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Among portosystemic shunts, splenorenal shunts can cause increased portal pressure, which in turn can bring about hyperammonemia, resulting in hepatic encephalopathy. In recent years, it has been reported that oxaliplatin(OX), a key chemotherapy drug in colorectal cancer, can precipitate splenorenal shunts due to sinusoidal injury. We report a case of hyperammonemia post oxaliplatin therapy. A 72-year-old male patient who had undergone surgical resection for(RS)rectal cancer with hepatic metastasis had been receiving capecitabine plus OX(CAPOX)as adjuvant chemotherapy. During his 7th course of treatment, he visited the outpatient clinic with complaints of weakness, dysarthria, and urinary incontinence. Laboratory findings showed an elevated NH3 level (200 μg/dL), and subsequent abdominal computed tomography revealed a splenorenal shunt, which was attributed to OX. Balloon-occluded retrograde transvenous obliteration(BRTO)was then performed. The patient has been routinely followed up in the outpatient clinic and has had no recurrence of hyperammonemia or cancer 14 months after the procedure. In retrospect, the splenorenal shunt was present on his first visit, therefore, hyperammonemia could have been prevented at the time of commencement of chemotherapy. We report our case, along with the relevant literature.

Background The aim of this study is to determine the outcomes and prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative hepatectomy. Methods Clinical, histopathological, and treatment data of 53 patients with recurrent cholangiocarcinoma after curative resection from 2005 to 2015 at our institutes were investigated and analyzed by univariate and multivariate analyses (E-788). Results Recurrent cholangiocarcinoma occurred in 53 of 97 patients who underwent curative resection for intrahepatic cholangiocarcinoma. The median overall survival after recurrence was 13.6 months (range, 1–55 months). Multivariate analysis revealed that recurrent treatment without surgery (p = 0.0007), gross appearance except for mass-forming type (p = 0.0183) and bile duct invasion at the initial surgery (p = 0.0093) were significant poor prognostic factors in recurrent cholangiocarcinoma. Median survival of patients after surgical treatment for recurrent cholangiocarcinoma was 36.7 months versus 13.1 months in patients who did not undergo surgery (p = 0.029). Conclusions Surgical treatment, gross appearance in mass-forming type and the absence of bile duct invasion were independent favorable factors for survival among patients with recurrent cholangiocarcinoma. We recommend surgical treatment for localized recurrence, even if it occurs early after the initial hepatectomy.

Key Clinical Message Inferior vena cava (IVC) aneurysms are extremely rare. Patients can be asymptomatic, have thrombosis, rupture, or pulmonary embolism. Thrombosis of the IVC aneurysm may mimic a retroperitoneal tumor. Surgical treatment of abdominal venous aneurysms with thrombosis is warranted and is necessary for the management of intraoperative bleeding and thrombosis.

Background: Thymic atypical carcinoid(AC) tends to have a more aggressive clinical course than typical carcinoid(TC). About 20%-30% of patients with thymic AC experience local recurrence or distant metastasis. Pancreatic metastasis of thymic AC is extremely infrequent. We experienced a case of pancreatic metastasis of thymic atypical carcinoid, in which a distal pancreatectomy was performed. Case presentation: A 50-year-old man underwent thoracoscopic resection of a mediastinal tumor in June 2009. The diagnosis was thymic AC. He also underwent an extended thymectomy in October 2011, thoracoscopic resection in October 2012, and tumor resection of the chest wall in March 2013 for recurrences. During follow up in April 2014, computed tomography (CT) revealed lymph node swelling on the ventral side of the brachiocephalic vein, around the left gastric vein, and on the left side of the celiac artery. Dynamic CT revealed a pancreatic tumor 10 mm in diameter with low enhancement. EUS-guided fine-needle aspiration (EUS-FNA) biopsy revealed the pancreatic tumor was compatible with metastasis of thymic AC. The patient underwent abdominal lymph node resection and distal pancreatectomy in June 2014. Because the lymph node on the ventral side of the branchiocephalic vein was judged as unresectable, 60-Gy radiation therapy was given in September 2014. Per pathological examination and immunohistochemistry, the final diagnosis was pancreatic metastasis of thymic AC. With several chemotherapy courses for recurrences, the patient has remained alive for eight years after the first surgery. Conclusion: AC metastasis to the pancreas is extremely rare. EUS-FNA is useful for diagnosis. Definitive determination of whether the treatment provides a survival benefit awaits further studies.

Repeat liver resection is an effective treatment approach for patients with recurrent hepatocellular cell carcinoma (HCC). However, the surgical feasibility and oncological significance of repeat laparoscopic liver resection (r-LLR) remain unproven. This study evaluates and compares the clinical outcomes of non-anatomic r-LLR applied towards recurrent HCC, with those of primary LLR (p-LLR) for primary HCC. This retrospective study reports 104 patients with HCC, treated with LLR between 2014 and 2018. Twenty eight of these patients underwent r-LLR for recurrent HCC. The clinical and surgical variables were reviewed for all cases. The analysis was limited to non-anatomic resection across both groups (r-LLR: 89% (25/28) vs. p-LLR: 80% (61/76)). There were no statistically significant differences about patient background between the two groups, with the exception of Child–Pugh classification. r-LLR surgical techniques included single-site laparoscopic adhesiolysis (32%, 8/25), Pringle maneuver (8%, 2/25), and crush–clamp method using BiClamp for hepatic parenchymal transection (72%, 18/25). No severe postoperative complications were observed in the r-LLR group. Postoperative hospital stays and procedure-related postoperative survival were similar for both groups. Non-anatomical r-LLR renders comparable surgical and oncological outcomes. Our data suggest that non-anatomical r-LLR is a safe and feasible therapeutic approach to recurrent HCC.

