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Adherence to oral nutritional supplements (ONS) to prevent weight loss after gastrectomy is problematic. The present study evaluated the impact of super energy-dense ONS (SED ONS; 4 kcal/mL) on glycemic change and energy intake after gastrectomy.Gastrectomy patients were placed on continuous glucose monitoring for a 3-day observation period after food intake had been stabilized postoperatively. In addition, they were given 0, 200, and 400 kcal/day of SED ONS on Days 1, 2, and 3, respectively. The primary outcome was the area under the curve glucose 70 mg/dL (AUC 70). The secondary outcomes were other indices of glucose fluctuation and the amount of food and SED ONS intake.Seventeen patients were enrolled. The AUC 70 did not differ significantly with or without SED ONS over the observation period. SED ONS did not cause postprandial hypoglycemia and prevented nocturnal hypoglycemia. The mean dietary intake did not change significantly during the observation period, and the total energy intake increased significantly according to the amount of SED ONS provided.SED ONS after gastrectomy increased the total energy intake without dietary reduction and it did not result in hypoglycemia.

Purpose The Nathanson liver retractor (NLR) and the snake liver retractor (SLR) are commonly used in bariatric surgery and their use is associated with some disadvantages. We developed an L-shaped liver retractor (LLR) and herein evaluated its efficacy and safety. Methods The present retrospective study enrolled patients undergoing sleeve gastrectomy in our department between June 2014 and December 2020. The patients were divided into three groups according to the liver retractor used (LLR, SLR or NLR) for a comparative analysis of the efficacy and safety of the devices. The procedural time (PT) of each retractor type, defined as the time from retractor insertion to liver fixation, was compared. Results In total, 140 patients successfully underwent laparoscopic sleeve gastrectomy. The LLR, SLR and NLR were used in 37, 91, and 12 of these patients, respectively. The PT for the LLR was the shortest. AST/ALT elevation was significantly more frequent in the NLR group than in the SLR group and tended to be less frequent in the LLR group in comparison to the NLR group (p = 0.09). The length of hospital stay in the NLR group was significantly longer in comparison to the LLR group. Conclusion Our study suggested that the LLR was superior to the conventional liver retractors used in sleeve gastrectomy.

A 29-year-old male patient underwent laparoscopic sleeve gastrectomy (LSG) for morbid obesity and was discharged without any complications. Thirteen months later, he visited the emergency room with epigastric pain. A few hours before onset, he had had a larger-than-usual meal and vomited afterwards. Enhanced abdominal computed tomography revealed a hematoma 127 × 63 mm in diameter around the stomach. Angiography revealed no extravasation or pseudoaneurysm. Upper gastrointestinal endoscopy found no ulcers or abnormality of the stapler line scar from the LSG. The patient's vital signs were stable, and his hemoglobin had not fallen below the previous day's value. Conservative treatment was therefore chosen. The patient was discharged in stable condition after 11 days of hospitalization. However, the exact source of the hemorrhage was unable to be detected on the imaging findings. In view of his clinical course and the hematoma location, omental vessels were suspected of being the source of the hemorrhage.

Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p

Background Disseminated carcinomatosis of the bone marrow (DCBM) is often associated with disseminated intravascular coagulation (DIC) and a poor prognosis. Moreover, the timing of the diagnosis varies. We presented herein the first report of a case of DCBM from gastric cancer that developed rapidly after a gastrectomy. Case presentation A 42-year-old male patient was referred to us for gastric cancer. Preoperative laboratory tests were normal. Abdominal computed tomography (CT) revealed no obvious bone metastasis, and he underwent a laparoscopic distal gastrectomy. On postoperative day (POD) 1, laboratory data indicated severe thrombocytopenia. Postoperative bleeding requiring reoperation was found. Afterwards, he complained of lower back pain. His ALP and LDH gradually became elevated. On POD 8, DIC was diagnosed. CT and bone scintigraphy showed multiple, widespread bone metastases. Based on these findings, DCBM from gastric cancer was diagnosed. Systemic chemotherapy was started on POD 12. The DIC subsided during the first course, and he was discharged on POD 21. The patient died of tumor progression 7 months later. Conclusion When thrombocytopenia is observed immediately after a gastrectomy for gastric cancer, the possibility of DCBM should be considered.

