[Case of Resected Retroperitoneal Dedifferentiated Liposarcoma Extending to the Posterior Mediastinum].

A 71-year-old woman visited our hospital for the examination and treatment of retroperitoneal tumor. CT showed a retroperitoneal tumor extending to the posterior mediastinum; the tumor pressed the IVC and widely abutted the aorta. On MRI, the tumor showed low intensity on T1WI and high intensity on T2WI and DWI. However, the tumor did not show signal reduction on an ADC map. PET-CT showed high accumulation at the tumor. The patient was diagnosed with sarcoma arising from the retroperitoneum. The tumor located on a part of the diaphragm was resected. Histological examination revealed spindle cells with atypical nuclear and multinuclear cells. There were no lesions of well-differentiated liposarcoma. Both CDK4 and MDM2 tested positive on immunohistological staining. Histopathologically, the tumor was diagnosed as dedifferentiated liposarcoma without any well-differentiated liposarcoma component. The postoperative course was uneventful, and she was discharged on the 13th day after surgery. Two months after surgery, no recurrence has been detected.

Cholecystohepatic duct detected during laparoscopic cholecystectomy: a case report.

BACKGROUND: The cholecystohepatic duct is a rare form of an aberrant hepatic duct that connects to the gallbladder. Although cholecystohepatic duct is reported to be a very rare anomaly, injury of cholecystohepatic duct during cholecystectomy may result in serious complications. Herein, we present a case of cholecystohepatic duct in the ventral branch of the right posterior inferior segmental bile duct detected during laparoscopic cholecystectomy. CASE PRESENTATION: A 77-year-old woman with cholecystolithiasis had been referred to our hospital for surgery. Drip infusion cholecystocholangiography-computed tomography revealed a bile duct branch without communication between the intra- and extrabiliary systems, although the existence of this aberrant hepatic duct was not suspected preoperatively. A 4-port laparoscopic cholecystectomy was performed. After critical view of safety was confirmed, the cystic artery and duct were divided after double clipping. During antegrade mobilization of the gallbladder from the gallbladder bed, a thin, white cord-like material connecting the gallbladder neck and bed was detected. After clipping and dividing it, a cholecystohepatic duct injury was recognized through rechecking the results of the preoperative examinations. Biliary reconstruction was considered unnecessary because of the lesion's small drainage area. The postoperative course was uneventful, and an enhanced computed tomography performed 6 months after the surgery revealed a dilation in the ventral branch of the right posterior inferior segmental bile duct. The patient's liver function remained normal, and she had no symptoms of cholangitis 42 months after the surgery. CONCLUSIONS: Although cholecystohepatic duct is a rare anomaly compared to other aberrant hepatic ducts, surgeons performing cholecystectomy should always keep its existence in mind to avoid serious postoperative complications. Ideally, preoperative detection of cholecystohepatic duct is preferable, but even if it is detected during surgery, the appropriate management according to the drainage area is also important.

[Two Cases of Complete Response to Trastuzumab Combined with Chemotherapy for Recurrence of HER2-Positive Gastric Cancer].

Case 1: A 67-year-old male underwent distal gastrectomy for advanced gastric cancer. Postoperative histopathological examination indicated pT2a, pN2, M0, pStage ⅢA. He received 4 courses of TS-1 with paclitaxel chemotherapy and TS-1 chemotherapy for 2 years. Three years and 5 months after surgery, computed tomography suggested lymph node metastasis of the mediastinum, so TS-1 with cisplatin(CDDP)therapy was administered. Five years and 10 months after surgery, recurrence occurred and docetaxel and CPT-11 were administered with no response. Since HER2 was overexpressed in the primary tumor, he was treated with capecitabine, CDDP, and trastuzumab(XPT)therapy. After 1 year and 6 months, the patient was considered to have achieved a complete response(CR), and after further trastuzumab therapy for half a year, CR was maintained for 12 years and 3 months after surgery. Case 2: A 59-year-old female underwent total gastrectomy for advanced gastric cancer. Postoperative histopathological examination indicated pT3, pN3a, M0, pStageⅢB. She received TS-1 chemotherapy for 1 year and 8 months. Computed tomography suggested paraaortic lymph node metastasis, and XPT therapy was administered. The patients responded well, and alternate administration of XPT and capecitabine and docetaxel(XT) was performed. Three years and 5 months after surgery, recurrence of lymphadenopathy occurred and intensity-modulated radiation therapy in addition to XPT/XT alternate therapy was introduced, leading to a CR 5 years and 8months after surgery. XT therapy was continued afterward, and CR was maintained for 9 years and 2 months after surgery.