Repeat hepatectomy is an acceptable treatment for recurrent hepatocellular carcinoma (HCC). However, repeat laparoscopic liver resection (LLR) has not been widely adopted due to its technical difficulty. This study aimed to assess the feasibility and efficacy of repeat LLR compared with repeat open liver resection (OLR) for recurrent HCC. We performed 42 repeat OLR and 30 repeat LLR for cases of recurrent HCC between January 2007 and March 2018. This study retrospectively compared the patients’ clinicopathological characteristics and operative and short-term outcomes including surgical time, intraoperative blood loss, duration of hospital stay, and postoperative complications between the two groups. There were no significant differences in patient characteristics between the two groups except in terms of Child–Pugh grade. The repeat LLR group had lower median intraoperative blood loss (100 mL vs. 435 mL; P = 0.001) and shorter median postoperative hospital stay (10 days vs. 14.5 days; P = 0.002). The other results including postoperative complications were comparable between the two groups. Further, comparison of two subpopulations of the repeat LLR group stratified by previous hepatectomy type (open or laparoscopic) or tumor location (segments 7 and 8 or other) revealed no significant differences in the postoperative clinical characteristics between them, although the morbidity rate tended to be higher in patients who underwent open hepatectomy for primary HCC than in patients who underwent laparoscopic hepatectomy. Repeat LLR for recurrent HCC is feasible and useful with good short-term outcomes although an appropriate patient selection seems to be necessary.

We report a case of pneumonectomy followed by radical pancreatectomy after oral administration of TS-1 for pancreatic cancer with complications ofa lung tumor. The patient was a 66-year-old woman. A pancreatic tail tumor and 2 lung nodules were detected on CT scans, and were diagnosed as pancreatic cancer and metastatic lung cancer. During a total of1 1 courses ofTS -1 therapy, the pancreatic tumor tended to contract, but both pulmonary nodules remained unchanged. Due to differences in treatment effect, double cancers of the lung and pancreas were suspected, rather than metastatic lung cancers. We performed a VATS partial resection of the left lower lobe for diagnostic therapy. The pathological diagnosis revealed an inflammatory myofibroblastic tumor and a primary lung cancer. We diagnosed that a radical pancreatectomy was possible and performed distal pancreatectomy. Pathological diagnosis confirmed an invasive pancreatic ductal carcinoma. Oral administration ofTS -1 was performed as adjuvant chemotherapy after surgery. Liver metastasis was observed 10 months after pancreatectomy, and GEM therapy was initiated. Peritoneal dissemination was observed at 2 years following pancreatectomy, and the patient died at 2 years and 9 months. TS-1 therapy for synchronous lung tumors and pancreatic cancer with careful observation allowed for a definitive radical resection. This method was an effective treatment for lung nodules with pancreatic cancer.

Hepatopulmonary syndrome (HPS) is a severe complication in patients with chronic liver disease with poor prognosis. Liver transplantation (LT) is a promising treatment for HPS; however, very severe HPS, which is defined by an arterial oxygen pressure (PaO2 ) of less than 50 mmHg and a right-left intrapulmonary shunt rate of more than 20%, may be a contraindication to LT, including living donor LT (LDLT). Here, we report two cases of decompensated liver cirrhosis with very severe HPS which were resolved after adult-to-adult LDLT including ABO-incompatible LDLT. Both patients required oxygen supportive therapy in combination with specialized respiratory care postoperatively, followed by improvement of oxygenation and substantial decreases of intrapulmonary shunt rate. These findings suggest very severe HPS can be resolved by LDLT, including ABO-incompatible LDLT, and reduced graft volume did not impede the reversal of intrapulmonary shunting. Our current report may indicate that adult-to-adult LDLT, including ABO-incompatible LDLT, is becoming an effective therapeutic method and prompt a review of previous reports as well as our own files with particular regard to the indication of LDLT for decompensated liver cirrhosis with very severe HPS.

Previously, we detected B cells expressing receptors for blood group A carbohydrates in the CD11b(+)CD5(+) B-1a subpopulation in mice, similar to that in blood group O or B in humans. In the present study, we demonstrate that CD1d-restricted natural killer T (NKT) cells are required to produce anti-A antibodies (Abs), probably through collaboration with B-1a cells. After immunization of wild-type (WT) mice with human blood group A red blood cells (A-RBCs), interleukin (IL)-5 exclusively and transiently increased and the anti-A Abs were elevated in sera. However, these reactions were not observed in CD1d(-/-) mice, which lack NKT cells. Administration of anti-mouse CD1d blocking monoclonal Abs (mAb) prior to immunization abolished IL-5 production by NKT cells and anti-A Ab production in WT mice. Administration of anti-IL-5 neutralizing mAb also diminished anti-A Ab production in WT mice, suggesting that IL-5 secreted from NKT cells critically regulates anti-A Ab production by B-1a cells. In nonobese diabetic/severe combined immunodeficient (NOD/SCID/γc(null)) mice, into which peripheral blood mononuclear cells from type O human volunteers were engrafted, administration of anti-human CD1d mAb prior to A-RBC immunization completely inhibited anti-A Ab production. Thus, anti-CD1d treatment might constitute a novel approach that could help in evading Ab-mediated rejection in ABO-incompatible transplant recipients.

