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BACKGROUND/AIM This study examined the prognostic impact of the past history of breast cancer screening within the last 2 years (PH-BCS), for patients with triple negative breast cancer (TNBC), a subtype that carries extremely poor prognosis. PATIENTS AND METHODS Eighty-six consecutive cases with TNBC, who underwent surgery at our faculty from 2009 to 2015, were divided into two groups according to PH-BCS. Prognostic analyses for disease-free survival and overall survival between the two groups were performed. RESULTS The positive PH-BCS group (n=44) had a significantly better prognoses than the negative PH-BCS group (n=42) (p

Background/aim Several studies have reported that DM is closely associated with an increased incidence of hepatocellular carcinoma (HCC). To clarify the effects of diabetes mellitus (DM) and antidiabetic medications on the prognosis of patients with non-B non-C (NBNC) HCC following curative initial hepatectomy. Patients and methods HCC patients (n=156) were divided into three groups according to the presence or absence of chronic viral hepatitis: hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and NBNC group. The clinical characteristics and survival outcomes were compared. In the NBNC group, univariate and multivariate analyses were conducted to determine prognostic factors. Results The NBNC group had a higher incidence of DM, ethanol intake, and large nodules than the other groups. Disease-free survival (DFS) was significantly worse in the NBNC group than in the HBV group. In the NBNC group, insulin treatment was an independent prognostic factor for DFS and overall survival (OS). Conclusion Medications for DM that affect insulin resistance might be appropriate prognostic factors for NBNC-HCC.

BACKGROUND/AIM Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development. PATIENTS AND METHODS A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated. RESULTS The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p

Background Nodular fasciitis (NF) is a type of rare and rapidly growing tumor that affects the muscular fascial layers. Due to its locally aggressive nature and rapid growth, NF can be mistaken as a malignant process on either clinical or histological grounds. Case presentation A 61-year-old man was affected by rectal cancer. We performed a robotic, high-anterior resection with lymph node dissection. According to the 8th edition of Union for International Cancer Control, the diagnosis was stage I pT2N0M0. During a routine follow-up 1.5 years after the robotic surgery, a computed tomography examination revealed a tumor in the upper right abdominal wall, at the site of the surgical port, that measured 45 mm. Magnetic resonance imaging indicated a hypo-intensive mass within the right straight muscle of the abdomen. Port site recurrence following the robotic surgery for rectal cancer was suspected, and an ultrasound-guided fine-needle aspiration was performed; it revealed a low-grade myofibroblastic tumor or benign neoplasm, but was inconclusive. We performed an excision of the lesion, and histopathology confirmed NF, seen as a solid, nodular, spindle-cell lesion. The patient was postoperatively followed for more than 1 year without any sign of recurrence of either cancer or NF. Conclusions NF is histologically benign, but local recurrence frequently occurs. We encountered a patient with NF at the port site after robotic surgery for rectal cancer.

Behçet’s disease (BD) is a multisystem inflammatory disease of unknown origin. Rarely, BD occurs together with myelodysplastic syndrome (MDS). Interestingly, it is speculated that these are not simple coexistence but that the etiology of intestinal BD is at least partly derived from MDS itself. Furthermore, there is a relationship between MDS in patients with intestinal BD and trisomy 8. Immunosuppressive agents alone are insufficient to control MDS-associated BD, and many of these patients die of infection or hemorrhage. Surgery is considered for intestinal BD patients who are unresponsive to medical treatment or those with bowel complications such as perforation or persistent bleeding. We report a case of intestinal BD associated with MDS and trisomy 8. The patient was unresponsive to oral steroids and immunosuppressive treatment; the patient improved by surgical repair of a bowel perforation. Five years after the surgery, the patient is free of recurrence and not on medication. Our experience suggests that surgery may provide an effective therapeutic option for the treatment of MDS-related BD.