Background: The number of patients with remnant gastric cancer (RGC) following gastrectomy for gastric cancer (GC) is increasing due to the increasing number of patients undergoing function-preserving gastrectomy and improved outcomes for patients with GC. Male sex, old age, intestinal type, tumor depth, and synchronous multiple GC were all associated with RGC development in a few studies with a small number of cases. However, the risk factors for RGC development remain unclear. This study aimed to examine the clinicopathological features of patients with GC; these patients were followed up after they underwent distal gastrectomy and the potential risk factors for RGC development were evaluated.Methods: A retrospective database review of 438 patients who underwent distal gastrectomy for GC at a single institution, from 2006 to 2017, was conducted. We used Cox proportional hazards analysis to estimate the relationship between clinicopathological features, operative findings, and postoperative course with RGC development. The cumulative incidence rates of RGC were calculated using the Kaplan–Meier method.Results: We retrospectively analyzed 405 cases. The median patient age was 69 years, and the patient cohort consisted of 263 men and 142 women. The Billroth-I reconstruction method was used in 204 cases, the Billroth-II method was used in 3 cases; the Roux-en Y method was used in 198 cases. RGC was diagnosed in 11 of the 405 patients. The median follow-up period was 5 years. The cumulative incidence rates of RGC calculated using the Kaplan–Meier method were 3.0%, 4.1%, and 9.1% at 5, 10, and 15 years after distal gastrectomy, respectively. During the initial surgery, intestinal-type GC was significantly associated with RGC development (hazard ratio [HR], 4.71; 95% confidence interval [CI], 1.02–21.80; p = 0.05). Male sex (HR, 2.97; 95%CI, 0.64–13.75; p = 0.16), old age (≥70) (HR, 2.72; 95%CI, 0.78–9.47; p = 0.11), and synchronous multiple GC (HR, 1.31; 95%CI, 0.28–6.08; p = 0.37) were not associated with RGC development.Conclusions: Distal gastrectomy for intestinal-type GC was significantly associated with RGC development. Hence, patients who underwent distal gastrectomy for intestinal-type GC would require intensive endoscopic surveillance.

Background Intrahepatic artery pseudoaneurysms are mostly iatrogenic and result from hepatobiliary interventions. The incidence of intrahepatic artery pseudoaneurysms within liver tumors without prior intervention is extremely rare. We presented herein the first report of a case of an intratumoral pseudoaneurysm within a liver metastasis of gastric cancer without any prior intervention during chemotherapy. Case presentation A 59-year-old male patient underwent a distal gastrectomy and D2 lymph node dissection for gastric cancer. He was treated in the emergency room for right abdominal pain following the 4th cycle of nivolumab administration as second-line chemotherapy after adjuvant chemotherapy with S-1 and first-line chemotherapy for a liver metastasis of gastric cancer with ramucirumab plus paclitaxel. CT showed a 72-mm metastatic liver tumor containing a 9-mm pseudoaneurysm and fluid collection around the hepatic edge. Intrahepatic artery pseudoaneurysm within the metastatic liver tumor was diagnosed, with the surrounding fluid indicating potential, active bleeding. An emergency angiography confirmed the presence of a pseudoaneurysm in the intrahepatic artery, which was embolized using microcoils. The contributory causes of the intratumoral pseudoaneurysm were assumed to be the following: (1) tumor necrosis leading to encasement, erosion of the vessel wall, and subsequent arterial wall weakening; and (2) inhibition of vascular endothelial growth by ramucirumab resulting in a vessel wall breach and pseudoaneurysm formation. Conclusion It is necessary to recognize that pseudoaneurysms can arise within a metastatic liver tumor during chemotherapy.

Background Ruptured pseudoaneurysms are a rare complication of gastrectomy, but when they do develop, they are often fatal. We presented herein the first report of a case of pseudoaneurysm arising from the right inferior phrenic artery (RIPA) after a laparoscopic gastrectomy. Case presentation A 61-year-old male patient underwent a laparoscopic distal gastrectomy and D1+ lymph node dissection with Roux-en-Y reconstruction for early gastric cancer. He was discharged on postoperative day (POD) 9 without any complications, such as anastomotic or pancreatic leakage. On POD 19, he was referred to the emergency room for upper abdominal pain. Enhanced abdominal computed tomography revealed a 60 × 70 mm hematoma, indicating intra-abdominal bleeding and a 10-mm pseudoaneurysm in the RIPA. Selective digital subtraction angiography confirmed the presence of a pseudoaneurysm in the RIPA, which was embolized using multiple microcoils. Thereafter, no clinical signs were observed, and the patient was discharged from the hospital 15 days after angiography without any recurrence of bleeding. We hypothesized that the cause of the pseudoaneurysm was mechanical vascular injury due to the thermal spread of the ultrasonically activated devices (USADs) during lymphatic node dissection. Conclusion Given the thermal spread of USADs, safe and appropriate lymph node dissection based on precise anatomical knowledge is crucial to preventing postoperative pseudoaneurysms.