Eosinophilic pancreatitis (EP) is a rare disease characterized by eosinophilic infiltration of pancreatic parenchyma. Although the etiology of EP is not fully understood, there may be some allergic mechanisms related to the disease. Here we report on an EP patient with psoriasis vulgaris. A 47-year-old man was admitted with cardiac space pain and a feeling of abdominal compression. He had a history of psoriasis vulgaris treated with steroid ointment for the past 30 years. Laboratory findings revealed elevated serum titers amylase. An abdominopelvic computed tomography scan showed a cystic lesion 45 mm in diameter localized in the pancreatic tail. He was diagnosed with pancreatic pseudocyst and conservative medical treatment was initiated with antimicrobial drugs and gabexate mesilate. Whenever meals were taken, pancreatitis aggravation returned. Eosinophilic leukocytosis occurred during steroid administration. Pseudoaneurysm in the splenic artery solution part occurred and a splenic artery embolism was performed in interventinal radiology. The patient underwent distal pancreatectomy. The operation specimen revealed eosinophilic infiltration. Despite the unusual occurrence of EP, it should be considered in the differential diagnosis of patients with allergic disease or with an eosinophillia group presenting pancreatitis. In such cases, EUS-FNA or laparoscopic biopsy should be mandatory to avoid unnecessary surgical operation.

Minimally invasive surgery for liver resection still remains controversial. The present study was designed to compare open versus laparoscopic liver resection (LLR). Between January 2012 and December 2013, LLR was performed on 30 patients at our institution. We performed partial hepatectomy through a pure laparoscopic method and anatomical hepatectomy by a laparoscopy-assisted method. We performed a retrospective review of these patients. The study comprised 25 men and 5 women with a mean age of 70.5 years. All patients had a liver function of Child-Turcott-Pugh classification A. The mean diameter of the tumors was 20.8 mm. Thirteen cases were resected by the pure method and 17 cases underwent the hybrid method. Nineteen patients underwent partial hepatectomy, 8 patients underwent subsegmentectomy, and 3 patients underwent segmentectomy. Mean intra-operative bleeding was 403.7 ml, and mean operating time was 316.4 min. No patients developed severe postoperative complications. We compared 19 laparoscopic partial hepatectomies (LLR-P) with 9 open partial hepatectomies. Although, no significant differences were observed in perioperative factors, both length of hospital stay and the frequency of analgesic administration were significantly reduced in LLR-P. Furthermore, we compared 13 laparoscopic (sub) segmentectomies (LLR-S) with 11 open cases. The operation time of LLR-S were longer than those of open cases, whereas no significant differences were detected in blood loss in these procedures. All length of hospital stay favored the LLR-S group. In these series comparing laparoscopic and open liver resections, there were no severe complications observed in the LLR group and there was significant rapid recovery in the LLR group, even for resections involving (sub) segmentectomy by the hybrid method.

Myxofibrosarcoma(MFS)is one of the most common sarcomas in the extremities of elderly patients.We report a rare case of MFS originating in the retroperitoneum.A 65-year-old man presented to our hospital with an intraabdominal tumor, which was identified by abdominal CT during an investigation of an abdominal protuberance.Contrast -enhanced CT and MRI revealed a 18×12 cm mass in the left retroperitoneum.The patient underwent retroperitoneum tumor resection.Operative findings showed that there was an indistinct area between the left side of the tumor and the abdominal wall.There was no residual tumor macroscopically after the operation.The histopathological diagnosis was MFS arising from the retroperitoneum. Four months later, local recurrence and para-aortic lymph node metastasis were diagnosed.We performed tumor resection; however, the recurrent tumor had invaded the iliopsoas and iliac muscles.Additionally, there was peritoneal dissemination around the tumor.Five months after the initial surgery, a recurrence on the back was identified.He died 7 months after the first operation.According to previous reports, patients who undergo an operation with pathologically negative margins achieve better surgical outcomes.Therefore, it is important to perform expanded resection with enough surgical margin as possible.

A 65-year-old woman had received chemotherapy for malignant lymphoma since 2011. After the 8th course, computed tomography revealed the disappearance of lymph node metastasis, except for 22mm of the mass located on the tail side of the antrum. MRI showed a low intensity mass on the T1 and T2-weighted images. FDG-PET did not show abnormal uptake in the tumor. EUS-FNA did not reveal a definitive diagnosis. We performed a laparotomy for diagnosis and treatment. Intraoperative findings showed that the tumor occurred in the mesentery of the transverse colon. The pathological diagnosis was angiomyolipoma. The patient has been free from recurrent disease for 2 years and 6 months. Angiomyolipoma originating in the transverse mesentery region is rare and, due to various percentage of tissue factors, there are no fixed view of image findings. Furthermore, a large tissue volume is need for histological diagnosis. Laparotomy is useful for diagnosis and therapy for angiomyolipoma occurring in the mesentery of the transverse colon.

A 67-year-old woman, who was diagnosed with ovarian cancer with multiple metastases, underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, para-aortic lymph node dissection(b2), omental subtotal hysterectomy, and lower anterior rectal resection after receiving a combination of PTX plus CBDCA chemotherapy. Macroscopically, complete resection was achieved and histopathological examination of the resectedspecimen showedpoorly differentiatedserous adenocarcinoma. After surgery, additional chemotherapy was administered. However, increasing only lesser curvature of stomach lymph node, we performed laparoscopic lymph node resection as debulking surgery. It is often said that macroscopic complete resection of ovarian cancer improves the prognosis. In particular, we hope that this patient will survive longer with a sustainable quality of life as a result of laparoscopic stomach- andnerve -sparing surgery.

