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Background An open abdomen with frozen adherent bowels is classified as grade 4 in Björck’s open abdomen classification, and skin grafting after wound granulation is a typical closure option. We achieved delayed primary fascia closure for a patient who developed open abdomen with enteroatmospheric fistulas due to severe adherent small bowel obstruction. We present here the details of his management. Case presentation A 52-year-old man suffered acute abdominal pain during a flight and received an emergency laparotomy due to adhesive small bowel obstruction. Repeated laparotomies were required, and later open abdomen and proximal site jejunostomy were selected. After negative pressure wound therapy, he was transferred to our institution. Two enteroatmospheric fistulas emerged on the exposed intestine, and we diagnosed the condition as a Björck grade 4 open abdomen. After 8 months of wound care and parenteral nutrition, we decided to attempt primary wound closure because the patient required permanent oral restriction and total parenteral nutrition due to short bowel syndrome. A circular incision along the circumference of the exposed bowel allowed us to take a safe approach into the abdominal cavity. We removed the intestinal adhesions completely and resected the bowels, including the fistulas and anastomosed parts. Finally, the abdominal wall defect was reconstructed using the component separation technique, and the patient was discharged without an ostomy. Conclusions Primary fascia closure for grade 4 open abdomen is hard, but leaving a long interval before radical surgery and applying pertinent wound management may help solve this adverse situation.

Introduction: Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are specifically expressed on pancreatic cancer cells, and that a protein specifically binding to these glycans, namely rBC2LCN lectin, is a potential guiding drug carrier. In the present study, a novel type of glycan-targeting nanoparticle was developed by modifying the surface of doxorubicin-containing liposomes with rBC2LCN lectin. The efficiency and specificity of this formulation, termed Lec-Doxosome, were examined in vitro and in vivo in human pancreatic cancer models. Methods: Lec-Doxosome was prepared by a post-insertion method based on the insertion of rBC2LCN lectin into the liposomal surface via a lipid linker. The in vitro cellular binding, uptake, and cytotoxicity of Lec-Doxosome were compared with the corresponding parameters in the unmodified liposomes by applying to human pancreatic cancer cell line (Capan-1) with affinity for rBC2LCN lectin. For the in vivo assay, Lec-Doxosome was intravenously injected once per week for a total of 3 weeks into mice bearing subcutaneous tumors. Results: The in vitro application of Lec-Doxosome resulted in a 1.2- to 1.6-fold higher intracellular doxorubicin accumulation and a 1.5-fold stronger cytotoxicity compared with the respective rates of accumulation and cytotoxicity in the unmodified liposomes. In vivo, Lec-Doxosome reduced the mean tumor weight (368 mg) compared with that in mice treated with unmodified liposomes (456 mg), without causing any additional adverse events. Conclusion: It was demonstrated from the results obtained herein that rBC2LCN lectin is a potent modifier, as a means for boosting the efficiency of nanoparticles in the targeting of cancer cell surface glycans.

This study aimed to demonstrate the usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells as a novel in vitro model for clarifying the impact of intestinal drug-metabolizing enzymes and transporters on the intestinal absorption of substrate drugs in humans. Three-dimensional human intestinal spheroids were successfully established from surgical human jejunal specimens and expanded for a long period using L-WRN-conditioned medium, which contains Wnt3a, R-spondin 3, and noggin. The mRNA expression levels of intestinal pharmacokinetics-related genes in the human jejunal spheroid-derived differentiated intestinal epithelial cells were drastically increased over a 5-day period after seeding compared with those in human jejunal spheroids and were approximately the same as those in human jejunal tissue over a culture period of at least 13 days. Activities of typical drug-metabolizing enzymes [cytochrome P450 (CYP) 3A, CYP2C9, uridine 5'-diphospho-glucuronosyltransferase 1A, and carboxylesterase 2] and uptake/efflux transporters [peptide transporter 1/solute carrier

General surgeons are at high risk for work-related musculoskeletal disorders (WRMSDs), especially in their neck and back. The prevalence and risk factors for surgeons' WRMSDs in Japan have not been well surveyed.A cross-sectional questionnaire survey on WRMSDs was conducted among general surgeons in Japan. Surgeons were asked about the presence and degree of neck, shoulder, and back disability in relation to open and laparoscopic surgery.The questionnaire was sent to 174 general surgeons in 21 hospitals and 106 (60.9%) responded. The prevalence of WRMSDs in the last month was 65.1%, and the prevalence at least once in a lifetime was 79.2%. The rate of WRMSDs of the neck and back was higher after open surgery (44.3%, 42.5%) than after laparoscopic surgery (28.2%, 31.1%), but there was no marked difference in shoulder pain. Age was the strongest risk factor for WRMSDs, and the pain scores, prevalence of chronic pain, and rate of WRMSD-related absence from work tended to increase with age.A questionnaire survey of surgeons in Japan showed that about 80% of surgeons suffer from WRMSDs. Countermeasures for WRMSDs among surgeons are urgently desired to ensure that limited numbers of surgeons work in the operating theatre throughout their career.Registry name: a survey of surgeons' musculoskeletal pain associated with performing surgery. University of Tsukuba Institutional Review Board registration number: 1519.

A 74-year-old man presented to our hospital because of anorexia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer. Further examination disclosed metastasis to the perigastric lymph nodes and to the liver, and a diagnosis of non- resectable advanced gastric cancer(cT4N2H1P0M0)in cStage Ⅳ was made. A total of 4 courses of S-1 plus oxaliplatin therapy(80 mg/body/day and 100 mg/m2/cycle, respectively, for 2 weeks followed by a 1-week rest)were administered as the primary chemotherapy. Then, another metastasis to the abdominal lymph nodes and increased liver metastasis were found; thus, the patient's condition was rated as progressive disease(PD). Secondary chemotherapy comprising 10 courses of weekly nab-paclitaxel(nab-PTX)plus ramucirumab(RAM)therapy(100 mg/m2 on days 1, 8, and 15 and 8 mg/kg on days 1 and 15, respectively, every 4 weeks)were administered. Although temporary reductions in the perigastric lymph node metastasis and liver metastasis as compared with the baseline were observed, another metastasis to the abdominal lymph nodes occurred subsequently, resulting in PD. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 3 weeks) was repeated up to a total of 30 courses over 13 months. This therapy was markedly effective, achieving a near complete response. The patient is currently being followed up as an outpatient.