Preoperative hyperbilirubinemia and visualization of an appendicolith on computed tomography scan could be useful clinical indicators to establish the diagnosis of gangrenous appendicitis. These two indicators are easily assessed and thus could be readily applicable in the evaluation of patients with presumed appendicitis., Aim Patients with gangrenous appendicitis usually require emergency surgery. Preoperative diagnosis of gangrenous appendicitis is clinically important but not always straightforward. We undertook this study to identify preoperative predictors of gangrenous appendicitis. Methods This was a single‐center case–control study. We identified 162 patients who underwent appendectomy between September 2011 and August 2014 after the diagnosis of acute appendicitis was established. We identified laboratory parameters and computed tomography (CT) scan findings predictive of histologically or surgically diagnosed gangrenous appendicitis by univariable and multivariable analyses. Results Of 146 study patients, gangrenous appendicitis was confirmed in 102. Univariable analysis showed that two laboratory factors (C‐reactive protein []and total bilirubin [T‐Bil]) and three CT scan findings were significant predictors for gangrenous appendicitis. Multivariable analysis showed that T‐Bil and two CT scan findings (appendicolith and fat stranding around the appendix) were independent predictors. The combination of “T‐Bil ≥ 1.0 mg/dL or appendicolith” was able to predict gangrenous appendicitis with a sensitivity of 90.5%, positive predictive value of 80.4%, and accuracy of 77.8%. The combination of “T‐Bil ≥ 1.0 mg/dL or fat stranding around the appendix” was able to predict gangrenous appendicitis with a sensitivity of 98.9%, positive predictive value of 76.4%, and accuracy of 71.9%. Conclusion These combinations of laboratory and CT scan findings could be valuable as predictors of gangrenous appendicitis.

Objectives: The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an indicator of cancer-related inflammation. The aim of our study was to examine the prognostic value of the NLR for patients with advanced gastric cancer receiving second-line chemotherapy. Methods: The association of overall survival (OS) in second-line chemotherapy and the clinicopathological findings including NLR were analyzed retrospectively. The selection criteria were patients who received second-line chemotherapy between January 2010 and June 2015, had histologically confirmed gastric adenocarcinoma, and were followed up until death or for 180 days or longer. Results: Eighty-six patients met the selection criteria. Multivariate analysis revealed that performance status 2, hemoglobin < 10 g/dL, and NLR before first-line chemotherapy ≥3 were adverse predictive markers. NLR before second-line chemotherapy was not associated with OS. A prognostic model was constructed dividing patients into three groups according to the number of adverse predictive factors: good (no factor), intermediate (one factor), and poor (more than two factors). The median OS for the good, intermediate, and poor groups was 14.3, 7.2, and 4.4 months, respectively (p < 0.001). Conclusions: Patients with advanced gastric cancer with performance status 2, hemoglobin < 10 g/dL, and NLR before first-line chemotherapy ≥3 are not likely to benefit from second-line chemotherapy.

We present an autopsied case of non-plaque-type dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) with extensive amyloid-β (Aβ) deposition in the brain. A 39-year-old Japanese woman presented with memory disturbance and abnormal behavior. The patient had a history of craniotomy with dura matter-graft transplant for a head injury which occurred when she was 19 years old. Magnetic resonance imaging (MRI) showed hyperintensities in the cerebral cortex and striatum on diffusion-weighted images, particularly on the dura mater-grafted right side. Her clinical symptoms, including rapidly progressing cognitive impairment, myoclonus, and periodic sharp wave complexes on electroencephalogram, could not be distinguished from typical sporadic CJD cases. The patient died 11 months after symptom onset, and pathological investigations showed extensive spongiform degeneration with prion protein (PrP) deposition without Kuru plaques; these observations were essentially the same as those of typical sporadic CJD cases. Furthermore, Aβ immunohistochemistry showed extensive diffuse staining in the cerebral neocortex, plaque-type deposition, positive staining in the pia mater, and cerebral amyloid angiopathy. Although the MRI findings suggested that the pathological involvement originated from the dura mater-grafted right side, the PrP and Aβ depositions showed no apparent regionalization and laterality. Tau-pathology including neurofibrillary tangles was hardly identified. The proteins phosphorylated α-synuclein and phosphorylated transactivation response DNA-binding protein 43 kDa were not detected on immunostaining. Although this report describes only one case, various speculations were made based on detailed clinical and pathological observations in conjunction with previous reports of dCJD. In particular, this report provides significant insight into the characteristics and progression of dCJD pathology and its relationship with Aβ pathology.