Esophageal cancer rarely metastasizes to the brain. The authors experienced a case of esophageal carcinoma which metastasized to the cerebellum as the first presentation. A 61-year-old man was identified as having esophageal carcinoma by esophagogastroduodenoscopy during a medical checkup. Subtotal esophagectomy with dissection of 3 regional lymph nodes was performed. The tumor was 30 × 20 mm2 in size, and was revealed to be a moderately differentiated squamous cell carcinoma. The pathological finding was T1b(SM)N0M0 stage I. Fourteen months after the surgery, the patient complained of nausea. Brain magnetic resonance imaging (MRI) showed a cystic tumor of 42 × 28 × 28 mm3 in size in the central cerebellum. No other metastasis was pointed out. A craniotomy for brain tumor resection was performed, and the histopathological examination revealed that it was a metastatic carcinoma from the esophagus. Gamma knife therapy was added. The patient died of cerebellar metastasis recurrence 24 months after the first surgery.

The strategy for treating extremely aged patients with gastric carcinoma is controversial. This study reviews the prognoses of patients aged 85 years and older who were diagnosed with gastric carcinoma.One hundred seventeen patients aged 85 years and older were diagnosed as having gastric carcinoma after 1969 in our institution. After excluding those at stage IV, 36 cases underwent curative resection and 30 cases received best supportive care (BSC), which we reviewed retrospectively.Surgical methods included distal gastrectomy for 28 cases, total gastrectomy for five cases, and other procedures for three cases. Postoperatively, pneumonia developed in four cases, anastomotic leakage in two cases, and pancreatic fistula in one case. Two patients died of pneumonia within 1 month of surgery. Univariate analysis demonstrated that age, surgery, performance status, and sodium level were statistically significant prognostic factors. Multivariate analysis demonstrated that surgery was the only independent prognostic factor. When patients with a performance status of 4 were excluded, the clinical characteristics of the surgery group (n = 36) and BSC group (n = 20) were statistically identical, and the overall survival was significantly better in the surgery group (p = 0.0078).Postoperative outcomes were relatively acceptable. Surgery may be feasible and beneficial even for extremely aged patients 85 years and older, except for those with a performance status of 4.

Summary Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV-related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor-specific hyporesponse with a well-maintained response to the third-party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third-party stimulus were unable to do so. Thus, inducing an anti-donor-specific immunosuppressive status by minimizing immunosuppression should enable post-transplant HBV vaccination to be a promising prophylactic strategy.

Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)–infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P < 0.001). Furthermore, the PLT count of patients with thrombocytopenia (PLT count ≤ 5 × 104/mm3) increased significantly in the group without splenomegaly (SV/BSA value < 400) versus that in the group with splenomegaly (P = 0.005). Thus, if both splenomegaly and thrombocytopenia coexist (PLT count ≤ 5 × 104/mm3 and SV/BSA value ≥ 400), persistent thrombocytopenia is predictable after LTx. Liver Transpl 15:208–215, 2009. © 2009 AASLD.

Background. Congestion in the right paramedian sector of a right liver graft without a middle hepatic vein (MHV) may lead to graft dysfunction. To solve this problem, we have developed a technique for reconstructing the MHV tributaries of the right liver grafts by using the preserved recipient's native MHV trunk. Methods. Between 2005 and 2007, among 34 right liver graft liver transplant patients with significant MHV tributaries (>5 mm in diameter), 21 patients underwent right liver graft living-donor liver transplantation: draining MHV tributaries with recipient's native MHV trunk. We evaluated the patency of the reconstructed MHV tributaries, graft regeneration, and graft survival. Results. The 3-month patency rates of the reconstructed V8 and V5 were 92% and 76%, respectively. The 1-year survival rate and the regeneration index of the right paramedian sector 6 months after transplantation were higher in patients with reconstructed MHV tributaries than that for patients without reconstructed MHV tributaries. Conclusion. The use of the recipient's MHV trunk for the reconstruction of the MHV tributaries of the right liver grafts is considered to be a valuable and a feasible strategy in right liver graft living-donor liver transplantation.

We report a case of small intestinal adenocarcinoma treated with laparoscopic surgery. A 70-year-old woman had abdominal pain and epigastralgia. There were no abnormal findings on upper and lower endoscopy. The symptoms continued for 4 months after endoscopy, so she presented to our hospital. After CT examination, small bowel cancer with ileus was suspected. An ileus tube was inserted to relieve the bowel pressure and she was diagnosed with ileum cancer by enteroscopy. Laparoscopic surgery was performed and the pathological stage was determined as pStage Ⅲa. She was treated with oral chemotherapy (UFT plus LV) and had no recurrence 6 months after surgery.

The aim of this study was to compare the efficacy of self-expandable metallic stent (SEMS) and transanal tube as preoperative treatments for left-sided obstructive colon cancer. Forty-three patients (the SEMS group: 28 cases, the tube group: 15 cases) were included in this study. Clinicopathological data (age, sex, tumor location, depth, histological type, stage) were comparable between the 2 groups. In addition, there was no difference in intestinal decompression rate between the SEMS group and the tube group (technical success rate: 100% vs 86.7%, clinical success rate: 92.8% vs 73.3%, complication rate: 7.1% vs 0%). A significantly higher number of patients in the SEMS group underwent laparoscopic surgery because of difference of historical background. However, no significant difference was observed between the 2 groups in postoperative outcome(complication rate, hospital stay duration). SEMS insertion had several benefits compared to transanal tube placement, such as the resumption of oral intake because of rapid resolution of obstruction and easier management because SEMSs do not require washing. SEMS insertion could be a safe and effective bridge to subsequent surgery in patients with left-sided obstructive colon cancer.