Controlling portal vein pressure in living-donor liver transplantation has received increased attention owing to its potential importance for graft survival. Portal hypertension may lead to the activation of liver-resident APCs, including liver sinusoidal endothelial cells (LSECs), which have immunological tolerogenic capacity. We investigated the effects of portal hypertension on graft survival and the antidonor immune response using clinical data and a mouse model. We categorized patients (n = 136) according to their portal vein pressure values at the end of surgery. Using propensity score-matching analyses, we found that portal hypertension was significantly associated with a higher antidonor immune response and incidence of acute rejection. To investigate the mechanism, we performed an allogeneic coculture assay using a 70% hepatectomized (HTx) mouse model with or without a portosystemic shunt. Liver cells from HTx mice without a shunt exhibited a significantly greater anti-BALB/c B6 T cell response than those from sham-operated mice or HTx mice with a shunt. LSECs from sham-operated mice, but not from HTx mice, suppressed the B6 T cell alloresponse in a dose-dependent manner. Furthermore, LSECs from HTx mice without a shunt showed significantly downregulated MHC class I/II and programmed death-ligand 1 expression, and those from mice with a shunt showed recovered expression of these molecules. Postoperative portal hypertension enhances alloimmune responses in recipients after living-donor liver transplantation, likely due, in part, to the impaired immune-suppression capacity of LSECs.

Refractory ascites after liver transplant commonly occurs in living donor liver transplant (LDLT). Refractory ascites is associated with postoperative complications and poor prognosis. This study sought to determine the risk factors of refractory ascites and discuss their perioperative management.A retrospective study of 122 living donor liver transplant recipients between 2008 and 2017 was performed to analyze the risk factors, incidence, and characteristics of refractory ascites. Refractory ascites post LDLT was defined as the production of ascites fluid1000 mL/d on postoperative day 14 or required repeated drainage.A total of 24 patients (19.6%) developed refractory ascites. The 1-year survival rate was significantly worse in the refractory ascites group compared with the nonrefractory ascites group (P .001). In a univariate analysis, patients with refractory ascites had a higher Model for End-Stage Liver Disease (MELD) score, donor age, presence of left lobe graft, ascites at laparotomy, portal venous pressure just after surgery, cold ischemia time, and absence of hepatocellular carcinoma compared with patients without refractory ascites. Multivariate proportional regression analyses revealed that MELD score ≥20, left lobe graft, donor age 50 years or older, and ascites at laparotomy ≥350 mL were independently associated with refractory ascites. Postoperative complications, such as bleeding (P .001), sepsis (P .001), and bloodstream infection within 30 days after LDLT (P .00), were significantly higher in the refractory ascites group.Refractory ascites is associated with reduced 1-year survival and increased postoperative complications. Four factors including MELD score ≥20, donor age 50 years or older, presence of left graft, and ascites at laparotomy ≥350 mL were independent predictors for refractory ascites.

Background Mediastinoscope and laparoscope-assisted esophagectomy for esophageal cancer occasionally causes postoperative accumulation of pleural effusion despite the preservation of the mediastinal pleura. Transhiatal chest drainage has been reported to be useful for thoracic esophagectomy; however, its use in mediastinoscope and laparoscope-assisted esophagectomy remains unelucidated. This study aimed to evaluate the effectiveness and safety of transhiatal chest drainage in mediastinoscope and laparoscope-assisted esophagectomy. Methods This retrospective study included patients who underwent mediastinoscope and laparoscope-assisted esophagectomy for esophageal cancer from 2018 to 2021. Transhiatal chest drainage involved the insertion of a 19-Fr Blake® drain from the abdomen to the left thoracic cavity through the hiatus. We assessed its effectiveness and safety by the daily drainage output, accumulation of postoperative pleural effusion, frequency of postoperative thoracentesis, and other complications. The drainage group comprising 24 patients was compared with the non-drainage group comprising 13 patients, in whom a transhiatal chest drainage tube was not placed during mediastinoscope and laparoscope-assisted esophagectomy. Results The median daily output of the transhiatal chest drainage was 230 mL on day 1, 385 mL on day 2, and 313 mL on day 3. The number of patients with postoperative pleural effusion was significantly reduced from 10/13 (76.9%) in the non-drainage group to 4/24 (16.7%) in the drainage group (p = 0.001). The frequency of thoracentesis in the drainage group was significantly lower than that in the non-drainage group (p = 0.002). There were no significant differences in the occurrence of other postoperative complications. Conclusions Transhiatal chest drainage could evacuate pleural effusion effectively and safely after mediastinoscope and laparoscope-assisted esophagectomy.

Background Persistent pancreatic leakage (PL) due to disconnected pancreatic duct syndrome (DPDS) is associated with severe morbidity and mortality and it usually treated with internal drainage. However, in cases without localized fistula formation, internal drainage is challenging to perform. We report an original one-stage surgical approach for nonlocalized persistent PL, namely, the “intentional internal drainage tube method”. Case presentation A 49-year-old woman whose main pancreatic duct was penetrated during endoscopic retrograde cholangiopancreatography experienced severe PL. Peritoneal lavage and a second operation involving central pancreatectomy failed to relieve the symptoms, and nonlocalized PL persisted due to DPDS. Although we attempted a radical resection of the pancreatic remnants as a third strategy, the highly inflamed tissue and massive bleeding prevented the completion of the procedure. We sutured the pancreatic head margin and performed a pancreaticojejunostomy to the distal margin. Because these two cut margins could possibly be the source of the persistent PL, we created a hole at the Roux-en-Y jejunal limb, and a silicone drainage tube was inserted into the peritoneal space via this hole. Postoperatively, we continuously suctioned the intentional internal drainage tube, and the residual PL cavity gradually diminished. Even after removal of the tube, the residual PL drained internally into the jejunum through this hole. Conclusions We present this intentional internal drainage tube method as a novel alternative approach for the management of nonlocalized PL consequential of DPDS. Due to the simplicity and minimally invasive nature of this method, we propose this technique may also be used to treat various types of nonlocalized persistent PL or be used prophylactically for central pancreatectomy.