Introduction: This study aimed to determine the prognostic factors and the values that predict survival after percutaneous endoscopic gastrostomy (PEG) tube placement in patients with amyotrophic lateral sclerosis (ALS). Methods: We retrospectively analyzed the correlations for 97 consecutive patients with ALS between clinical parameters and survival following PEG tube placement using the log-rank test and Cox proportional-hazards models. Results: The log-rank test showed that an arterial carbon dioxide pressure (PaCO2) of ≤ 40 mmHg (P = 0.0054), a forced vital capacity (FVC) of ≥ 38% of predicted (P = 0.0003), and bulbar-onset (P = 0.0121) were significantly associated with better post-PEG survival. Multivariate analysis showed that the FVC and PaCO2 were associated with better post-PEG survival (P = 0.0081 and P = 0.0265, respectively). Conclusions: PEG tube placement in ALS is recommended when FVC is ≥ 38% of predicted and when PaCO2 is normal. Muscle Nerve 54: 277–283, 2016

Laparoscopic sleeve gastrectomy (LSG) has wide-ranging positive effects on adipocytokine metabolism, bile acid profile, and chronic low-grade inflammation related to obesity. However, the early temporal changes in these markers following LSG have not been well investigated. This study aimed to evaluate the early effects of LSG on adipocytokines, bile acid profile, and inflammatory markers. This was a nonrandomized prospective study examining morbidly obese Japanese patients undergoing LSG. Serial measurements of leptin, adiponectin, bile acids, fibroblast growth factor (FGF)-19, and inflammatory markers were performed preoperatively and 1 and 6 months after LSG. The study included ten patients (five females) with a mean age of 48.8 years and BMI 40.9 kg/m2. At baseline, 90% of the patients had T2DM, 70% had dyslipidemia, and 90% had hypertension. Patients lost 5.1 kg/m2 BMI at 1 month and 10.1 kg/m2 BMI at 6 months. The leptin levels sharply decreased, and FGF-19 increased significantly as early as 1 month postoperatively. Adiponectin levels showed an increasing trend at 1 month and a significant increase at 6 months. A significant decrease in high-sensitivity CRP and plasminogen activator inhibitor-1 was observed at 6 months. No significant changes were observed in interleukin (IL)-6, IL-8, tumor necrosis factor-α, serum amyloid A protein, or monocyte chemotactic protein-1 throughout the study. LSG improved the secretion of adipocytokines, increased FGF-19 secretion soon after surgery, and slowly ameliorated inflammation related to obesity through significant weight loss.

Because Bombyx mori ABC transporter C2 (BmABCC2) has 1000-fold higher potential than B. mori cadherin-like protein as a receptor for Bacillus thuringiensis Cry1Aa toxin (Tanaka et al., 2013), the gate-opening ability of the latent pore under six extracellular loops (ECLs) of BmABCC2 was expected to be the reason for its higher potential (Heckel, 2012). In this study, cell swelling assays in Sf9 cells showed that BmABCC2 mutants lacking substrate-excreting activity retained receptor activity, indicating that the gate-opening activity of BmABCC2 is not responsible for Cry1Aa toxicity. The analysis of 29 BmABCC2 mutants demonstrated that 770DYWL773 of ECL 4 comprise a putative binding site to Cry1Aa. This suggests that specific toxicity of Cry1Aa toxin to a restricted range of lepidopteran insects is dependent on conservation and variation in the amino acid residues around 770DYWL773 of ECL 4 in the ABCC2.

In this study, we examined insect and human ABCC transporters closely related to the lepidopteran ABC transporter C2 (ABCC2), a powerful receptor for the Bacillus thuringiensis Cry toxin, for their responses to various Cry toxins. ABCC2 and the lepidopteran ABC transporter C3 (ABCC3) conferred cultured cells with susceptibility to a lepidopteran-specific Cry1Aa toxin but not to lepidopteran-specific Cry1Ca and Cry1Da. One coleopteran ABCC transporter specifically responded to a coleopteran-specific Cry8Ca toxin. ABCC transporters from a dipteran insect and humans did not respond to any of the tested Cry toxins that are active to lepidopteran and coleopteran insects. These results yield important information for our understanding of insect specificity of Cry toxins and provide the first demonstration of a coleopteran ABCC transporter that serves as a Cry toxin receptor.