We have described our experience with arterial reconstruction during living-donor liver transplantation by using Varioscope AF3--a head-mounted surgical binocular system with automatic focusing and continuous zoom magnification from 3.6x to 7.2x. From July 1996 to December 2006, 91 grafts were implanted in 89 living-donor liver transplantation recipients, including two that required retransplantation. For microsurgical reconstruction of the graft hepatic artery, a conventional operating microscope was used in the first 10 transplants and Varioscope, in the subsequent 81. The time required to complete arterial reconstruction while using a conventional operating microscope and Varioscope was 78.6 +/- 44.6 min and 35.5 +/- 15.5 min, respectively. No arterial complications, including hepatic artery thrombosis, occurred in any of the 89 patients during the observation period. In living-donor liver transplantation, successful hepatic artery reconstruction can be safely carried out using Varioscope.

A 70-year-old woman who complained of abdominal pain and a prolapsed tumor from the anus was diagnosed with an intestinal obstruction resulting from anal canal cancer. Computed tomography (CT) and magnetic resonance imaging revealed a huge tumor (11×5×12 cm) invading the vagina and levator ani muscle. Enlarged inguinal lymph nodes on both sides indicated metastasis. The clinical stage was T4b (vagina, levator ani muscle, and pudenda) N0H0M1a (LYM), stage IV (Japanese Classification of Colorectal Carcinoma: 8th edition). As curative resection was not possible, a transvers colostomy was performed to relieve the intestinal obstruction. This was followed by chemoradiotherapy (45 Gy/1.8 Gy×25; TS-1, 80 mg/body for 2 weeks and a 1-week interval, for 2 courses) and up to 10 courses of Bev+mFOLFOX6 continuously. After this regimen, there was a remarkable reduction in tumor size. Positron emission tomography-CT revealed no FDG uptake in the primary rectal site or inguinal lymph nodes, but a maximum standardized uptake value (SUVmax) of 6.3 was detected in the vagina. Six weeks after chemotherapy, the patient underwent a pelvic exenteration including resection of the vagina, bladder, and pudenda. The pathological stage was yp T4b (vagina) N0H0M0, stageⅡ. Curative resection was performed, and the patient had a Grade 2 pathological response after chemoradiotherapy.

We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

A 77-year-old-woman, whose chief complaint was anemia, was referred to our hospital and diagnosed with advanced gastric cancer with liver metastasis and lymph node metastasis.Gastrointestinal endoscopy showed a tumor on the lesser curvature of the gastric corpus.Histologically, biopsy specimens indicated adenocarcinoma with genetic amplification of human epidermal growth factor receptor type 2.Computed tomography and magnetic resonance imaging showed lymph node metastasis and liver metastasis.The patient received a total gastrectomy and a partial liver resection after combination chemotherapy consisting of capecitabine, cisplatin, and trastuzumab.Histopathological examination of a resected specimen showed a minute residual cancer nest at the subserosa of the stomach and lymph node metastasis, but no liver metastasis. This combined modality therapy can be considered an effective treatment for gastric cancer with liver metastasis, and we hope that it will be established as a standard therapy.

Near-infrared spectroscopy (NIRS), which enables non-destructive evaluation of hemoglobin (Hb) oxygenation and the redox state of cytochromeoxidase (Cyt.aa3) in living tissues, has been employed during surgery to detect possible impairment of hemodynamics and mitochondrial respiration in the anterior segment of a right lobe liver graft in living-donor liver transplantation (LDLT). Thirty-six patients undergoing LDLT using a right lobe graft without the middle hepatic vein (MHV) were enrolled in this study. During the course of harvesting and implantation, NIRS measurements were performed on the anterior segments of the liver grafts. In two recipients of liver grafts with Hb residue over 70% in the anterior segment after ex vivo flushing, the MHV tributary was reconstructed, while it was not reconstructed in the other 34 recipients. Of those 34 recipients, 16 recipients of liver graft with 40-70% Hb residue showed transient increase of transaminase levels after LDLT. Of those 16 recipients, six recipients who showed reduction in oxidized Cyt.aa3 in the anterior segment suffered from persistent hyperbilirubinemia after LDLT. In patients showing impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries, reconstruction of the MHV tributaries might have a beneficial effect.

The purpose of this study was to evaluate the diagnostic capability of gadoxetate disodium (Gd-EOB)-MRI for the detection of hepatocellular carcinoma (HCC) compared with multidetector CT (MDCT). Fifty patients with 57 surgically proven HCCs who underwent Gd-EOB-MRI and MDCT from March 2008 to June 2011 were evaluated. Two observers evaluated MR and CT on a lesion-by-lesion basis. We analyzed sensitivity by grading on a 5-point scale, the degree of arterial enhancement and the differences in histological grades in the diffusion-weighted images (DWI). The results showed that the sensitivity of Gd-EOB-MRI was higher than that of MDCT especially for HCCs that were 1 cm in diameter or smaller. The hepatobiliary phase was useful for the detecting of small HCC. We had few cases in which it was difficult to judge HCC in the arterial enhancement between MRI and MDCT. In the diffusion-weighted image, well differentiated HCC tended to show a low signal intensity, and poorly differentiated HCC tended to show a high signal intensity. In moderately differentiated HCC's, the mean diameter of the high signal intensity group was larger than that of the low signal intensity group (24.5 mm vs. 15.8 mm). In conclusion, Gd-EOB-MRI tended to show higher sensitivity compared to MDCT in the detection of HCC.