Background Various minimally invasive surgery (MIS) procedures are used for gastric submucosal tumors (SMTs), and their technical difficulties vary. Preoperative understanding of difficulties is crucial; however, objective indicators are lacking. Methods Gastric SMTs requiring MIS (n = 36) were retrospectively analyzed. Preoperative factors were evaluated using a multivariate linear regression analysis. A scoring system was then constructed, and its feasibility was evaluated. Results Three factors were identified and scored based on the weighted contribution for predicting surgical time: tumor location (cardia, score of “2”; posterior wall of fundus, “1”); tumor size (greater than 4 cm, “1”); and tumor growth appearance (intraluminal, “1”). The summed scores could stratify the surgical time stepwise in each score, and patients who scored higher than 3 had larger intraoperative blood loss and a longer hospital stay. Conclusion Our scoring system predicted surgical difficulties and may, therefore, be useful in selecting appropriate surgical approaches for gastric SMTs.

This is the first study to compare the long-term outcomes between neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy for locally advanced esophageal squamous cell carcinoma. We reviewed patients with clinical stage IB–III esophageal squamous cell carcinoma (UICC 7th edition) who underwent neoadjuvant chemotherapy + surgery or definitive chemoradiotherapy with proton beam therapy (2009–2017). Overall survival, progression-free survival, and recurrence or regrowth rates were compared between the two treatment groups. Subgroup analyses of overall survival according to baseline characteristics were also performed. Forty-three patients received neoadjuvant chemotherapy + surgery (median follow-up 47.4 months) and 60 received definitive chemoradiotherapy with proton beam therapy (median follow-up 51.5 months). Baseline characteristics were similar between the groups except for sex, tumor location, and cT classification. The neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy groups had similar 3-year overall survival rates (73.1% and 61.7%, respectively, hazard ratio: 0.88, 95% confidence interval 0.49–1.58, p = 0.66), 3-year progression-free survival rates (46.5% and 45%, respectively, hazard ratio: 1.03, 95% confidence interval 0.62–1.70, p = 0.92), and recurrence or regrowth rates (53.5% vs. 50.0%, p = 0.84). In the subgroup analysis, favorable survival was observed after definitive chemoradiotherapy with proton beam therapy for cT1–2 disease (hazard ratio 2.58, 95% confidence interval 0.84–7.99) and after neoadjuvant chemotherapy + surgery for cT3 or higher disease (hazard ratio 0.32, 95% confidence interval 0.15–0.67, p-for-interaction = 0.002). Long-term outcomes were comparable between the treatments. The choice of the treatment according to cT classification might affect survival.

Background Present treatment strategy for unresectable locally advanced (UR-LA) pancreatic ductal adenocarcinoma (PDAC) patients is controversial. Hence, a triple-modal therapy, which is a multidisciplinary strategy, was designed for patients with UR-LA PDAC by adding hyperthermia to conventional chemoradiotherapy at our institution. In this study we aimed to evaluate the effectiveness of this strategy. Methods Data of 21 UR-LA PDAC patients who underwent the triple-modal treatment were retrospectively analyzed for evaluating the safety and oncological effect of the treatment. The treatment schedule included, five concurrent infusions of gemcitabine (800 mg/m2) followed by hyperthermia (1 h) and X-ray (2 Gy) or proton beam radiation (2.7 Gy) on days 1, 8, 15, 29, and 36. Additional radiotherapies applied a total dose of 50 Gy/25 fr for X-ray radiation or 67.5 Gy/25 fr for proton beam radiation. Results Median overall survival (OS) was 23.6 months. Conversion surgery was performed in 5 patients (23.8%), and a R0 margin could be achieved in 4 of them; however, their median OS (16.3 months) tended to be shorter than that of the patients who did not undergo resection (23.6 months, p = 0.562). Further, the median OS of patients who underwent proton beam radiation (28.0 months) was significantly longer than that of patients who underwent X-ray radiation (13.9 months, p = 0.045). Most adverse events were manageable, except for one grade 3 gastric ulcer. The median tumor size and marker reduction rates were −17% and −91%, respectively. The tumor responses were partial response, stable disease, and progressive disease in 3, 15, and 3 patients, respectively. Conclusion Triple-modal strategy, especially when combined with proton beam radiation, is feasible and results in favorable survival outcomes in patients with UR-LA PDAC.

Introduction Early access failure is an important complication of autogenous arteriovenous fistulas (AVFs). We prospectively monitored patients who underwent AVF creation using ultrasonography. Methods Color flow imaging was used to assess access blood flow in patients undergoing creation of a new AVF in the distal forearm preoperatively and at 1 day and 1 week postoperatively. We measured the flow volume (FV) and resistive index (RI) of the brachial artery, and the internal diameter of the brachial artery and outflow vein. The primary outcome was the primary patency of the AVF without percutaneous angioplasty (PTA) or surgical revision 40 days after access creation. Results We recruited 35 patients with newly created AVFs (men, 21; mean age, 73 years). Within one day of operation, the overall FV increased from 62 to 352 mL/min (pConclusions Access FV and RI at 1 day after AVF creation can predict primary patency and help plan intervention.

Thrombocytosis in patients with various cancers has been considered a parameter for poor prognosis; however, its contribution to pancreatic cancer remains controversial.Potential preoperative prognostic parameters (platelets, neutrophils, lymphocytes, the platelet-lymphocyte ratio, the neutrophil-lymphocyte ratio, the serum C-reactive protein [CRP], and carbohydrate antigen 19-9) were retrospectively analyzed in 95 patients with pancreatic cancer. Cutoff values were defined according to receiver operating characteristic curve analysis, and median survival times (MSTs) were compared.Median survival times (days) significantly differed according to platelet count (high [552] vs low [735], P = 0.017), CRP (high [471] vs low [750], P = 0.001), and carbohydrate antigen 19-9 level (high [639] vs low [765], P = 0.021), whereas there was no difference in the platelet-lymphocyte ratio and the neutrophil-lymphocyte ratio. Multivariate analysis identified thrombocytosis (hazard ratio, 2.015) and CRP level (hazard ratio, 1.771) as independent prognostic factors. The combinatory effects of platelets and the inflammatory response using a platelet × CRP multiplier value could effectively distinguished the MSTs (days) of patients with pancreatic cancer (high [482] vs low [812], P0.001).Thrombocytosis and CRP influenced pancreatic cancer patient prognosis. Platelet × CRP multiplier is assumed as a useful parameter that reflects the contribution of activated platelets to cancer progression.