The incisional surgical site infection (SSI) is an extremely common complication following open abdominal surgery and imposes a considerable treatment and cost burden. We conducted a multicenter open-label randomized controlled trial at three Tokyo Metropolitan medical institutions. We enrolled adult patients who underwent either an elective or an emergency open laparotomy. Eligible patients were allocated preoperatively to undergo wound closure with either subcuticular sutures or staples. A central Web-based randomization tool was used to assign participants randomly by a permuted block sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to each group. The primary endpoint was the occurrence of a superficial SSI within 30 days after surgery in accordance with the Centers for Disease Control and Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 ( http://www.umin.ac.jp/ctr ). Between September 1, 2010 and August 31, 2015, 401 patients were enrolled and randomly assigned to either group. One hundred and ninety-nine patients were allocated to the subcuticular suture and 202 patients to the staple groups (hereafter the “suture” and “staple” group, respectively). Three hundred and ninety-nine were eligible for the primary endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201 staple patients. Overall, the rate of superficial SSIs did not differ significantly between the suture and staple groups. Subcuticular sutures did not increase the occurrence of superficial SSIs following open laparotomies mainly consisting of clean-contaminated surgical procedures. The applicability of the wound closure material and method is likely to depend on individual circumstances of the patient and surgical procedure.

Question: A previously healthy 39-year-old man presented to our hospital with a 1-week history of epigastric pain, nausea, and vomiting. He had no concomitant medical condition. His past medical history was unremarkable. He had no previous surgery or thoracoabdominal trauma history. The routine work-up on admission was normal. An immediate chest radiograph demonstrated the air–fluid level that projected above the diaphragm, to the far left of the midline (Figure A). The upper gastrointestinal (GI) series showed the esophagogastric unction was in the normal position, but the contrast medium would not pass through the mid-stomach (Figure B). The contour and orientation of the stomach by upper GI series and endoscopy suggested a mesenteroaxial gastric volvulus with herniation of the gastric body into the thorax (Figure C). Subsequent computed tomography of the chest and abdomen showed a diaphragmatic hernia containing he transverse colon as well as a significant portion of the posterior gastric body (Figure D). He elected to undergo a laparoscopic operation. he intraoperative finding is shown in Figure E (1, lower esophagus; 2, left paraesophageal space; 3, intervening muscle band; 4, left iaphragmatic crus; 5, lower lobe of the left lung through the defect). What is the diagnosis? Look on page 1623 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information n submitting your favorite image to Clinical Challenges and Images in GI.

We aimed at investigating the efficacy of multidetector computed tomography (MDCT) angiogram reconstructed using the maximum intensity projection (MIP) technique for the assessment of perigastric vascular anatomy before laparoscopy-assisted gastrectomy (LAG) for gastric cancer. Seventy-one patients who underwent LAG were enrolled in the study. Contrast-enhanced scans of the portal venous phase were performed by a MDCT scanner. The CT images were reconstructed using thin-slab MIP. The anatomic variations in the inflow and the location of the left gastric vein (LGV) were detected. The patterns of perigastric arterial origins were divided according to Michels' classification. The intraoperative blood loss on LAG was compared before and after MDCT angiography was introduced in the study. The LGV flowed into the portal vein in 31 patients; the splenic vein, 25 patients; and the junction of these two veins, 15 patients. The LGV passed to the dorsal and ventral sides of the common hepatic artery in 30 and 13 patients and to the dorsal and ventral sides of the splenic artery in 8 and 20 patients, respectively. Michels' type II was found in one patient; type V, in three patients; and type VI, in two patients. The LGV location detected by MDCT was confirmed during surgery in all cases. Intraoperative blood loss after introduction of the MDCT angiography was significantly less than that before its introduction (p = 0.0032). An MDCT angiogram reconstructed using the MIP technique is effective for assessing the perigastric vascular anatomy before LAG for gastric cancer.

胃小細胞癌は極めて稀で発育進展が速く予後不良な疾患である．今回比較的長期生存が得られている胃小細胞癌の2例を経験したので報告する．症例1:80歳女性．卵巣癌術後経過観察中，上部消化管内視鏡検査にて前庭部小弯後壁に2型腫瘍を認めた．生検で胃小細胞癌と診断し幽門側胃切除術+D1β郭清を施行．病理組織学的所見はpT2(SS)，ly2，v2，pm(-)，dm(-)，pN1(2/32:#4d，6)，fStageIIだった．症例2:57歳男性．健診で噴門部に潰瘍を伴う粘膜下腫瘍様の病変を認めた．生検で胃小細胞癌と診断し胃全摘術+D2郭清，脾臓胆嚢合併切除術を施行．病理組織学的所見はpT2(MP)，ly2，v1，pm(-)，dm(-)，pN1(1/17:#3)，fStageIIだった．当院における胃切除症例2,566例中胃小細胞癌は2例であり，頻度は0.08％だった．2例は共にfStageIIで術後補助化学療法を行わず現在まで無再発経過観察中（3年2カ月，2年7カ月）である．若干の文献的考察を加えて報告する．