[A Resected Case of UR-LA Pancreatic Tail Cancer with Aortic Invasion after Chemoradiotherapy].

A 70-year-old male was referred to our hospital because of weight loss and epigastric discomfort. CT showed an irregularshaped, low-density tumor, 12 cm in diameter in the tail of the pancreas. This tumor widely invaded to the left kidney and to the anterior and left lateral sides of the aorta in spite of no involvement of celiac and superior mesenteric arteries. Moreover, it closely contacted with the stomach and the spleen. EUS-fine-needle aspiration biopsy of the tumor detected adenocarcinoma. Thus, he was diagnosed with UR-LA pancreatic cancer with aortic invasion. He received combination chemotherapy(S-1 plus gemcitabine[GEM])and 50.4 Gy 3-dimensional conformal radiation therapy, but this therapy had no expected effect. We changed the regimen to GEM plus nab-PTX. After 1 course of changed regimen, the tumor ruptured into the stomach and endoscopic debridement of the necrotic tissue was performed. Twenty-six days later, We performed distal pancreatectomy with splenectomy, total gastrectomy, left nephrectomy, left adrenalectomy, and segmental resection of the colon. The tumor was detached from the aorta as much as possible. The final diagnosis was pT3N0M0, pStage II A. Fifty-nine days after operation, we restarted GEM plus nab-PTX therapy. However, a cerebral infarction suddenly occurred, and we discontinued the chemotherapy. Five months after the operation, he died of cancerous peritonitis.

[A Case of Small Intestinal Neuroendocrine Tumor Detected One Year after Resection of Liver Metastasis].

A 49-year-old woman received a detailed examination for a myoma uteri, and a hepatic tumor was detected incidentally. A CT scan showed a tumor 6 cm in diameter in the posterior segment, which was irregularly enhanced. The tumor showed a low signal intensity on T1WI MRI and a slightly high intensity with high-density spots on T2WI. The tumor showed a low signal intensity in the hepatobiliary phase of the EOB-enhanced MRI. Percutaneous liver biopsy proved that this tumor was a grade 1 neuroendocrine tumor(NET G1). We examined her whole body in detail but found no primary lesions. Therefore, we made a diagnosis of primary hepatic NET or hepatic metastasis of an unknown origin and performed right hepatectomy. A year after the operation, a tumor was found in the jejunum. We made a diagnosis of NET by using endoscopic biopsy and performed partial intestinal resection. Histological findings showed NET G2(Ki-67 labeling index: 3.5%), which had venous invasion and one lymph node metastasis, suggesting that the jejunum was a primary lesion of NET. Three years and 2 months after the first operation, multiple liver metastases were found, and bland TAE was performed three times. Four years and 6 months after the first operation, we started sustained-release somatostatin analogues for tumor progression. She is still alive 5 years and 6 months after the first operation.

Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).

Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis.

[A Case of Primary Peritoneal Cancer Successfully Treated with Debulking Surgery and Postoperative Chemotherapy].

A 52-year-old woman with abdominal pain and a feeling of incomplete evacuation visited a local clinic. Enlargement of the right ovary was detected, and the patient was referred to the gynecological department of our hospital. CT and MRI revealed a round-shaped mass, 8 cm in diameter, with cystic and solid components in the Douglas pouch. The patient underwent a laparotomy under the diagnosis of ovarian cancer. Intraoperatively, both the ovaries appeared normal and the tumor strongly adhered to the rectum and uterus. An exploratory laparotomy was performed; the tumor was identified as unresectable, and the patient was referred to our department after the surgery. PET-CT revealed nodules in the liver and peritoneum, in addition to the main tumor. Gastrointestinal endoscopy and immunohistochemical examination of a needle biopsy of the main tumor did not lead to the identification of the primary lesion. Thus, debulking surgery was performed to alleviate the patient's complaints. Histologically, the tumor was diagnosed as a primary peritoneal clear cell carcinoma. One month after surgery, multiple liver metastases and swelling of the peritoneal lymph nodes occurred. Six courses of dose-dense TC therapy were administered, and the patient achieved a complete response. At 8 months after surgery, the patient is still alive without tumor recurrence.

Immunological aspects in late phase of living donor liver transplant patients: usefulness of monitoring peripheral blood CD4+ adenosine triphosphate activity.