A 58-year-old man was admitted to the author's institution with complaints of dysphagia and tarry stool. An advanced squamous cell carcinoma of the esophagogastric junction was revealed by endoscopy. The clinical stage was GE, T4, N1, H0, M0, cStageIVa, according to the Japanese Classification of Esophageal Cancer. Low-dose FP chemotherapy(continuous 5-FU div of 500mg/day with intermittent CDDP div of 10mg/day)was used. The tumor size was remarkably reduced while the side effects were trivial. A clinically complete response was recognized with CT and with pathological findings from endoscopic biopsy. As a recurrence was diagnosed in the off-treatment period, the same regimen was resumed. Soon, a complete response was again. The patient is doing well with no reoccurrence after almost 10 years, with a low-dose FP chemotherapy.

Budd-Chiari syndrome (BCS) results from diverse causative factors. Myeloproliferative disorders (MPDs) including essential thrombocythemia (ET) account for a minority of BCS cases in Japan. ABO-blood-type incompatible living donor liver transplantation (LDLT) in adults has become an acceptable procedure owing to the development of new strategies for preventing antibody-mediated rejection. This report presents a rare case of BCS secondary to ET, which was cured by an ABO-incompatible (AB to A) LDLT. In this case, prostaglandin E(1) and gabexate mesilate were administered into portal vein and rituximab prophylaxis was applied. No splenectomy was performed as it is in most ABO-incompatible cases, since a flow cytometry showed no anti-B antibodies in the splenocytes collected by a wedge biopsy during the LDLT. The postoperative course was uneventful. Anti-coagulation therapy was initiated with aspirin and warfarin instead of hydroxyurea. This report describes an ABO-incompatible LDLT without a splenectomy for BCS secondary to ET.

Although antiviral prophylaxis with the combined high-dose hepatitis B immunoglobulin (HBIg) and lamivudine therapy has effectively reduced post-liver transplantation recurrence of hepatitis B virus infection, its use is limited by cost and availability.Fourteen living-donor liver transplant patients were performed with the mean follow-up of the 23 months (range, 5 to 58 months). We examined the effectiveness of prophylaxis against recurrence of hepatitis B with much lower dose of HBIg. HBIg (10000 IU/day) was two or three times intra- and postoperatively administered and then the serum titers of HBIg was maintained at more than 100 IU/mL.Although two patients were preoperatively HBV-DNA positive (DNA concentrations were 4.4 and 4.7 LGE, respectively) by a transcription-mediated amplification assay (TMA) method, all 14 patients postoperatively became HBV-DNA-negative and HBsAg-negative.Our protocol of the combination low-dose HBIg and lamivudine therapy prevents the recurrence of hepatitis B and is likely to be more cost-effective than high-dose HBIg regimens. Further study is needed to develop the combination therapy of the optimal dose of HBIg and lamivudine.

We demonstrated a novel strategy for specific and persistent inhibition of antibody (Ab) production against blood group A or B carbohydrate determinants necessary for successful ABO-incompatible transplantation. Similar to human blood group O or B individuals, mice have naturally occurring Abs against human blood group A carbohydrates in their sera. B cells with receptors for A carbohydrates in mice belonging to the CD5+CD11b+B-1a subset have phenotypic properties similar to those of human B cells. These cells could be temporarily eliminated by injecting synthetic A carbohydrates (GalNAcα1–3, Fucα1–2Gal) conjugated to bovine serum albumin (A-BSA) and anti-BSA Abs. In mice that received the injection of A-BSA/anti-BSA Abs, the serum levels of anti-A IgM were reduced, but immunization with human A erythrocytes resulted in increased serum levels of anti-A Abs. When combined with cyclosporin A (CsA) treatment, which blocks B-1a cell differentiation, and treatment with A-BSA/anti-BSA Abs, the serum levels of anti-A Abs were persistently undetectable in the mice even after the immunization. B cells with receptors for A carbohydrates were markedly reduced in these mice. These results are consistent with the hypotheses that treatment with A-BSA/anti-BSA Abs temporarily depletes B cells responding to A determinants, and CsA treatment prevents the replenishment of these cells.

In a 12-year-old patient with blood group O, who had received a partial liver graft 10 years ago from his father with blood group A, the levels of anti-A-specific antibodies (Abs) were persistently undetectable after the transplantation, while the levels of anti-B-specific Abs gradually increased and attained a plateau. Peripheral blood mononuclear cells (PBMCs) from this patient were engrafted into NOD/SCID mouse in order to investigate the immune response to donor-type blood group antigens. Even after sensitization with blood group-A erythrocytes, no anti-A Abs were detected in the serum samples of the mouse that received PBMCs from the blood group-O recipient of group-A liver allograft, however, immunoglobulins specific for antigens other than the A antigens were produced. Thus, we provide a possible evidence of immune tolerance to blood group antigens in this ABO-incompatible pediatric liver transplantation.

Neurological complications (NCs) represent a serious problem following liver transplantation and may develop either because of various peri-operative factors or the toxicity of immunosuppression. Although the causality assessment of NCs can be particularly difficult in the setting of organ transplantation, calcineurin inhibitors (CNIs) might influence NCs to a certain extent, regardless of the etiology. Therefore, minimizing the influence of CNIs could be a reasonable strategy for alleviating NCs. Based on our hypothesis that lipid supplementation prevents lipophilic CNIs from crossing the blood-brain barrier, soybean oil was administered to five liver transplant patients with NCs. In all of these patients, the neurological symptoms improved without discontinuing or reducing the dose of CNIs. Thus, lipid supplementation might be able to reduce the adverse neurological effects of CNIs.