Tissue biopsies are the gold-standard for investigating the molecular characterization of tumors. However, a "solid" biopsy is an invasive procedure that cannot capture real-time tumor dynamics and may yield inaccurate information because of intratumoral heterogeneity. In this review, we summarize the current state of knowledge about surgical treatment-associated "liquid" biopsy for patients with digestive organ tumors. A liquid biopsy is a technique involving the sampling and testing of non-solid biological materials, including blood, urine, saliva, and ascites. Previous studies have reported the potential value of blood-based biomarkers, circulating tumor cells, and cell-free nucleic acids as facilitators of cancer treatment. The applications of a liquid biopsy in a cancer treatment setting include screening and early diagnosis, prognostication, and outcome and recurrence monitoring of cancer. This technique has also been suggested as a useful tool in personalized medicine. The transition to precision medicine is still in its early stages. Soon, however, liquid biopsy is likely to form the basis of patient selection for molecular targeted therapies, predictions regarding chemotherapy sensitivity, and real-time evaluations of therapeutic effects.

Objectives: Rectal stump washout has been widely performed to prevent the implantation of exfoliated cancer cells (ECCs) in patients with rectal cancer. However, it remains unclear whether intraluminal washout before transection is required in patients with sigmoid colon cancer. Therefore, this pilot study was conducted to elucidate the necessity of intraluminal washout for sigmoid colon cancer patients in comparison with rectal cancer patients by cytological assessments. Methods: A total of 16 patients with sigmoid colon cancer and 24 patients with rectal cancer who underwent sigmoidectomy or anterior resection with anastomosis using double-stapling technique were enrolled. A transanal washout sample was collected before washout and after irrigation with 500 and 1,000 mL of saline. Cytological assessments were conducted according to the Papanicolaou classification, and class IV and V cells were defined as malignant. Results: Before washout, exfoliated cancer cells were found in 15 of 24 (62.5%) patients with rectal cancer and in 1 of 16 (6.2%) patients with sigmoid colon cancer (p < 0.001). Distal-free margin from the tumor was significantly shorter in patients with cancer cells (p = 0.002), and the length of the distal-free margin was significantly associated with the tumor location. After irrigation with 500 and 1,000 mL of saline, no cancer cell was found in all patients with sigmoid colon cancer, whereas ECCs were still found in five patients with rectal cancer (20.8%). Conclusions: Intraluminal washout with 1,000 mL may be sufficient for sigmoid colon cancer patients with longer distal-free margin. A large-scale, randomized controlled study is necessary to confirm these results.

BACKGROUND/AIM Elevated neutrophil-lymphocyte ratio (NLR) has been reported to be a poor prognostic factor in patients with colorectal cancer (CRC). However, no studies have focused on the dynamic change of preoperative NLR (pre-NLR) in CRC patients. We investigated the prognostic value of the change in NLR (ΔNLR) in CRC patients before and after surgery. PATIENTS AND METHODS We retrospectively analyzed the data from 307 patients with stage II or III CRC. We compared the clinicopathological factors, OS, and DFS among the various NLR factors. RESULTS The 5-year OS rate of the high ΔNLR group was significantly lower than that of the low ΔNLR group (p

Postoperative complications have been recognized to have an adverse prognostic impact in various types of cancer. However, in a recent study, it has been reported that postoperative complications of total gastrectomy with splenectomy have little impact on the long-term outcomes of patients with gastric cancer. In addition, the mechanisms underlying the effect of postoperative complications on outcomes remain to be elucidated. We hypothesized that immunosuppression by postoperative complications may affect long-term outcomes in patients with esophageal cancer. In this retrospective study, we assessed in 153 patients with esophageal cancer who underwent curative subtotal esophagectomy at our hospital and examined the correlation between postoperative complications, and multiple clinicopathological factors, and long-term outcomes with the patients stratified by total lymphocyte count (TLC). The median preoperative TLC was 1432. A total of 115 patients (75.2%) had a TLC of ≥ 1000/μL (high TLC group), and the remaining 38 patients (24.8%) had a TLC of

Background/aim The high rate of recurrence and repetitive features of hepatocellular carcinoma (HCC) require specific treatment strategies. This study aimed to evaluate the long-term outcomes of recurrent HCC focusing on clinicopathological factors. Patients and methods A total of 104 patients who were treated with re-hepatectomy, radiofrequency ablation (RFA) or transcatheter arterial chemoembolization for recurrent HCC were analyzed. Post-recurrent prognoses were compared between each treatment group based on the presence of adverse prognostic factors (APFs) identified. Results In the hepatectomy group, the prognosis of patients with APFs was significantly worse compared to those without APFs. By contrast, the survival rate of patients who underwent RFA was not significantly different from those with and without APFs. Conclusion Our results demonstrate the heterogeneity that exists in terms of the long-term survival of patients with recurrent HCC. The treatment strategy for recurrent HCC should be based on the assessment of presence of APFs to improve long-term prognosis.