Delayed gastric emptying (DGE) is a critical complication after pancreaticoduodenectomy (PD). Antecolic gastrojejunostomy has long been adopted as standard procedure because it is thought to reduce DGE. However, we have used retrocolic gastrojejunostomy (retro-GJ) for more than 10 years and have not observed high DGE rates. We aimed to clarify whether our retro-GJ approach produced comparable outcomes in preventing DGE.A total of 211 patients who underwent pylorus-resecting PD with retro-GJ at our institution between 2005 and 2016 were retrospectively analyzed. The incidence rate of DGE and the length of postoperative hospital stay were assessed.The overall incidence of DGE with our retro-GJ procedure was 13% (n = 28), and the rate of clinically relevant DGE (grade B or C based on the International Study Group of Pancreatic Surgery criteria) was 4% (n = 8). The median postoperative hospital stay was 17 days (interquartile range, 13-25 days). Major complications (Clavien-Dindo grade ≥III) occurred in 37% (n = 79) of patients and were not associated with the occurrence of clinically relevant DGE (P = 0.47).Our retro-GJ approach after PD with gastrojejunostomy, which involves careful positioning at the left-sided inframesocolic point, satisfactorily prevents DGE.

Background Celiac axis compression syndrome (CACS) blocks adequate hepatic arterial flow and is a risk factor for hepatic artery thrombosis after liver transplantation. We report a case of living donor liver transplantation in a 65-year-old Brazilian male with liver cirrhosis of Child-Pugh class C and hepatocellular carcinoma caused by hepatitis C virus infection. Results The patient underwent living donor liver transplantation using the graft of his 34-year-old daughter. Stenosis of the celiac artery was detected on preoperative computed tomography (CT), and CACS was suspected. Maintaining blood supply through the hepatic artery to prevent potential graft loss is essential in liver transplantation. A decrease in common hepatic artery (CHA) flow due to CACS could disturb graft blood supply or lead to hepatic artery thrombosis. In this case, we confirmed CACS through dynamic CT and used intraoperative Doppler ultrasonography (US) to plan the surgical procedure. Three types of hepatic artery reconstruction have been described in liver transplantation for CACS, namely the release of the median arcuate ligament (MAL), aorto-hepatic graft reconstructions, and reconstruction preserving the gastroduodenal artery (GDA) without MAL release. We found that clamping the GDA completely abolished hepatic inflow, but clamping the CHA did not change the hepatic inflow. Therefore, we performed arterial reconstruction without division of the GDA. The patient's postoperative course was good, with excellent hepatic artery flow, as assessed by Doppler US. Conclusions Preoperative dynamic CT evaluation, adequate preparation of surgical procedures, and intraoperative evaluation by Doppler US is recommended in liver transplantation patients with CACS.

AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis. METHODS We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin. RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles. CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

Even with current promising antitumor antibodies, their antitumor effects on stroma‐rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa‐2; moderate, BxPC‐3; and abundant, Capan‐1 and Ope‐xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra‐abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa‐2 model, moderate (1063) in the BxPC‐3 model, and negative in the Capan‐1 and Ope‐xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8‐fold (2980, 3015) in the BxPC‐3 model, 2.5‐ or 4.8‐fold (1881, 3615) in the Capan‐1 model, and 3.2‐ or 4.2‐fold (1469, 1922) in the Ope‐xeno model, respectively. Cetuximab was effective in treating even stroma‐rich and k‐ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia.

Among the types of pancreatic anastomosis used after pancreatoduodenectomy (PD), Blumgart type reconstruction has rapidly been distributed for its theoretical reasonableness, including secure tight adaptation of jejunal wall and pancreatic parenchyma without cause of parenchymal laceration. The clinical appropriateness of our modified Blumgart method was demonstrated by comparing to that of Kakita method. Retrospective analysis of 156 patients underwent elective open PD, reconstructed former 78 patients with the Kakita method, utilizing a full-thickness penetrating suture for tight stump adhesion. The later 78 patients were treated with the modified Blumgart method, which involved clamping the pancreatic parenchymal stump by the jejunal seromuscular layers with horizontal mattress-type penetration sutures. Evaluated variables were the rate of pancreatic fistula (PF) and the length of postoperative hospital stay (POHS). The rate of ISGPF grade B + C PF was 29/78 (37.2 %) in the Kakita group and 16/78 (20.5 %) in the Blumgart group (P = 0.033). The median POHS for the Kakita group was 23 days, whereas that for the Blumgart group was 16 days (P

We investigated the anxiolytic effects and mechanism of action of a new anxiolytic drug, (R)-piperonyl-1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine-3- carboxamide hydrochloride (AP521). AP521 showed equal or more potent anxiolytic-like effects compared with diazepam, a benzodiazepine receptor agonist, or tandospirone, a partial 5-hydroxytryptamine (5-HT)1A receptor agonist, in three rat anxiety models; the Vogel-type conflict test, elevated plus maze test, and conditioned fear stress test. Although AP521 did not bind to the benzodiazepine receptor, it did bind to 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5A and 5-HT7 receptors, and showed agonist activity for the human 5-HT1A receptor expressed in HEK293 cells. Tandospirone, which can stimulate the presynaptic 5-HT1A receptors in the raphe, tended to decrease extracellular 5-HT concentration in the medial prefrontal cortex (mPFC) in rats. In contrast, AP521 increased extracellular 5-HT concentration. In addition, AP521 enhanced the anti-freezing effect of citalopram, a selective serotonin reuptake inhibitor, in the fear conditioning model in rats and enhanced the citalopram-caused increase of the extracellular 5-HT concentration in the mPFC. These results suggest that AP521 exhibits potent anxiolytic effects by acting as a postsynaptic 5-HT1A receptor agonist and by enhancing serotonergic neural transmission in the mPFC by a novel mechanism of action.