This study aimed to determine the prognostic factors and the values that predict survival after percutaneous endoscopic gastrostomy (PEG) tube placement in patients with amyotrophic lateral sclerosis (ALS).We retrospectively analyzed the correlations for 97 consecutive patients with ALS between clinical parameters and survival following PEG tube placement using the log-rank test and Cox proportional-hazards models.The log-rank test showed that an arterial carbon dioxide pressure (PaCO2 ) of ≤ 40 mmHg (P = 0.0054), a forced vital capacity (FVC) of ≥ 38% of predicted (P = 0.0003), and bulbar-onset (P = 0.0121) were significantly associated with better post-PEG survival. Multivariate analysis showed that the FVC and PaCO2 were associated with better post-PEG survival (P = 0.0081 and P = 0.0265, respectively).PEG tube placement in ALS is recommended when FVC is ≥ 38% of predicted and when PaCO2 is normal. Muscle Nerve 54: 277-283, 2016.

previously healthy, 51-year-old woman was Areferred to our hospital because of a gastric tumor adjoining the esophagogastric junction (EGJ). This tumor was discovered incidentally by an upper gastrointestinal (GI) series in the course of her annual medical check-up. The patient’s history was unremarkable. Physical examination and laboratory work-up showed no abnormalities. An esophagogastroduodenoscopy showed a dark-red EGJ tumor and a black blot accompanied by gray pigmentation scattered over almost the entire esophagus (Figure A and B). An endoscopic biopsy of the lesions showed proliferation of atypical melanocytes, which were immunohistochemically positive for the melanoma-specific antigen HMB-45 (Figure C). Further investigation showed no evidence for other manifestations of the malignant melanoma or metastasis from an extra-GI melanoma into these lesions. Preoperative computed tomography found no local or systemic metastases. The patient underwent a radical surgical resection with gastric tube pull-up. She received no adjuvant therapy although postoperative pathology showed lymph node metastasis in the upper mediastinum. She has been free of recurrence now for 1 year. Microscopically, the EGJ tumor presented some features of a skip lesion because it spread in the direction of the proximal esophageal epithelium and distal gastric mucosa (Figure D, red lines, skip lesions; yellow arrowhead, EGJ). This intraepithelial extension consisting of melanoma cells and atypical melanocytes is called radial growth (Figure E, green arrows), which is a definitive characteristic of primary mucosal melanoma (PMM). Although the exact tumorigenesis was unclear, these

There are numerous observations confirming that microglia expressing major histocompatibility complex (MHC) class II molecules are associated with the central nervous system (CNS) in aging and pathological conditions. In this study, we investigated the distribution of MHC class II-positive microglia in Parkinson's disease (PD) brains. The number of MHC class II-positive microglia in the substantia nigra (SN) and putamen increased as the neuronal degeneration of the SN proceeded. These cells were also ICAM-1 (CD54) and LFA-1 (CD11a) positive. The number of activated microglia not only in the SN and putamen but also in the hippocampus, transentorhinal cortex, cingulate cortex and temporal cortex in PD was significantly higher than that in the normal control. Most activated microglia persisted regardless of the presence or absence of Lewy bodies. They were frequently associated not only with alpha-synuclein-positive Lewy neurites, but also with TH-16-positive dopaminergic and WH-3-positive serotonergic neurites, as well as MAP-2- and SMI-32-positive neurites. These activated microglia were also positive for TNF-alpha and interleukin-6, which are known to have a neuroprotective function. We conclude that MHC class II-positive microglia are a sensitive index of neuropathological change and are actively associated with damaged neurons and neurites.