Background/aim The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. Patients and methods Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. Results Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. Conclusion PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.

Gastric cancers located within the upper-third of the stomach (UGC), especially the esophagogastric junction GC (EGJGC), have distinct clinicopathological features due to their potential for multidirectional lymphatic spread. In this study, we investigated the clinical significance of hiatal hernias (HH) in patients with UGC, including EGJGC. In this retrospective study, we assessed status of HH in 147 patients with UGC who underwent curative resection at our hospital and examined the correlation between the presence of HH (+) and multiple clinicopathological factors. Thirty-four patients (23%) were HH (+). However, we found no significant correlation between HH (+) and clinicopathological factors. HH (+) patients frequently developed lymph node recurrences. Prognosis was significantly better in patients with UGC and HH (−), compared to those with UGC and HH (+). Similarly, EGJGC patients who were HH (−) showed superior survival compared to HH (+) patients. Multivariate analysis found that the HH (+) (p = 0.004), histological type (p = 0.029), and nodal stage (p = 0.034) were independent prognostic factors. The presence of HH might affect lymphatic spread of tumor cells, and consequently prognosis of patients with UGC. Therefore, special attention is needed in developing surgical and postoperative strategies for such patients with UGC who are HH (+).

Background The low accuracy of preoperative diagnosis of lymph node metastasis in gastric cancer (GC) complicates decisions on patient indication for neoadjuvant chemotherapy. Methods We investigated the use of preoperative clinical diagnosis of lymph node involvement (cN) in GC patients compared with postoperative pathological diagnosis. Results In a series of 265 patients enrolled at the University of Yamanashi Hospital, the overall sensitivity was 44.4% and specificity was 93.4% of CT for detecting lymph node metastasis. The positive and negative predictive values were 80.0% and 73.8%, respectively. The negative predictive value was lower for undifferentiated adenocarcinoma than that for differentiated adenocarcinoma (64.9% vs. 78.7%, p = 0.034). In cT2 ≤ and cN2 ≤ GC, overdiagnosis of lymph node metastasis was significantly more frequent in patients with differentiated (50.0%) than in undifferentiated (13.3%) adenocarcinoma (p = 0.046). Conclusions Diagnostic accuracy of lymph node involvement depended on histological type and cT-stage. Thus, considering preoperative histological type in GC, it may be useful to decide treatment plan.

BACKGROUND/AIM Treatment algorithms for primary and recurrent hepatocellular carcinoma (HCC) are described in the current Japanese Clinical Practice Guidelines; however, primary and recurrent tumors exhibit several differences in oncological characteristics such as clinicopathological features and prognostic factors. This study aimed to investigate the prognostic factors for recurrent HCC including time of recurrence after primary hepatectomy, to elucidate appropriate treatment strategies in these patients. PATIENTS AND METHODS One hundred and nine patients who had undergone radical resection of primary HCC at our Hospital and had experienced intrahepatic recurrence were included in this study. Patients were categorized into the early-recurrence (ER

Background/aim The extent of lymph node (LN) dissection is defined according to the type of gastrectomy regardless of tumor location in recent Japanese gastric cancer treatment guidelines. However, lymphatic flow from lower-third stomach mainly drain to supra- and infra-pyloric nodes, as well as to partially lesser curvature nodes along the descending limb of the left gastric artery. In this study, we evaluated the prognostic impact of LN dissection of right paracardial (No. 1) and left greater curvature (No. 4sb) nodes in gastric cancer of lower-third stomach (LGC). Patients and methods A total of 239 patients with LGC who underwent distal gastrectomy at our hospital were retrospectively analyzed. The therapeutic value index (TVI) of each node was calculated by multiplying the incidence of LN metastasis by the 5-year survival rate of patients with metastasis to each nodal station. Results The incidence of No. 1 LN metastasis was 4.5% (positive/negative; 5/110 cases, unknown or no description; 129 cases). The 5-year survival rate of patients with metastasis to the node was 0%, and consequently the TVI of No. 1 LN station was "0". Similarly, the TVI of No. 4sb was found to be "0". Conclusion Survival benefit of dissection of No. 1 and No. 4sb LNs was presumed to be extremely low, suggesting that dissection of these two LNs could be omitted in LGC patients when undergoing distal gastrectomy.