The development of diagnostic imaging technology, such as multidetector computed tomography (MDCT) and magnetic resonance cholangiopancreatography (MRCP), has made it possible to obtain detailed images of the bile duct. Recent reports have indicated that a 3-dimensional (3D) reconstructed imaging system would be useful for understanding the liver anatomy before surgery. We have investigated a novel method that fuses MDCT and MRCP images. This novel system easily made it possible to detect the anatomical relationship between the vessels and bile duct in the portal hepatis. In this report, we describe a very rare case of extrahepatic cholangiocarcinoma associated with an accessory bile duct from the caudate lobe connecting with the intrapancreatic bile duct. We were unable to preoperatively detect this accessory bile duct using MDCT and MRCP. However, prior to the second operation, we were able to clearly visualise the injured accessory bile duct using our novel 3D imaging modality. In this report, we suggest that this imaging technique can be considered a novel and useful modality for understanding the anatomy of the portal hepatis, including the hilar bile duct.

Background: Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor. Methods: A total of five pancreatic cancer murine models (two cell line-based xenografts (CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg−1, q3d × 4) alone or GEM plus iRGD peptide (8 μmol kg−1). Evaluation of NRP1 expression in xenografts and 48 clinical cancer specimens was performed by immunohistochemistry (IHC). Results: We identified a subset of pancreatic cancer models that showed NRP1 overexpression sensitive to iRGD co-administration. Treatment with GEM plus iRGD peptide resulted in a significant tumour reduction compared with GEM monotherapy in CXs, but not remarkable in TGs. Potential targets of iRGD were characterised as cases showing NRP1 overexpression (IHC-2+/3+), and these accounted for 45.8% of the clinical specimens. Conclusions: Internalised RGD peptide enhances the effects of co-administered drugs in pancreatic cancer models, its efficacy is however only appreciable in those employing cell lines. Therefore, the clinical application needs to be given careful consideration.

CD44(+) /CD24(+) /EpCAM(+) cells have been reported to be cancer stem cells in pancreatic cancer; however, the histological and clinical importance of these cells has not yet been investigated. Here we clarified the characteristics of CD44(+) /CD24(+) /EpCAM(+) cells in clinical specimens of pancreatic cancer using immunohistochemical assay. We used surgical specimens of pancreatic ductal adenocarcinoma from 101 patients. In view of tumor heterogeneity, we randomly selected 10 high-power fields per case, and triple-positive CD44(+) /CD24(+) /EpCAM(+) expression was identified using our scoring system. The distribution, histological characteristics, and prognostic importance of CD44(+) /CD24(+) /EpCAM(+) cells were then analyzed. As a result, the distribution of CD44(+) /CD24(+) /EpCAM(+) cells varied widely among the 101 cases examined, and CD44(+) /CD24(+) /EpCAM(+) expression was correlated with poor glandular differentiation and high proliferation. Survival analysis showed that CD44(+) /CD24(+) /EpCAM(+) expression was not correlated with patient outcome; however, CD44(+) /CD24(+) expression appeared to be correlated with poor prognosis. In conclusion, CD44(+) /CD24(+) /EpCAM(+) expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer. In particular, the presence of double-positive CD44(+) /CD24(+) expression seemed to have clinical relevance, associating with poor prognosis.

Neuroendocrine carcinoma (NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma (cT4N1M0, cStage IV). He underwent a right hepatectomy combined with extrahepatic bile duct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis.

We performed three-dimensional (3D) surgical simulation of pancreatic surgery, including the size and location of the main pancreatic duct on the resected pancreatic surface. The subjects of this retrospective analysis were 162 patients who underwent pancreatic surgery. This cohort was sequentially divided into a “without-3D” group (n = 81) and a “with-3D” group (n = 81). We compared the pancreatic duct diameter and its location, using nine sections in a grid pattern, with the intraoperative findings. The perioperative outcomes were also compared between patients who underwent pancreaticoduodenectomy (PD) and those who underwent distal pancreatectomy (DP). There were no significant differences in the main pancreatic duct diameter between the 3D-simulated values and the operative findings. The 3D-simulated main pancreatic duct location was consistent with its actual location in 80 % of patients (65/81). In comparing the PD and DP groups, the intraoperative blood loss was 1174 ± 867 and 817 ± 925 ml in the without-3D group, and 828 ± 739 and 307 ± 192 ml in the with-3D group, respectively (p = 0.024, 0.026). The 3D surgical simulation provided useful information to promote our understanding of the pancreatic anatomy, including details on the size and location of the main pancreatic duct.

Surgical enterolysis is the final option for patients with encapsulating peritoneal sclerosis (EPS). However, EPS is sometimes refractory to surgical enterolysis. This is the first report of successful use of percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) in a patient with EPS that was refractory to surgical enterolysis. We propose that sustained drainage of digestive juices by PEG-J, along with central venous nourishment at home, can be a treatment option for patients with EPS that cannot be treated with radical measures.

Although chemotherapeutic nanoparticles would confer various advantages, the majority of administrated nanoparticles are known to be spoiled by the reticuloendothelial system (RES). Intending to more effectively deliver therapeutic nanoparticles to target regions in vivo, host RES, especially Kupffer cells in the liver, have been depleted ahead of drug administration. To demonstrate this hypothesis, clodronate liposomes were preinjected into BALB/c nude mice for depletion of Kupffer cells 2 days before, and pegylated liposomal doxorubicin (Doxil) at the doses of 1.25, 2.5 and 5.0 mg/kg was administered. As a result, doxorubicin accumulation in the liver was decreased from 36 to 26% injected dose/organ by the Kupffer cells depletion, and consequently, the plasma concentration of doxorubicin was significantly enhanced threefold (from 11 to 33 μg/mL) on day 1 at 1.25 mg/kg-dose group. Doxorubicin accumulation in the tumor was increased from 0.78 to 3.0 μg/g-tissue on day 3, and tumor growth inhibition by Doxil was significantly boosted (tumor volumes from 751 to 482 mm(3) on day 24) by the Kupffer cells depletion. In conclusion, Kupffer cells depletion by clodronate liposomes enhanced the plasma concentration and antitumor effects of Doxil, and would be widely applicable for various clinical cancer chemotherapies using nanoparticles.