AIM: To evaluate whether the combination of the peripheral blood CD4+ adenosine triphosphate activity (ATP) assay (ImmuKnow assay: IMK assay) and cytochrome P450 3A5 (CYP3A5) genotype assay is useful for monitoring of immunological aspects in the patient followup of more than one year after living donor liver transplantation (LDLT). METHODS: Forty-nine patients, who underwent LDLT more than one year ago, were randomly screened by using IMK assay from January 2010 to December 2011, and the complete medical records of each patient were obtained. The CYP3A5 genotypes were examined in thirty-nine patients of them. RESULTS: The mean ATP level of the IMK assay was significantly lower in the patients with infection including recurrence of hepatitis C (HCV) (n = 10) than in those without infection (n = 39): 185 versus 350 ng/mL (P < 0.001), while it was significantly higher in the patients with rejection (n = 4) than in those without rejection (n = 45): 663 versus 306 ng/mL (P < 0.001). The IMK assay showed favorable sensitivity/specificity for infection (0.909/0.842) as well as acute rejection (1.0/0.911). CYP3A5 genotypes in both recipient and donor did not affect incidence of infectious complications. CONCLUSIONS: In the late phase of LDLT patients, the IMK assay is very useful for monitoring immunological aspects including bacterial infection, recurrence of HCV, and rejection.

An approach to the intra-thoracic inferior vena cava through the abdominal cavity preparing for total hepatic vascular exclusion by sagittal diaphragmotomy.

BACKGROUND/AIMS: For resection of advanced liver tumors with tumor thrombus/invasion extending into the intra-thoracic inferior vena cava (IVC) above the diaphragm as well as huge liver tumors located at the root of hepatic vein, an appropriate approach to the intra-thoracic IVC through the abdominal cavity is the key to control the intraoperative massive bleeding. SURGICAL TECHNIQUE: The pericardium and diaphragm are separated by using fingers without injury of the pericardium. From just below the xiphoid process to the IVC, the diaphragm is vertically dissected without cutting the pericardium and doing median sternotomy. Then the intra-thoracic IVC is exposed easily and encircled with an umbilical tape. RESULTS: This technique was applied in four patients (hepatocellular carcinoma: n = 3, cholangiocellular carcinoma: n = 1). The mean patient's age was 69 (59-81) year old, and three were male. The median duration of surgery and blood loss was 490 min and 3600 mL, respectively. The median peaked aspartate aminotransferase and total bilirubin was 428 IU/mL and 2.75 mg/dL, respectively. The median duration of hospital stay was 22 days. CONCLUSIONS: This approach to intra-thoracic IVC through the abdominal cavity is very beneficial and helpful for many liver surgeons.

Combination assays for evaluation of immune function and CYP3A5 genotype to identify the risk of infectious complications and mortality in living donor liver transplant patients.

BACKGROUND: The aim of this study is to evaluate whether the combination of the ImmuKnow assay (IMK) and cytochrome P450 3A5 (CYP3A5) genotype assay is useful for identifying the risk of morbidity and mortality in living donor liver transplantation (LDLT) patients, and also to investigate the optimal cutoff value of IMK level of immune status. MATERIAL AND METHODS: Sixty six LDLT patients, who were randomly screened by using IMK between March 2002 and June 2011, were divided into 2 groups: patients in whom at least 1 IMK value was <175 ng/mL (Group A, n=16) and patients in whom all IMK values were >175 ng/mL (Group B, n=50). Both donors and recipients were evaluated for the CYP3A5 genotype. RESULTS: The frequencies of cytomegalovirus and bacterial infection in Group A were significantly higher than those in Group B (P<0.001). The short term mortality was 4 (25.0%) in Group A and none in Group B, and the IMK level in all four cases became <100 ng/mL at least one time before death. The rate of CYP3A5*1 allele (expressors) among recipients was significantly higher in Group A than in Group B (63.6% vs. 22.2%, P=0.0147). The rates of CMV infection and bacterial infection, and the IMK levels was significantly higher in recipients with expressors (p=0.0216, p=0.0332, and p=0.0433, respectively). CONCLUSIONS: The combination of the IMK and CYP3A5 genotype assay is useful for monitoring immune status after LDLT, and the IMK level <100 ng/ml might be the critical level to make a recovery from the severe immunesupressive condition.

The novel guanylhydrazone CPSI-2364 ameliorates ischemia reperfusion injury after experimental small bowel transplantation.