Background/aim Although perioperative management and operative techniques for pancreatic surgery have improved, postoperative pancreatic fistula (POPF) remains the major cause of morbidity and mortality following distal pancreatectomy (DP). The purpose of this study was to evaluate the superiority of the reinforced stapler compared to the bare triple row stapler. Patients and methods A total of 93 patients who underwent DP at the First Department of Surgery at Yamanashi University were examined. The patients were divided into two groups according to the closure method for the pancreatic stump; the bare triple-row stapler (BTRS) group and the reinforced triple-row stapler (RTRS) group. The postoperative outcomes were then compared in terms of several clinicopathological factors between the two groups. Results Seven patients were diagnosed with Grade B/C POPF in this series. The incidence of POPF in the RTRS group was lower than that in the BTRS group (3.6% vs. 13.5%), although there was no significant difference (p=0.077). Further detailed analysis demonstrated that RTRS significantly reduced POPF compared to BTRS in obese patients with a BMI >25.0 kg/m2 (p=0.038). Conclusion Reinforced triple-row staplers may reduce the incidence of severe POPF, especially in obese patients with a BMI >25 kg/m2.

Background/aim Nab-paclitaxel plus gemcitabine (nab-P+Gem) is one of most reliable and effective regimens for borderline or unresectable pancreatic cancer (PC). However, the feasibility and clinical benefits of this regimen have never been evaluated for patients with recurrent PC after pancreatectomy. The aim of this study was to investigate the feasibility of combination therapy with nab-paclitaxel plus gemcitabine (nab-P+Gem) for patients with recurrent PC. Patients and methods Twenty-two patients with recurrent PC received an intravenous infusion of nab-P (125 mg/m2) and Gem (1,000 mg/m2) on days 1, 8, and 15 of a 4-week cycle. The primary end-point of this study was completion of the 4 cycles. The secondary end-points were the safety, efficacy, and disease control rate. Results The treatment completion rate of the 4 cycles was 90.9%. The objective response rate was 13.6% and the disease control rate was 63.6%. The median progression-free survival was 7.2 months. The most common grade 3 or higher hematological toxicity was neutropenia (72.7%). There was no treatment-related death. Furthermore, the chemotherapeutic effects varied with the time of recurrence. Conclusion Combination nab-P+Gem therapy was well-tolerated and effective in patients with recurrent PC.

Background Traditionally, the surgery for simultaneous double cancer of the stomach and colon required a large incision to the upper and lower region of the abdomen. In this case, an artificial blood vessel was located under the skin after revascularization. Considering ischemia due to graft compression by incision retractor during laparotomy, this was difficult to do. This is a report on laparoscopic surgery for simultaneous double cancer of the stomach and colon after revascularization. Case presentation A 69-year-old man had early gastric cancer and advanced sigmoid colon cancer. He had suffered from thromboangitis obliterans and has undergone revascularization many times due to poor blood flow in his lower limbs. He had had some artificial blood vessels inserted under the skin, confirmed by blood vessel construction image by preoperative computed tomography (CT). There was a bypass vessel from the left axillary artery to the left femoral artery under the skin of the left thoracoabdominal. In addition, there were two bypass vessels from the left external iliac artery to the right femoral artery under the skin of the lower abdomen. One of the two bypasses was occluded. In the blood flow to the intestinal tract, the inferior mesenteric artery was already occluded. Peripheral blood flow in the common iliac artery depended on blood flow from the artificial blood vessel, and blood flow from the internal iliac artery to the rectum was poor. Laparoscopic Hartmann’s operation was performed for Stage II B (UICC 8th Edition) sigmoid colon cancer. Because the blood flow in the intestinal tract on the anal side was poor, we thought that anastomosis was at a high risk for leakage. Laparoscopic total gastrectomy was also performed simultaneously for two Stage I (UICC 8th edition) gastric cancers in the cardia and body. The location of the port site and stoma was carefully determined preoperatively to prevent damage and infection to the artificial blood vessels. Minimal invasive surgery was performed using laparoscopic surgery. Conclusions Laparoscopic surgery with small incisions is useful for patients with double cancer who need an approach to the upper and lower abdomen. Furthermore, laparoscopic surgery has less interference on graft in patients with artificial blood vessels under the skin by intraperitoneal approach.