Although induction heating cancer therapy (IHCT) using magnetic nanoparticles can be a promising approach to treatment-less multi-nodular cancers, the objective requirement for successful clinical application has not clearly been elucidated. We intended to define objective heat doses suitable for IHCT, especially focusing on the sizes of liver cancer nodules.Alternating magnetic fields were applied to three human pancreatic cancer cell lines, the intercellular space of those cell pellets were filled with magnetic nanoparticles, and confirmed the cytotoxic effect of IHCT. Subsequently, the temperatures of liver cancer nodules in IHCT were simulated using a computer software program and the required heat dose for various sized tumours were determined.Heating the cancer cells up to 50 degrees C for 10 min was sufficient for complete cell killing and the heat dose of 1.7 W/g(tumour) is required for 10 mm tumour. Larger tumours require a smaller heat dose, e.g. 20 mm and 40 mm tumours require 0.7 W/g(tumour) and 0.6 W/g(tumour), respectively, whereas smaller tumours require large amounts of heat, e.g. 5 mm and 1 mm tumours require 5.1 W/g(tumour) and 105 W/g(tumour), respectively.Integrating the presently available technologies, including high-quality magnetic nanoparticles (1000 W/g(material)) and effective drug delivery systems (1-2 mg(material)/g(tumour)), treatment of a 10 mm tumour seems possible. Since treatment of smaller tumours less than 5 mm require substantial heat dose, researchers involved in IHCT should target cancer nodules of 10 mm or more, and develop a heat delivery system providing a minimum of 1.7 W/g(tumour).

Purpose of the study: Tight glycemic control is important for the prevention of microvascular complications in diabetic patients. We examined the reliability of using blood glucose levels measured at various time-points relative to a meal as an index of glycemic control in Japanese diabetic outpatients. Basic procedures followed: We examined the correlation between the fasting blood glucose (FBG) level; the one-hour (1-h), two-hour (2-h), and three-hour (3-h) post breakfast blood glucose (PBBG) levels, the 1 h, 2 h, and 3 h post lunch blood glucose (PLBG) levels and the hemoglobin A1c (HbA1c) levels in Japanese diabetic outpatients. A total of 11451 patient-visits to the Marunouchi Hospital between January 2002 and December 2002 were included in the study. The main findings: The blood glucose levels measured at all of the above time-points were significantly correlated with the HbA1c level. As calculated using local polynomial regression fitting, the FPG, 1-h, 2-h, and 3-h PBBG levels that corresponded to an HbA1c level of 6.5% were 132 mg/dL, 174 mg/dL, 170 mg/dL, and 143 mg/dL, respectively. The FPG and 2-h PBBG levels exhibited a good sensitivity and specificity for predicting a glycemic control corresponding to an HbA1c

We have previously demonstrated tumor-specific alpha1,2fucosylation, which is associated with resistance of tumor cells to anticancer treatment in human colorectal tumor tissues. By using the YB-2 monoclonal antibody, the resulting products have been identified as Y, Le(b), and H type 2 antigens in colorectal tumor tissues.Immunohistochemical analyses of colorectal cancer tissues (74 specimens) were performed with a newly established mouse monoclonal antibody, YB-3 specifically recognizing H disaccharide (Fucalpha1,2Galbeta) structures, and anti-A, anti-B, YB-2, and anti-sialyl Lewis X (SLX) antibodies, together with the analyses of glycosyltransferases involved in the synthesis of ABH antigens in the same tissues.The YB-3 antibody enabled us to detect colorectal tumors, particularly tumors in the distal large intestine and the rectum, with high sensitivity (74.3%) and specificity (100%). From immunohistochemical and enzymatic analyses of colorectal tissues, we found that once alpha1,2fucosylation had proceeded in tumor tissues, blood group A or B antigen was also synthesized in approximately half of the tissues of A or B blood type, but not in their normal tissues. A correlation of survival rate with immunostaining of tissues was found only by YB-3 antibody and not by anti-A, anti-B, or anti-SLX antibody.As a predictor of postoperative prognosis of patients with colorectal cancer, immunodetection of alpha1,2fucosylated antigens with the YB-3 antibody seemed to be superior to blood groups A, B, or SLX antigen in colorectal tumor tissues.

No previous reports have focused on surgical treatments and risk factors of umbilical hernia alone in peritoneal dialysis (PD) patients. Herein, we evaluated the treatments and risk factors. A total of 411 PD patients were enrolled. Of the 15 patients with umbilical hernia (3.6%), six underwent hernioplasty. There was no recurrence in five patients treated with tension-free hernioplasty. The mean PD vintage after onset of hernia in the hernioplasty group tended to be longer than that in the non-hernioplasty group. An incarcerated hernia occurred in one non-hernioplasty patient. Although the incidence was significantly higher among women (P = 0.02), female sex was not a risk factor for umbilical hernia (P = 0.08). Our findings suggest that umbilical hernias should be repaired for continuing PD. Furthermore, there were no significant risk factors for umbilical hernia in PD patients. Future studies with larger sample groups are required to elucidate these risk factors.

Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis. The mortality rate for EPS has been high, primarily due to complications related to bowel obstruction. However, recent advances in clinical research have established the pathogenesis, the disease course, and a treatment strategy. Currently, there is consensus on therapy; however, treatment with corticosteroids and tamoxifen should be administered in a timely manner. The final therapeutic option for EPS is surgical enterolysis (adhesiolysis). Moreover, a biocompatible peritoneal dialysis solution has become available for patients worldwide, which may further reduce peritoneal deterioration and EPS risk. These activities have promoted a better understanding of and have prompted countermeasures against EPS. EPS is no longer considered a fatal complication.

The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E(1) (vasodilator and hepatoprotective effect; 500 microg/day) and thromboxane A(2) synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin >10 mg/dl and ascites >1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome.

BACKGROUND Serum α1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries α(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains. METHODS Serum AGP levels in patients with various types of malignancies (n = 214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody. RESULTS A significant difference (P < 0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods. CONCLUSIONS Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis. Cancer 2004. © 2004 American Cancer Society.

Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics.Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features.Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P0.05), vessel-cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 μm; P0.001), and microvessel density was lower (6.8 ± 1.9 vs 10.8 ± 2.1 vessels/0.4 mm(2); P0.05) in tumor grafts. Drug concentrations in tumor grafts were lower than those in cell xenografts (3.3 ± 1.2 vs 6.0±0.2 μg/mL; P = 0.003), and the differences were correlated with the histological differences.Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.