BACKGROUND: Resident macrophages within the tunica muscularis are known to play a crucial role in initiating severe inflammation in response to ischemia reperfusion injury after intestinal transplantation contributing to graft dysmotility, bacterial translocation, and possibly, acute rejection. The p38 mitogen-activated protein kinase is a key player in the signaling of proinflammatory cytokine synthesis in macrophages. Therefore, we investigated the effects of CPSI-2364, an apparent macrophage-specific inhibitor of the p38 mitogen-activated protein kinase pathway in an isogenic intestinal rat transplantation model. METHODS: Recipient and donor animals were treated perioperatively with CPSI-2364 (1 mg/kg, intravenously) or vehicle solution. Nontransplanted animals served as control. Animals were killed 30 min, 3 hr, and 18 hr after reperfusion. RESULTS: CPSI-2364 treatment resulted in significantly less leukocyte infiltration and significantly improved graft motor function (18 hr). Messenger RNA expression of proinflammatory cytokines (interleukin 6) and kinetic active mediators (NO) was reduced by CPSI-2364 in the early phase after transplantation. Histologic evaluation revealed the protective effects of CPSI-2364 treatment by a significantly less destruction of mucosal integrity at all time points. Perioperative treatment with CPSI-2364 improves graft motor function through impaired inflammatory responses to ischemia reperfusion injury by inhibition of proinflammatory cytokines and suppression of nitric oxide production in macrophages. CONCLUSIONS: CPSI-2364 presents as a promising complementary pharmacological approach preventing postoperative dysmotility for clinical intestinal transplantation.

A natural tetrahydropyrimidine, ectoine, ameliorates ischemia reperfusion injury after intestinal transplantation in rats.

BACKGROUND/AIMS: Ischemia reperfusion (I/R) injury after small bowel transplantation leads to inflammatory reactions and loss of structural integrity with subsequent graft contractile dysfunction in the early postoperative phase. The natural tetrahydropyrimidine ectoine (1-,4-,5-,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid; THP) protects the ileal mucosa and muscularis against effects of I/R injury in an experimental model of isolated graft reperfusion. The effects of THP treatment were evaluated in an established experimental intestinal transplant model. METHODS: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (6 h cold ischemia time). Perioperative THP treatment (intraluminal/intravascular) groups were compared to vehicle-treated animals (after 3 and 24 h) and non-transplanted controls (n = 5/group). Park's score defined the effects of I/R injury. The infiltration of neutrophils, monocytes and macrophages, mRNA expression of IL-6 and TNF-α, serum levels of IL-6 and NO and smooth muscle contractility were evaluated. RESULTS: Improved graft outcome after intraluminal and intravascular THP treatment was defined by considerably ameliorated neutrophil infiltration and less histological signs of I/R injury (p ≤ 0.05). In the presence of THP, mRNA expression of IL-6 and TNF-α and IL-6 and NO serum levels were reduced and smooth muscle function was improved. CONCLUSION: THP treatment offers protection against the effects of I/R injury in intestinal transplantation in vivo, however, only as supplementary treatment option.

Orthotopic small bowel transplantation in rats.

Small bowel transplantation has become an accepted clinical option for patients with short gut syndrome and failure of parenteral nutrition (irreversible intestinal failure). In specialized centers improved operative and managing strategies have led to excellent short- and intermediate term patient and graft survival while providing high quality of life (1,3). Unlike in the more common transplantation of other solid organs (i.e. heart, liver) many underlying mechanisms of graft function and immunologic alterations induced by intestinal transplantation are not entirely known(6,7). Episodes of acute rejection, sepsis and chronic graft failure are the main obstacles still contributing to less favorable long term outcome and hindering a more widespread employment of the procedure despite a growing number of patients on home parenteral nutrition who would potentially benefit from such a transplant. The small intestine contains a large number of passenger leucocytes commonly referred to as part of the gut associated lymphoid system (GALT) this being part of the reason for the high immunogenity of the intestinal graft. The presence and close proximity of many commensals and pathogens in the gut explains the severity of sepsis episodes once graft mucosal integrity is compromised (for example by rejection). To advance the field of intestinal- and multiorgan transplantation more data generated from reliable and feasible animal models is needed. The model provided herein combines both reliability and feasibility once established in a standardized manner and can provide valuable insight in the underlying complex molecular, cellular and functional mechanisms that are triggered by intestinal transplantation. We have successfully used and refined the described procedure over more than 5 years in our laboratory (8-11). The JoVE video-based format is especially useful to demonstrate the complex procedure and avoid initial pitfalls for groups planning to establish an orthotopic rodent model investigating intestinal transplantation.