Pancreatectomy is a highly invasive procedure with extensive intraoperative blood loss (IBL) and high risk of postoperative pancreatic fistula (POPF). We conducted an experimental and retrospective clinical study to determine whether the malignant behaviors of pancreatic cancer cells were enhanced by exposure to blood components in vitro and to evaluate the oncological significance of high IBL and POPF in pancreatic cancer. This study included 107 patients undergoing radical pancreatectomy in the University of Yamanashi Hospital between 2011 and 2017, classified into high (n = 29) and low (n = 78) IBL groups. In vitro experiments included functional analyses of Panc-1 pancreatic cancer and normal mesothelial cells exposed to patient blood components, and clinical data were used to assess the contribution of IBL and POPF to patient outcomes. The migration (p = 0.007), invasion (p < 0.001), and proliferation (p < 0.01) of Panc-1 cells were enhanced with platelet coculture. The ability of Panc-1 cells to adhere mesothelial cells was enhanced by plasma coincubation, especially in the presence of inflammation (p < 0.001). High IBL was associated with worse overall survival (p = 0.007) and increased locoregional recurrence (p = 0.003) in patients. POPF enhanced the negative prognostic significance of high IBL (p < 0.001 for overall survival, p = 0.001 for locoregional recurrence), indicating the oncological negative effects of high IBL and POPF. Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

Background Disseminated intravascular coagulation (DIC) is associated with high mortality in patients with severe sepsis. The purpose of this study was to investigate the effects of recombinant human thrombomodulin (rhTM) in septic patients undergoing continuous hemodiafiltration (CHDF). Furthermore, effects of rhTM in acute lung injury, the first target organ in sepsis, was investigated using a sepsis model in rats. Methods Clinical laboratory data, and the DIC, Sequential Organ Failure Assessment (SOFA), and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were compared between patients undergoing CHDF alone (rhTM- group; n = 23 cases) and patients undergoing CHDF treated with rhTM (rhTM+ group; n = 21 cases). Rats underwent cecal ligation and puncture (CLP) treated with or without rhTM, and acute lung injury (ALI) was analyzed. Production of TNF-α by isolated tissue macrophages (Mfs) was assessed. Results The numbers of leukocytes, and C-reactive protein and D-dimer levels were significantly suppressed, and platelet counts recovered significantly faster in the rhTM+ group compared with the rhTM- group. The DIC score was reduced in both groups. The SOFA and APACHE II scores gradually reduced in the rhTM+ group. The CHDF treatment and ICU admission periods were shortened in the rhTM+ group compared with the rhTM- group. Treatment of rhTM was an independent factor for CHDF treatment period by multivariate analyses. CLP-induced ALI was significantly improved by rhTM. Increased TNF-α production by tissue Mfs was significantly suppressed by rhTM in vivo and in vitro. Conclusion Additive effects of rhTM treatment were observed in septic patients undergoing CHDF.

The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Patients with lymph node tumors

BACKGROUND/AIM We aimed to evaluate the correlation between stroke volume variation (SVV) and intraoperative blood loss (IBL) in hepatocellular carcinoma (HCC) resection and examine the perioperative utility of SVV-based management. PATIENTS AND METHODS Ninety-five patients who underwent partial or sub-segmental hepatectomy for HCC between 2013 and 2019 at the University of Yamanashi Hospital were retrospectively analyzed. A correlation analysis between IBL and SVV was performed, and then all cases were divided into three groups: high, middle, and low-SVV groups. Perioperative short-term outcomes based on SVV groups were analyzed. RESULTS There was a weak but significant negative correlation between SVV and IBL (ρ=-0.372, p

Background Postoperative pancreatic fistula (POPF) is one of the most serious complications after pancreaticoduodenectomy (PD). Various factors have been reported as POPF risks, but the most serious of these is soft pancreas. To reduce POPF occurrences, many changes to the PD process have been proposed. This study evaluates short-term results of anastomosis technique for PD. Methods In total, 123 patients with soft pancreases who had undergone PD at Yamanashi University between January 2012 and August 2020 were retrospectively analyzed. We divided these patients into two groups depending on the time PD was performed: a conventional group (n = 67) and a modified group (n = 56). Results The rate of clinically relevant POPF was significantly lower in the modified group than that in the conventional group (5.4% vs 22.4%, p value p value = 0.002). Conclusions Our novel anastomosis technique for pancreatojejunostomy reduced POPF in PD, especially in cases where the patient had a soft pancreas.