4010 Background: Sb-PTX is a standard second-line treatment for patients (pts) with AGC. Nab-PTX was developed to avoid the toxicities with use of solvents in sb-PTX and potentially improve efficacy. Based on ABSOLUTE trial, we conducted the additional analysis to evaluate the efficacy and QOL of nab-PTX and sb-PTX. Methods: Pts who were refractory to a fluoropyrimidine-containing first-line treatment were randomly assigned (1:1:1) to receive intravenous q3w nab-PTX (260 mg/m2) on day 1 of a 21-day cycle, and q1w nab-PTX (100 mg/m2) or q1w sb-PTX (80 mg/m2) on days 1, 8, and 15 of a 28-day cycle. The primary objective was to evaluate whether q3w nab-PTX and q1w nab-PTX were non-inferior to q1w sb-PTX in terms of overall survival (OS). Tumor shrinkage at 8 weeks and at the time of the best response were also investigated. For the QOL analysis, EQ-5D score were collected at baseline and every 8 weeks during the first 24 weeks, and thereafter at every 24 weeks. Time to deterioration of EQ-5D score was compared between each arm as a minimally important difference of 0.05. Results: 741 pts were randomly assigned to q3w nab-PTX, q1w nab-PTX, or q1w sb-PTX. Median OS (months) were 10.3, 11.1, and 10.9, respectively. Q1w nab-PTX was non-inferior to q1w sb-PTX (hazard ratio 0.97, 97.5% CI 0.76-1.23; non-inferiority one-sided p = 0.0085), whereas q3w nab-PTX was not non-inferior to q1w sb-PTX (1.06, 95% CI 0.87-1.31; non-inferiority one-sided p = 0.062).The response rate of target lesions at 8 weeks and at the time of the best response (%) were 22.1 and 27.7 for q3w nab-PTX, 28.2 and 34.9 for q1w nab-PTX, and 18.0 and 25.6 for q1w sb-PTX. Median time to deterioration of EQ-5D score (months) were 2.1 in q3w nab-PTX, 3.8 in q1w nab-PTX, and 3.7 in q1w sb-PTX. Conclusions: Q1w nab-PTX was non-inferior to q1w sb-PTX in terms of OS. In addition, q1w nab-PTX showed favorable effect in comparison with q1w sb-PTX in terms of response rate of target lesions and time at best response. QOL was similar between q1w nab-PTX and q1w sb-PTX. These results suggest that q1w nab-PTX is a useful second-line treatment for pts with AGC. Clinical trial information: 132059.

Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles (NFTs) without senile plaques (SPs). In this study, we investigated the distribution of human leukocyte antigen (HLA)-DR-positive activated microglia in postmortem brain tissue of six patients with DNTC and six patients with Alzheimer disease (AD). HLA-DR-positive activated microglia were observed to associate with SPs in AD. In the DNTC brain, which lacks SPs, HLA-DR-positive microglia were mainly accumulated around weakly tau-positive NFTs, which were also positive for anti-amyloid-P and anti-C3d antibodies. The results of this study suggest that the complement pathway is also activated in the DNTC brain and that immune and inflammatory responses, including microglia activation, may occur around extracellular NFTs in DNTC patients.

The authors report an autopsy case characterized by progressive lethargy and autonomic failure with a distinctive pattern of occurrence of Lewy bodies. Autonomic dysfunction such as sleep apnea, orthostatic hypotension, dysuria, and hypohidrosis predominated with lethargy, whereas parkinsonism was not apparent. Numerous Lewy bodies were widely evident microscopically in brainstem nuclei and the intermediolateral cell columns of the spinal cord, as well as in the sympathetic ganglia, but were rare or absent in the cerebral cortex and other supratentorial structures. Marked neuronal loss was seen in the locus ceruleus, raphe nuclei, dorsal vagal nuclei, and intermediolateral cell columns, but neurons in the substantia nigra, other brain regions, and sympathetic ganglia appeared undiminished. This case represents a specific clinicopathologic form of Lewy body disease occurring predominantly in the brainstem, spinal cord, and sympathetic ganglia.

Carotid body tumor is a rare entity. No more than 70 cases of the disease have been reported in Japan so far. We succesfully performed a surgical therapy for a patient with carotid body tumor who was seen at the hospital because of a painless tumor on the neck. To make the definite diagnosis by preoperative imagins including CT and angiography and to select an appropriate operative procedure in accordince with local findings are determinant factors for the successful treatment of the disease.

Background Obesity is known to be a preoperative risk factor for gastric cancer surgery. However, the influence of obesity on laparoscopy-assisted distal gastrectomy (LADG) remains controversial. In the present study, we evaluated several obesity parameters and investigated the influence of obesity on the surgical outcomes of LADG for gastric cancer. Materials and methods Between January 2010 and July 2011, 84 patients who underwent LADG for gastric cancer were enrolled. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured in cross-sectional CT scan using SlimVision ® software. Patients were classified into two groups by the degree of BMI or VFA. Surgery time and blood loss were compared between each two groups. Predictive factors for perioperative complications were assessed by univariate and multivariate analyses. Results There were no significant differences in surgery time or blood loss between patients with high and low BMIs. In contrast, high VFA patients had significantly longer surgery times ( p =0.0047) and higher estimated blood loss ( p =0.0034) than low VFA patients. By univariate and multivariate analyses, only a high VFA significantly predicted perioperative complications ( p =0.0162, p =0.0288). Conclusions We suggest that VFA is more accurate than BMI in predicting surgery time, blood loss, and perioperative complications associated with LADG for gastric cancer. The visceral fat area could be efficiently assessed before laparoscopic surgery for gastric cancer in obese patients.

