could be a novel therapeutic option for asthma.