BackgroundThe indications for extrahepatic bile duct (EHBD) resection remain a major controversy in the surgical management of patients with gallbladder cancer. On the other hand, perineural invasion (PNI) was reported as an important factor in patients with gallbladder cancer because gallbladder cancer cells frequently spread to the tissues surrounding the EHBD via perineural routes. We assessed the correlation of PNI with clinicopathological factors in patients with gallbladder cancer to elucidate EHBD resection indications specifically in patients with PNI.MethodsThis retrospective study assessed the PNI status of 50 patients with gallbladder cancer who underwent curative resection and examined the correlation between the presence of PNI and clinicopathological factors.ResultsThirteen patients (26%) were PNI positive. PNI was significantly correlated with male sex, proximal-type tumor, lymphatic and vascular invasion, and advanced T stage. Multivariate analysis found that PNI positivity (p< 0.001), lymphatic invasion (p= 0.007), and nodal stage (p< 0.001) were independent prognostic factors. PNI was never observed in patients with stage T1 cancer. Conversely, PNI was detected rarely in distal-type tumors, all of whom developed various types of recurrences.ConclusionsThese results clearly demonstrated the prognostic impact of PNI in patients with gallbladder cancer. We suggest that EHBD resection in combination with cholecystectomy may not be useful for distal-type tumors from a perspective of PNI.

Highlights • Gastric duplication cyst(GDC) contiguous with the stomach and pancreatic tail is extremely rare. • GDCs are usually diagnosed at a younger age. In adults, they are very rare disease and the diagnosis may be difficult. • Surgical resection is considered to be the best treatment due to the difficulty of diagnosis. • Laparoscopic surgery is less invasive and should be selected whenever possible., Introduction Gastrointestinal duplication cyst is a congenital rare disease that may occur in any region from mouth to anus. Among them, gastric duplication cysts are very rare. Case report Here we report A 23-year-old Japanese man who visited our hospital to evaluate an abdominal tumor. Abdominal computed tomography showed a well-circumscribed homogenous low-density mass measuring 6.2 × 6.0 cm between the pancreatic tail and the upper posterior wall on the gastric greater curvature, and the mass seemed to originate from the pancreatic tail. We found intraoperatively that the mass adhered to the stomach and pancreatic tail strongly, so we performed laparoscopic partial gastrectomy and spleen-preserving distal pancreatectomy. Pathological findings showed that the lining epithelium of the cystic mass consisted of the gastric foveolar epithelium with fundic glands. Furthermore, the pancreatic tissue of the pancreatic tail and the muscular layer of the cystic mass were intermingled. Discussion GDCs are usually diagnosed at a younger age and in adults, they are very rare. Therefore, surgical resection is considered to be the best treatment due to the difficulty of diagnosis, and also that it mimics a pancreatic cystic tumor, and malignant transformation. Complete resection of the cyst is the ideal technique and laparoscopic surgery should be selected whenever possible. Conclusion We experienced a case of GDC continuous to both stomach and pancreatic tail. Laparoscopic surgery is safety and useful even if GDC is continuous with both the stomach and the pancreas.

Objectives Nutritional status significantly influences postoperative prognosis in gastrointestinal cancers. It has been evaluated using sarcopenia before treatments such as surgery and chemotherapy, despite constant changes in nutritional status. We consider that nutritional status at cancer recurrence is one of the important factors that affect treatment choice and intensity. This study evaluated the prognostic effects of improved postoperative nutritional status for people with colorectal cancer recurrence. Methods We enrolled 209 participants with pathologically confirmed stage II or III colorectal cancer who underwent radical resection. Sarcopenia was diagnosed using the psoas muscle index obtained from analysis of three-dimensional computed tomographic images. We adopted the cutoff value that was proposed by Hamaguchi et al. (psoas muscle index Results Among the 209 participants, 81 (38.8%) had preoperative sarcopenia; this group had significantly lower overall survival than those without sarcopenia (P = 0.028). Colorectal cancer recurred in 48 participants. Of those 46, sarcopenia was evaluated at the time of recurrence; 19 of those 46 had preoperative sarcopenia. Preoperative sarcopenia did not affect the cancer recurrence ratio (sarcopenia, 23.5%; non-sarcopenia, 21.3%; P = 0.893). The sarcopenia-improvement group had higher overall survival than the sarcopenia-continuation group (P = 0.042). Conclusions Among participants with preoperative sarcopenia, the prognosis at the time of recurrence improved for the sarcopenia-improvement group compared to the sarcopenia-continuation group. In people with colorectal cancer and sarcopenia, nutritional management is important not only before but also after surgery.