Background When the kidney from a living donor with a double inferior vena cava (IVC) is harvested for renal transplantation, the short length of the renal vein may eventually create a technical problem for graft implantation. Herein, we have reported a rare case of renal vein extension using an autologous renal vein in a living donor with a double IVC. Case Report A 70-year-old man with end-stage renal disease owing to autosomal-dominant polycystic kidney disease underwent a living donor kidney graft from his wife who had a double IVC. Because of the enlarged kidneys, the patient underwent a bilateral native nephrectomy with concomitant renal transplantation to create space in the pelvis. At nephrectomy, the recipient's renal vein was used to extend the donor renal vein. On the back table, the vein graft was sutured to the donor renal vein, permitting a 3.0-cm extension. Results The transplantation was performed safely without any complications; the recipient's renal function and blood flow were excellent after the operation. Conclusion This case illustrated that an autologous renal vein graft is a preferable option to extend of short donor renal vein for recipients who require a simultaneous native nephrectomy.

Aspirin significantly increases the risk of peptic ulcer. Since it remains to be determined whether gastroprotective agents should be used routinely in patients without risk factors who are taking aspirin, more risk factors for aspirin-related peptic ulcer should be detected. In the present study was investigated the effects of aspirin on upper gastrointestinal ulcer and potent risk factor for peptic ulcer associated with aspirin in a case-control study.It was identified 137 newly diagnosed gastroduodenal ulcer cases from endoscopic examinees in the Gunma Prefectural Cardiovascular Center. Two controls per case were selected according to sex and age, and we determined 274 controls. It was calculated OR and 95% CI of peptic ulcer for serum triglycerides.The use of low-dose aspirin without gastroprotective agents was found to be associated with the risk of peptic ulcer. High serum triglycerides were associated only with aspirin-related peptic ulcer. In contrast, no elevated OR of peptic ulcer was shown in cases without aspirin.The present study results suggest that hypertriglycerides might be one of the risk factors for peptic ulcer caused by aspirin. These findings indicate that gastroprotective therapy should be considered for preventing peptic ulcer associated with low-dose aspirin in patients with hypertriglyceridemia.

Several trials have demonstrated beneficial effects of statins in some biological activities that go beyond lipid lowering, suggesting that statins might have other therapeutic benefits. However, it remains to be determined whether statin use is correlated with upper gastrointestinal diseases. We investigated the effects of statin therapy on gastroduodenal ulcers or reflux esophagitis (RE) in a case-control study.We identified 120 newly diagnosed gastroduodenal ulcer cases and 146 RE cases from endoscopic examinees in the Gunma Prefectural Cardiovascular Center. Two controls per case were respectively selected according to sex and age and we determined 240 and 292 controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) of peptic ulcer and RE for statin use.Statin use was not associated with the risk of peptic ulcer (OR 1.2; 95% CI 0.7-2.1), and no elevated OR of RE was shown (OR 0.8; 95%CI 0.5-1.4). Ever use of hydrophilic statins, or lipophilic statins was not associated with the risk of peptic ulcer or RE.Our results suggest that statin use might not be associated with peptic ulcer or RE. These findings indicate that statin therapy might be safe for patients with upper gastrointestinal disease.

Magnetic nanoparticles have recently been widely applied in the bio-medical field. Responding to the demand for a simple and sensitive magnetic assay system for bio-liquid samples, we employed a general-purpose superconducting quantum interference device (SQUID) magnetometer. Strips of filter paper were used as a liquid-specimen sample holder possessing a very small magnetic background signal. An aqueous solution of superparamagnetic iron-oxide nanoparticles (Resovist) was dropped in a tiny blot-like spot in the middle of the filter paper and the magnetization was measured. Magnetic moments of a dilution series of Resovist solutions versus the number of particles provided a linear graph, revealing that the magnetic moment per Resovist particle was 8.25 x 10(-17) emu. 1 x 10(5) cancer cells were incubated with Resovist, and the number of Resovist particles attached to the cell surface and surrounding a living cell was calculated to be 1.02 +/- 0.14 x 10(7) particles/cell. Our system using a commercial SQUID magnetometer should be more than enough to determine the number of magnetic nanoparticles biologically reacting with living cells, contributing to the application of magneto nanomaterials to the life-science field.

A 24-year-old female complaining of diarrhea and back pain was admitted to hospital where a tumor of the pancreatic head was revealed on a computed tomography (CT) scan. Abdominal ultrasonography, CT and celiac angiography revealed a hypervascular lesion on the pancreas. An endocrine tumor, particularly a somatostatinoma, was suspected and hormone levels in the blood were examined. Serum hormone levels were normal, so FDG-PET was performed. An abnormally high accumulation of FDG was detected on the FDG-PET image at the head of the pancreas, and the SUV of the lesion was 3.2, so the mass was considered to be malignant on FDG-PET. Pylorus-preserving pancreatoduodenectomy was performed with a preoperative diagnosis of malignant endocrine tumor. The resected specimen revealed a massive, yellowish-white tumor of the pancreas head measuring 50x 45x38mm. Histologically, the tumor was a malignant islet-cell tumor, and immunohistochemically the tumor stained with an anti-somatostatin antibody, but not with antibodies against glucagons, insulin or vasoactive intestinal polypeptide. The patient was discharged after the operation and has remained well without recurrence for 5 years. Liver metastatic tumors, however, appeared 6 years after the operation.

Parkinson’s disease is a chronic progressive disease with symptoms of tremors, rigidity, and akinesia. Parkinson’s disease is a major risk factor for postoperative complications and it is difficult to manage patients with Parkinson’s disease after gastrointestinal surgery. This report presents the cases of three patients with Parkinson’s disease who underwent gastrointestinal surgery and had no serious postoperative complications. Antiparkinsonian medications were reduced before surgery and replaced by an intravenous infusion of levodopa until the patients could take oral antiparkinson drugs after surgery to prevent malignant syndrome or exacerbate parkinsonism. Prokinetics were also used for the prevention of paralytic ileus. These cases demonstrate an effective method to administer antiparkinson drugs during perioperative management of patients with Parkinson’s disease and also indicate that sufficient doses of antiparkinson drugs can control the symptoms of parkinsonism and prevent complications in cases of surgery with parkinsonism.