Circulating tumor cells (CTCs) are thought to be “metastatic intermediates”. Recently, we reported encouraging survival rates following neoadjuvant therapy using gemcitabine (Gem) and S-1 concurrently with radiotherapy (NACRT) in patients (pts) with resectable pancreatic cancer (PC). However, NACRT may have disadvantages. We hypothesized that NACRT in PC may induce epithelial to mesenchymal transition (EMT), which is associated with metastasis followed by the increase of CTCs. To extend our assessment of EMT during NACRT, we investigate the results of the v-hCTC detection in the pts treated with NACRT. This study was a single institution trial, approved by the Kure Medical Center IRB. Pts with resectable cytologically or histologically proven ductal adenocarcinoma of the pancreas were enrolled. Treatment consisted of an intervenous infusion of Gem 800 mg/m2 on day 1, 8, 22, and 29; and S-1 80 mg/m2 orally on day 1-5, 8-12, 22-26, and 29-33 given concurrently with IMRT to 60 Gy (2 Gy/day, 5 times per week, 30 fractions). Surgical exploration was scheduled 4-7 weeks after the final radiation fraction. To detect v-hCTCs, we employed a telomerase-specific replication-selective adenovirous expressing GFP (TelomeScan F35). 7.5 ml of blood samples were obtained from the pts included in this clinical study before NACRT, after 1 month of NACRT, and after 2 months of surgical resection. To distinguish between leucocyte and cells with epithelial origin, cells were stained with anti-CD45 and anti-Cytokeratin Abs. To distinguish cells with mesenchymal origin, cells were labeled with anti-Vimentin Ab. GFP-positive and CD45-negative cells were counted as v-hCTC. 12 pts aged 44-77 years (2 males and 10 females) were enrolled. No treatment-related deaths occurred. CA19-9 was reduced to Citation Format: Masahiro Tanemura, Toshimitsu Irei, Masashi Inoue, Shinya Yamashita, Kenta Furukawa, Masaki Wakasugi, Kentaro Kishi, Hiroaki Nagano, Hiroki Akamatsu, Yasuo Urata, Nobuyoshi Hatanaka, Masaki Mori, Yuichiro Doki. The detection of viable human circulating tumor cells (v-hCTCs) in resectable pancreatic cancer induced by neoadjuvant chemoradiotherapy (NACRT) using gemcitabine, S-1 and intensity-modulated radiotherapy (IMRT). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 556. doi:10.1158/1538-7445.AM2015-556

It was recently reported that the induction of endotoxin tolerance (ET), which is defined as a reduced response to a lipopolysaccharide (LPS) challenge following the first LPS encounter, inhibits major histocompatibility complex (MHC)-restricted antigen presentation. This raises the question whether alloimmune responses can be inhibited by inducing ET in transplant donors. C57BL/6 mice were treated with a low dose of LPS prior to a challenge with a high dose of LPS to induce ET. Hearts from endotoxin-tolerized C57BL/6 mice were transplanted to BALB/c mice. The survival of the endotoxin-tolerized heart allografts was significantly prolonged. By using irradiated splenocytes from C57BL/6 mice and allogeneic splenocytes from BALB/c mice, a mixed lymphocyte reaction (MLR) assay was performed. The MLR assay used CFSE, and revealed that the splenocytes from the endotoxin-tolerized mice failed to induce the proliferation of allogeneic CD4(+) and CD8(+) T cells. Cytokine analyses of the supernatant of the MLR culture using endotoxin-tolerized stimulators revealed a distinct shift in the Th 1/Th 2 balance toward the Th 2-type response. The induction of ET increased the proportion of myeloid-related dendritic cells (DCs) expressing molecules necessary for antigen presentation, which favor the development of a Th 2 response; however, it reduced the proportion of lymphoid-related DCs expressing those molecules, which favor the development of the Th 1 response. Although the relevance of these findings with regard to the prolonged survival of the endotoxin-tolerized heart allografts remains to be elucidated, this is the first study to demonstrate that the induction of ET in donor animals inhibits alloimmune responses.