Cholestatic liver injury leads to liver dysfunction. The available evidence suggests that platelets can either promote or reduce liver injury and fibrosis. This study focused on the functions of the C-type lectin-like receptor 2 (CLEC-2), a new special platelet receptor that binds with podoplanin-activating platelets. The role of CLEC-2 and podoplanin in cholestatic liver injury was investigated. Mice were injected intraperitoneally with weekly doses of anti-CLEC-2 antibody (2A2B10) to achieve effective CLEC-2 inhibition in their platelets. Next, left and middle hepatic bile duct ligation (BDL) procedures were performed, and mice were euthanized 1 week later (2A2B10-BDL group). In addition, mice were prepared for control groups, and relevant histological and laboratory variables were compared among these groups. The inhibition of CLEC-2 resulted in increasing hepatocellular necrosis, hepatic inflammation, and liver fibrosis. In addition, podoplanin was strongly expressed in hepatic sinusoidal endothelial cells in BDL-treated mice. Moreover, in 2A2B10-BDL mice, total plasma bile acid levels were significantly increased. In summary, podoplanin is expressed on hepatic sinusoidal endothelial cells upon BDL. Platelets bind with podoplanin via CLEC-2 and become activated. As a result, the total bile acid pool is decreased. Therefore, the CLEC-2-podoplanin interaction promotes liver protection and inhibits liver fibrosis after cholestatic liver injury.

Background and purpose Approximately 20% of all patients with colorectal cancer (CRC) are diagnosed at more advanced stages with synchronous distant metastasis, and the prognosis in these patients is usually poor. The aim of this study was to determine the factors that can identify subgroup(s) of patients with stage IV CRC who could benefit from curative (R0) resection of both primary and metastatic lesions. Patients and methods A total of 126 patients with stage IV CRC who underwent surgical resection of primary tumor were retrospectively analyzed. Among these patients, 26 cases of R0 resection were further examined subsequently. Information on various clinicopathological factors of the patients were obtained from hospital records. Overall survival was estimated using the Kaplan-Meier method, and log-rank tests were used to compare survival distribution. All the factors with P

Polymorphisms of interleukin-1 (IL-1) genes have been reported to modify the risk of gastric carcinoma (GC) in Caucasians. The significance of IL-1β gene polymorphisms was evaluated in Japanese GC patients with or without infection of Helicobacter pylori and Epstein Barr virus (EBV) with special reference to the topographic features of GC. IL-1β gene polymorphisms at positions -511 and +3953 were evaluated by PCR-RFLP and a penta-allelic polymorphism of IL-1RA by PCR in healthy controls (n = 103) and GC (n =140; corpus 95, antrum 45). EBV-infection was determined in the neoplastic tissues by EBER1 in situ hybridization, and H. pylori infection in nonneoplastic gastric mucosa by PCR targeting of the H. pylori urease A gene. GC consisted of EBV-associated (n = 24) and EBV-negative (n = 116) patients, whereas H. pylori infection was positive in 130 cases. Among IL-1β gene polymorphisms, genotype IL-1β+3953 C/T was more frequent in the EBV-negative (21%) and corpus GC (23%) patients, compared to the controls (10%), respectively, although there was no genotype IL-1β+3953 T/T in either group. Thus, the effect of IL-1β+3953 T was statistically significant in logistic regression models adjusted for age in EBV negativity (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.02–5.05) and in the corpus GC (2.70, 1.19–6.12) with highest OR 3.55 (1.54–8.23) in EBV-negative corpus GC. There was no significant influence of IL-1 gene polymorphism in EBV-associated GC, but it occurred predominantly in the corpus (24/24) compared to EBV-negative GC (71/116) (p = 0.00002). There was no correlation between H. pylori infection and IL-1 gene polymorphism in GC. The cancer risk of the gastric corpus in Japanese is influenced by IL-1β+3953 polymorphisms. On the other hand, the risk of EBV-associated GC, which occurs predominantly in the corpus, is not influenced by this pro-inflammatory polymorphism. © 2005 Wiley-Liss, Inc.