Dual cytoprotective effects of splenectomy for small-for-size liver transplantation in rats.

The problems associated with small-for-size liver grafts (ie, high mortality rates, postoperative complications, and acute rejection) remain critical issues in partial orthotopic liver transplantation (OLT). In association with partial OLT, splenectomy (SP) is a procedure used to reduce the portal pressure. However, the precise effects of SP on partial OLT have been unclear. In this study, using small-for-size liver grafts in rats, we examined the cytoprotective effects of SP on OLT. Liver grafts were assigned to 2 groups: a control group (OLT alone) and an SP group (OLT after SP). SP significantly increased animal survival and decreased liver damage. SP exerted the following cytoprotective effects: (1) it improved hepatic microcirculation and prevented increases in the portal pressure after OLT, (2) it suppressed the hepatic infiltration of neutrophils and macrophages through the direct elimination of splenic inflammatory cells before OLT, (3) it decreased the hepatic expression of tumor necrosis factor α and interleukin-6, (4) it attenuated sinusoidal endothelial injury, (5) it decreased plasma endothelin 1 levels and increased hepatic heme oxygenase 1 expression, (6) it suppressed hepatocellular apoptosis through the down-regulation of hepatic caspase-3 and caspase-8 activity, and (7) it increased hepatic regeneration. In conclusion, SP for small-for-size grafts exerts dual cytoprotective effects by preventing excessive portal vein hepatic inflow and eliminating splenic inflammatory cell recruitment into the liver; this in turn inhibits hepatocellular apoptosis and improves liver regeneration.

Research of masticatory function using hemiplegia simulator equipment.

BACKGROUND AND OBJECTIVE: Hemiplegic patients often exhibit a characteristic condition called Wernicke-Mann contracture. Therefore, the occlusal pattern in hemiplegic patients is considered to be adapted to stress because of this characteristic limb position. We created a sham Wernicke-Mann contracture in healthy individuals using hemiplegia simulator equipment and compared the functional occlusion in this position with that in the normal state to evaluate dynamic adaptive responses. METHODS: Wernicke-Mann contracture was simulated using a device to create sham hemiplegia (Manabi-tai, Hemiplegia Experiencing Set; Tokushu-iryo, Inc.). In addition to the measurement of the occlusal force using Dental Prescale(®) and Occluzer(®), the occlusion was evaluated using an electromyogram and stabilometer. RESULTS: There was a significant difference in the occlusal force between the normal state and during simulated hemiplegia. The surface electromyo-potential of the masseter muscle showed significantly higher values during simulated hemiplegia. It is significantly higher during simulated hemiplegia than in the normal state on the paralysed side, but not for the normal state on the non-paralysed side. The position and velocity vectors changed in the antero-posterior direction in the normal state but in the lateral direction during simulated hemiplegia. CONCLUSIONS: The hemiplegia simulator equipment is useful for research on hemiplegia, and that the occlusal balance is disturbed in the posture characteristic of hemiplegia.

Combination therapy of tacrolimus and infliximab reduces inflammatory response and dysmotility in experimental small bowel transplantation in rats.

BACKGROUND: Intestinal transplantation initiates a functionally relevant inflammatory response by activation of resident macrophages within the muscularis associated with dysmotility. Infliximab is used successfully as a potent anti-inflammatory agent for the treatment of chronic inflammatory bowel diseases and as rescue therapy in acute steroid-resistant rejection in selected settings in clinical small bowel transplantation. We hypothesize that additional perioperative treatment with infliximab diminishes initiation of the inflammatory cascade and improves motility in small bowel grafts using a standard tacrolimus immunosuppressive protocol. METHODS: Orthotopic intestinal transplantation was performed in rats. In two treatment groups (24/168 hr), infliximab was administered intravenously directly after reperfusion and tacrolimus was injected intramuscularly after transplantation and once a day. Two other treatment groups (24/168 hr) received standard immunosuppressive therapy with tacrolimus. Isogenic and allogenic transplanted vehicle-treated animals (24/168 hr) and native gut served as control. RESULTS: Infliximab-treated grafts exhibited significantly less leukocyte infiltration at 24/168 hr after transplantation and at 168 hr significantly less apoptosis in the tunica muscularis compared with tacrolimus monotherapy. Additional infliximab treatment resulted in increased smooth muscle contractility (30%) after 24 hr compared with tacrolimus control. CONCLUSIONS: Dysmotility of transplanted small bowel results from reperfusion injury and acute rejection. Additional perioperative treatment with infliximab reduces early unspecific inflammatory responses and complements immunosuppressive therapy with tacrolimus.