In living donor liver transplantation (LDLT), donor safety has top priority, and donor morbidity should be minimized to zero. However, several corporal problems still remain. The effect of hyperbaric oxygenation treatment (HBO) was evaluated for donor morbidity in LDLT.A total of 14 consecutive donors were studied. The donors into were divided into 2 groups as follows: HBO group (n=7), which started HBO 3 days after operation, and a control group (n=7). Patient's factors, graft volume, liver regeneration rate, liver function tests and postoperative complications ware compared between the 2 groups.There was no significant difference between the groups in whole liver, graft and remnant liver volume. The incidence of wound numbness on POD 28 was 86% (6/7) in the control group and 29% (2/7) in the HBO group (p0.05). Postoperative hospital stay was 14.4 and 14.6 days in the control and HBO group, respectively (p=NS). On POD 14, AST value in the HBO group was significantly lower than in the control group (p0.05). PT% value in the HBO group was significantly higher than in the control group on POD 14 (p0.05). Total bilirubin level in the HBO group was significantly lower than in the control group on POD 14 and 28 (p0.05), and total bile acid value in the HBO group was significantly lower than the control group (p0.05) on POD 14. Albumin level in the HBO group was significantly higher than the control group on POD 7, 10 and 28 (p0.05). Four weeks after the operation, the regeneration rate was significantly higher in the HBO group than in the control group (p0.05).Liver regeneration was promoted by HBO preserving a function in LDLT using left lobe graft. Hyperbaric oxygen therapy seems to be very useful to LDLT.

Fascin, an actin-crosslinking protein, participates in cell motility. Fascin over-expression induces a high potential for invasion and metastasis in various malignancies. The aim of this study was to determine the relationship of fascin expression to clinicopathological findings in patients with extrahepatic bile duct cancer. Furthermore, we investigated the correlation between fascin expression and intracellular adhesion molecular (E-cadherin and beta-catenin).We evaluated the expression of fascin, E-cadherin and beta-catenin by immunohistochemistry in surgical specimens from 26 patients with extrahepatic bile duct cancer.Normal epithelial cells of the bile duct was not immunoreactive for fascin, and cancer cells often show immunoreactivity, which was found more frequently at the invasive tumor fronts than at other tumor areas. The present study demonstrated a statistically significant correlation between fascin expression and gender, tumor status, vascular invasion, and disease stage. We detected that increased immunoreactivity for fascin had tendencies to disrupt membranous immunoreactivity for E-cadherin and beta-catenin.We conclude that fascin expression is correlated with tumor progression. The expression of fascin is frequently detected at the invasive tumor fronts, indicating that invading tumor cells express fascin abundantly. In tumor cells with an over-expression of fascin, E-cadherin and betacatenin expressions often disrupt membranous immunoreactivity.

Pancreatic cancer is an intractable malignancy with the poorest prognosis among digestive tract cancers. It is important when we obtain informed consent (IC) from patients with pancreatic cancer and their families to convey sufficiently that pancreatic cancer is intractable and provide support to help patients maintain a positive attitude toward treatment. Although the efficacy of chemo (radiation) therapy in pancreatic cancer is still unclear, the progress of various clinical trials on postoperative adjuvant therapy centered on gemcitabine hydrochloride, and chemo (radiation) therapy for unresectable tumors has raised expectations in recent years. To enable each individual patient to select the optimal treatment based on his or her personal outlook on life, it is important to obtain IC in good faith through the accurate diagnosis of pancreatic cancer and the use of the latest treatment information.

Glucokinase (Gck) functions as a glucose sensor for insulin secretion, and in mice fed standard chow, haploinsufficiency of beta cell-specific Gck (Gck(+/-)) causes impaired insulin secretion to glucose, although the animals have a normal beta cell mass. When fed a high-fat (HF) diet, wild-type mice showed marked beta cell hyperplasia, whereas Gck(+/-) mice demonstrated decreased beta cell replication and insufficient beta cell hyperplasia despite showing a similar degree of insulin resistance. DNA chip analysis revealed decreased insulin receptor substrate 2 (Irs2) expression in HF diet-fed Gck(+/-) mouse islets compared with wild-type islets. Western blot analyses confirmed upregulated Irs2 expression in the islets of HF diet-fed wild-type mice compared with those fed standard chow and reduced expression in HF diet-fed Gck(+/-) mice compared with those of HF diet-fed wild-type mice. HF diet-fed Irs2(+/-) mice failed to show a sufficient increase in beta cell mass, and overexpression of Irs2 in beta cells of HF diet-fed Gck(+/-) mice partially prevented diabetes by increasing beta cell mass. These results suggest that Gck and Irs2 are critical requirements for beta cell hyperplasia to occur in response to HF diet-induced insulin resistance.

The authors report herein a case of primary sclerosing cholangitis localized to the hepatic hilum which occurred in a 67-year-old male. The direct cholangiography revealed bile duct stenosis from the common hepatic duct to bilateral hepatic ducts. We could not confirm bile duct malignancy, however, hilar cholangiocarcinoma was most suspicious. We performed right trisegmentectomy of the liver with caudate lobectomy and lymph node dissection 3 weeks after right portal embolization. Pathological findings confirmed localized primary sclerosing cholangitis. Surgical resection of the affected bile duct is most effective in localized primary sclerosing cholangitis, because the prognosis of the disease is poor and secondary carcinogenesis in primary sclerosing cholangitis has high incidence.

Combined hepatocellular and cholangiocellular carcinomas are rare. Moreover, double cancer cases of hepatocellular carcinoma and cholangiocellular carcinoma are very rare. This report describes a patient with double cancer. A correct clinical diagnosis was made with successful resection, and cutaneous metastases occurred near the exit site of an abdominal drain after the resection of the tumor. The patient, a 66-year-old man with chronic hepatitis C, was admitted to our hospital because he was suspected of having primary liver cancer. Two liver masses in the anteroinferior segment were detected by using angiography, computed tomography during angiography, and computed tomography during arterioportography. These clinical findings indicated that the tumor in the right lobe was hepatocellular carcinoma. A resection of the S5 subsegmentectomy was performed. One mass was diagnosed histologically as hepatocellular carcinoma, and the other mass was diagnosed as cholangiocellular carcinoma. One year after the operation, the patient palpated a hard subcutaneous nodule 4.0 cm in diameter in the right lower abdominal wall. A subcutaneous tumor was excised, and a histological examination revealed moderately differentiated hepatocellular carcinoma. The patient is currently doing well without further recurrence of hepatocellular carcinoma or cholangiocellular carcinoma, 18 months after subsegmentectomy and six months after excision of the subcutaneous tumor.