1.1 What is Parkinson’s disease Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD). PD is characterized by degeneration and cell death in dopaminergic neurons in the substantia nigra pars compacta (SNpc) and loss of their nerve terminals in the striatum (putamen and caudate nucleus), accompanied by the depletion of the neurotransmitter dopamine (DA) in the striatum. This depletion causes motor symptoms, i.e., resting tremor, muscle rigidity, and akinesia. The level of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine (DA, noradrenaline, and adrenaline) synthase in the nigro-striatal region of PD patients is decreased (Nagatsu and Sawada M., 2007). A small percentage of PD is familial with a hereditary history. However, most cases of PD (approximately 90-95 %) are sporadic without any hereditary history. In 2009, 16 causative genes of familial PD have been identified (Satake et al., 2009), including PARK1 (αsynuclein), PARK2 (parkin), PARK4 (α-synuclein), PARK5 (UCHL-1), PARK6 (PINK1), PARK7 (DJ-1), PARK8 (LRRK2), and PARK9 (ATP13A2). Sporadic PD and some cases of familial PD are characterized by the presence of cytoplasmic inclusions named Lewy bodies, which consist mainly of α-synuclein protein, the product of the PARK1 gene. α-Synuclein is observed not only in PD but also in various neurodegenerative diseases, such as dementia with Lewy bodies (DLB). Based on their investigation of the distribution of α-synuclein-positive Lewy bodies and Lewy neurites in PD patients, Braak et al. (2003) proposed a hypothesis that the pathological process of PD starts first from the lower brain stem and then spreads to the midbrain, limbic system, and cerebral cortex. α-Synuclein-positive inclusions are observed in the anterior olfactory nucleus, dorsal motor nucleus of vagus nerves, and also in peripheral autonomic neurons including those of the sympathetic ganglia, adrenal medulla, and intestinal Auerbach’s plexus. Braak et al. (2003) proposed that symptoms of PD appears when Lewy bodies are formed in dopaminergic neurons in the substantia nigra (SN) .

To help understand effector mechanisms in experimental allergic encephalomyelitis (EAE) we examined the effects of adding ‘irrelevant’ lymphocytes from non-EAE donors to major basic protein (MBP)-reactive lymphocytes in the adoptive transfer of EAE (Tr-EAE). The intravenous injection of tentanus toxoid-reactive lymphocytes (TT-cells) and phytohemagglutinin-stimulated lymphocytes on the same day or 2 days after intra-arterial injection of MBP-reactive lymphocytes enhanced the clinical and pathological expression of Tr-EAE. In lymphocyte trafficking studies there was significant accumulation of these injected TT-cells in the central nervous system during enhanced transfer of EAE. W3/25-positive cells were much more predominant in lesion of central nervous system when reinjected with TT cells along with MBP cells compared with lesions of rats injected with MBP cells alone. These findings suggest possible participation of lymphocytes other than MBP-reactive cells in the expression of EAE and provide a useful model to further explore effector mechanism in the future.

We compared the relationship between regional cerebral blood flow (rCBF) of the olfactory area and the cognitive function and anosmia in patient with Parkinson disease (PD) and in those with Alzheimer disease (AD). UPDRS III, MMSE, HDS-R, CDR, Beck Depression Inventory (BDI) were employed in this study. The subjects included 56 PD patients (average age 71.4+/-9.69 years), 23 AD patients (average age 73.3+/-7.12 years), 12 patients with mild cognitive impairment (MCI) (average age 72.5+/-6.89 years), and 9 age-matched controls (NC) (average age 73.8+/-6.61 years). Next we intravenously injected 1 ampule of thiamine propyldisulphide (Alinamin) and confirmed anosmia. In addition, we performed 123I-IMP SPECT (SEE methods) and satistically determined rCBF of the olfactory area based on the basis of the Z scores of the interest area. Anosima was detected in approximately 40% of the PD and AD patients. The HDS-R and MMSE scores were significantly higher in patients with anosima than in those without anosima; the CDR scores were significantly higher in the former than in the latter. Further, the incidence of anosima in PD patients and AD patients with MCI increased with an increase in the CDR scores. In order to determine the rCBF of the olfactory area of the PD and AD patients. As to rCBF of the olfactory area, we examined left and right Z scores of hippocampus, parahippocampus, amygdala, and uncus at Talairach level 3 and the scores of the Brodmann area 28, 34, 35, and 36 at Talairach level 5. In patients with anosmia, the Z scores were significantly high in cases with anosmia in all areas except the right Brodmann area 34 in PD patients and the right Brodmann area 28 and bilateral the Brodmann area 34 of both sides in AD patients. Some parts of the olfactory area are closely related to cognitive function, and it appeares that a reduced rCBF in the olfactory areas may lead to a functional decline in these regions which may cause anosmia and cognitive decline in PD and AD patients.