Human equilibrative nucleoside transporter 1 expression is a strong independent prognostic factor in UICC T3-T4 pancreatic cancer patients treated with preoperative gemcitabine-based chemoradiotherapy.

BACKGROUND/PURPOSE: We aimed to determine the relationship between the intratumoral expression of human equilibrative nucleoside transporter (hENT1), the main gemcitabine transporter into cells, and the outcome of gemcitabine-based chemoradiotherapy (Gem-CRT) in patients with International Union Against Cancer (UICC) T3-T4 pancreatic adenocarcinoma. METHODS: The expressions of hENT1, thymidylate synthase (TS), and dihydropyrimidine dehydrogenase were immunohistochemically analyzed using the resected specimens from 55 patients (T3, 38 and T4, 17) who had received curative-intent resection after Gem-CRT. RESULTS: The status of hENT1 expression (positive in 39 and negative in 16) was significantly associated with "clinical efficacy" (defined as more than 50% reduction of the serum carbohydrate antigen [CA] 19-9 level with stable disease [SD] or partial response [PR] according to the Response Evaluation Criteria in Solid Tumors [RECIST]) for Gem-CRT. The 1- and 3-year overall survival (OS) rates were significantly higher in the positive hENT1 expression group (82.9, 39.5%) than in the negative expression group (42.9, 14.3%) (p = 0.0037). According to combination analysis of hENT1 and TS expressions, the 1- and 3-year OS rates were significantly higher in the positive-low combination (89.1, 51.0%) group than in the negative-high group (66.7, 0%) (p = 0.023). Multivariate analysis revealed that positive hENT1 expression and R0 resection were significant prognostic factors for OS. CONCLUSIONS: The hENT1 expression in pancreatic adenocarcinoma strongly influences the outcome of preoperative Gem-CRT treatment. This biomarker could become a useful predictor of therapeutic effect for gemcitabine-based therapy in pancreatic cancer patients.

Pancreaticoduodenectomy with resection of the splenic artery and splenectomy for pancreatic double cancers after total gastrectomy. Preservation of the pancreatic function via the blood supply from the posterior epiploic artery: report of a case.

The patient was a 56-year-old man who had previously undergone a total gastrectomy without splenectomy, and was diagnosed with pancreatic head and body cancers and primary solitary lung cancer. The pancreas body tumor invaded the origin of the splenic artery, and if the origin of the splenic artery were resected there would be no blood flow to the pancreas tail, resulting in a need for total pancreatectomy. However, we focused on the posterior epiploic artery (PEA), which is a less well known blood supply from the mesocolon to pancreatic body and tail, and planned to preserve the pancreatic tail as long as the resected margin of the pancreas was not malignant, considering his limited life expectancy. We performed a pancreaticoduodenectomy with resection of the origin of the splenic artery and splenectomy, preserving the pancreatic tail and PEA. The patient has been free from insulin therapy for blood sugar control, and has been well for 10 months after the surgery.

Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

Chemopreventive anti-cancer agent acyclic retinoid suppresses allogeneic immune responses in rats.

Acyclic retinoid NIK-333 (ACR) is a chemopreventive agent that acts by suppressing the recurrence of hepatocellular carcinoma (HCC) following initial treatment and is now being employed in clinical trials. The chemopreventive effects of ACR have been analyzed from various aspects, and it is well known that some retinoic acid (RA) derivatives affect host immunity. The objective of this study is to investigate the effects of ACR on host immunity. The results demonstrated that ACR prolonged heart and liver graft and recipient survival in rat allogeneic organ transplantation. The immunosuppressive effect of ACR administered at 100mg/kg/day was almost equivalent to that of CsA administered at 1mg/kg/day in vivo. In the mixed lymphocyte reaction (MLR), ACR suppressed lymphocyte proliferation non-specifically. Gene expression analysis of splenic lymphocytes from ACR-treated recipient rats revealed no distinct change in Interleukin (IL)-2 and increases in Interferon (IFN)-gamma. In conclusion, ACR possesses immunosuppressive potential in vivo and is a promising chemopreventive drug for long term use against HCC.