We investigated the effects of whole cell vaccination with α-gal epitopes-expressing pancreatic cancer (PC) cells (Cancer Res; 70 (13); 5259-69, 2010) and examined the usefulness of this vaccine in the induction of specific anti-tumor-responses and improvement of survival. But, these effects were somewhat weak. We hypothesized that tumor lysate (t-ly), which contains many tumor-associated antigens (TAAs) of both PC and stromal cells is a suitable vaccination material and it can elicit a broadly protective anti-tumor responses. In this study, we investigate that vaccination with α-gal epitopes-expressing PC t-ly can induce cross-reactive protections to heterosubtypic PC cells. Human PC cell lines, BxPC3 (Bx), expressing Mesothelin, and MiaPaCa (Mia), expressing MUC1 were employed. PC cell lines were injected s.c. into NOD/SCID mice. The grown tumors were enucleated and homogenized for making t-ly. To synthesize α-gal epitopes on t-ly, we cloned the α1,3 galactosyltransferase (α1,3GT) cDNA from a New World monkey and isolated a soluble form of enzyme in the yeast expression system of Pichia pastoris. These t-lys were incubated with UDP-Gal and α1,3GT. α1,3GT KO mice were immunized with pig tissues to produce anti-Gal Ab. The high anti-Gal KO mice were vaccinated intraperitoneally by either parental (control group; Bx-t-ly or Mia-t-ly) or α-gal-t-ly (α-gal group; α-gal-Bx-t-ly or α-gal-Mia-t-ly). No expression of α-gal epitopes were observed in parental t-lys, whereas high expression levels were clearly detected on α-gal-t-lys. α-gal-Bx-t-ly vaccination elicited strong responses of anti-Bx IgG and anti-Mesothelin IgG, whereas Bx-t-ly vaccination did not induce such Ab responses. For Mia-t-ly vaccination, KO mice of α-gal group clearly induce anti-Mia IgG and anti-MUC1 IgG, but no Ab responses were observed in control group. Productions of either anti-Bx or anti-Mia IgG in α-gal group were 64-fold higher than those in control group. α-gal-Bx-t-ly vaccinated KO mice abundantly produced cross-reactive IgG Abs to Mia cells, whereas no cross-reactive humoral responses to Mia cells were induced by Bx-t-ly vaccine. Vaccinated mice sera from α-gal-Mia-t-ly strongly cross-react to Bx cells. To demonstrate in vivo tumor destruction, splenocytes from vaccinated KO mice were prepared, and these splenocytes were inoculated i.p. into NOD/SCID mice. Either live Bx or Mia cells were challenged with s.c. injection. Both Bx and Mia tumors in mice inoculated from parental group reached the size of 100 mm2 at approximately 22 days after injection. For tumors in mice transferred from α-gal group, no regrowth tumors were identified. We conclude that α-gal epitopes-expressing t-ly vaccine can elicit durable and broadly protective immune response to subtypic PC cells, and that such vaccination may provide implications for a universal cancer vaccine to cure for the patients with PC. Citation Format: Masahiro Tanemura, Eiji Miyoshi, Hiroaki Nagano, Masafumi Inoue, Toshimitsu Irei, Shinya Yamashita, Kenta Furukawa, Katsuyoshi Matsunami, Wataru Kamiike, Masaki Mori, Yuichiro Doki. Strong cross-reactive responses to pancreatic cancer cells induced by α-gal epitopes-expressing tumor lysate and their implications for a universal cancer vaccine. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2560. doi:10.1158/1538-7445.AM2014-2560

Current strategies in the treatment of advanced pancreatic cancer (PC) offer little hope for a cure. Now treatment modalities, including immunotherapy are warranted for PC, which easily metastasizes in many organs. Although MUC1 and Mesothelin are potential targets for the immunotherapy, vaccination against a single tumor-associated antigen (TAA) seems to be insufficient. In our previous study, we showed the in vitro and in vivo effectiveness of immunotherapy though vaccination with whole PC cells engineered to express α-gal epitopes (Cancer Res; 70(13); 5259-69, 2010). It was thought that the immunogenicity of well-known as well as unknown multiple TAAs in cancer cells was upregulated by addition of α-gal epitopes and these TAAs ultimately lead to polyclonal expansion of both B and T cells. For clinical development of more effective immunotherapy, we proposed that human tumor lysate originated from resected PC is more suitable because it contains several TAAs that could elicit a marked anti-tumor response. The present study addresses the effectiveness of elicitation of both antibody production and in vivo destruction against PC by vaccination with human tumor lysate from PC patients, expressing α-gal epitopes enzymatically. Tumor specimens were obtained from 11 patients at the time of surgical resection. To express α-gal epitopes, we cloned the α1,3galactosyltransferas (α1,3GT) from a New World Monkey and expressed it in a soluble form in the yeast expression system of Pichia pastoris. For synthesis of α-gal epitopes, tumor tissues were homogenized in MES buffer, and incubated with MnCl2, UDP-Gal and α1,3GT for 4 hours at 37°C. α1,3GT KO mice were immunized with pig tissue to generate anti-Gal Ab in their sera. These mice were vaccinated intraperitoneally by either unsynthesized (control group) or α-gal tumor lysate (α-gal group). Production of anti-PC cell Ab in α-gal group was 4∼8-fold higher than that of control group. Anti-TAA Ab production was also markedly increased in comparison with that in control group (anti-MUC1 2-fold, anti-Mesothelin 4-fold). Expansion of TAAs-specific B cells was significantly higher [number of spots at 1×106 splenocytes: MUC1: α-gal vs. control; 414±26 vs. 178±46 (p=0.015), Mesothelin: 401±56 vs. 209±19 (p=0.03)]. To demonstrate in vivo tumor destruction, an animal experiment was performed. Splenocytes from vaccinated KO mice were prepared, and then transferred intraperitoneally (90×106 cells) into NOD/SCID mice. Followed by transferring, mice were challenged with 1×107 of live PANC-1 cells. In mice from α-gal group, regrowth of tumors was significantly prevented and survival period was significantly prolonged [α-gal vs. control: 91.5 vs. 43.3 days (p=0.03)]. We conclude that immunotherapy with α-gal tumor lysate obtained from PC patients with enzymatic engineering could be more effective and practicable methods for PC treatment. Citation Format: Kenta Furukawa, Masahiro Tanemura, Eiji Miyoshi, Hiroaki Nagano, Hidetoshi Eguchi, Toshimitsu Irei, Masashi Inoue, Shinya Yamashita, Yoshito Tomimaru, Naoki Hama, Hiroshi Wada, Koichi Kawamoto, Shogo Kobayashi, Katsuyoshi Matsunami, Kiyomi Taniyama, Wataru Kamiike, Masaki Mori, Yuichiro Doki. Immune-based therapy with human tumor lysate, expressing α-gal epitopes induce significant B cell response and in vivo tumor destruction against pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2884. doi:10.1158/1538-7445.AM2014-2884