We investigated the possible role of amiloride-sensitive ion channels of the ENaC/DEGenerin superfamily in the activation of trigeminal nociceptive neurons elicited by noxious chemical stimulation of the oral mucosa using two methodologies, single-unit recording and c-fos immunohistochemistry. In pentobarbital-anesthetized rats, single-unit recordings were made from neurons in superficial laminae of dorsomedial trigeminal subnucleus caudalis (Vc) that responded to noxious thermal and chemical stimuli applied to the dorsal tongue. Successive application of each of three chemicals (250 mM pentanoic acid, n=6 units; 250 mM citric acid, n=8; 5 M NaCl, n=6) evoked responses that were not affected following topical application of amiloride (1 mM). In separate experiments, pentobarbital-anesthetized rats received one of the following stimuli delivered to the dorsal tongue: 250 mM pentanoic acid (n=6); 1 mM amiloride followed by 250 mM pentanoic (N=6); 5 M NaCl (n=5); or 1 mM amiloride followed by 5 M NaCl (n=5). Two hours later they were perfused with 4% paraformaldehyde and the brain stems processed for c-fos immunoreactivity. Both pentanoic acid and 5 M NaCl evoked similar numbers and patterns of fos-like immunoreactivity (FLI) in dorsomedial Vc and other brain stem regions, with no significant difference in counts of FLI in animals pretreated with amiloride. These results suggest that amiloride-sensitive Na(+) channels are not essential in mediating the activation of intraoral trigeminal nociceptors.

In human studies, repeated intraoral application of strong acidic or salt stimuli induces irritation that progressively increases across trials (sensitization), whereas irritation elicited by nicotine progressively decreases (desensitization). We investigated whether nociceptive neurons in trigeminal subnucleus caudalis (Vc) exhibit increasing or decreasing patterns of firing to the intraoral application of these irritants. In rats anesthetized with halothane and thiopental, single-unit recordings were made from nociceptive neurons in superficial layers of dorsomedial Vc that responded to mechanical and noxious thermal and chemical stimulation of the tongue. NaCl (5M), citric acid (300 mM), pentanoic acid (300 mM) or nicotine (600 mM) were separately delivered to the tongue by constant flow (0.32 ml/min) for 15 or 25 min. NaCl, citric acid and pentanoic acid each elicited a progressive, significant increase in Vc neuronal firing over the initial 10 min to a plateau level that was maintained for the stimulus duration. Nicotine induced a significant increase in firing rate of Vc neurons within 6 min, followed by a decline back to the baseline level over the ensuing 10 min. Following a rest period, reapplication of nicotine no longer activated Vc neurons, indicative of self-desensitization. We additionally tested for nicotine cross-desensitization to acid. After recording the responses of Vc neurons to pentanoic acid and noxious heat, nicotine was then applied for 15 min. Post-nicotine responses to pentanoic acid were markedly reduced (to 13% of control), indicative of cross-desensitization; responses to noxious heat were also reduced to a lesser degree (to 71% of control). The progressive increase in Vc neuronal firing elicited by NaCl and acid, and the decline in firing after initial nicotinic excitation, resemble psychophysical patterns of sensitization and desensitization, respectively, and support the involvement of Vc neurons in the signaling of oral irritant sensations.

Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent structurally unrelated to any other intravenous anesthetics. We examined the effect of propofol on a rat vanilloid receptor that was expressed in the human embryonic kidney (HEK) 293 cells by using calcium imaging method. Propofol caused a concentration-dependent increase in [Ca 2+ ] i in the HEK293 cells with the receptor. These responses were inhibited by removing extracellular calcium ions. The propofol-evoked increase in [Ca 2+ ] i in the HEK293 cells with the receptor was partially inhibited by capsazepine, a competitive antagonist of capsaicin. We conclude that propofol acts as an agonist for the receptor.

Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann glial cells in the cerebellum have Ca 2+ -permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–type glutamate receptors (AMPARs) assembled without the GluR2 subunit. To elucidate the role of these Ca 2+ -permeable AMPARs, we converted them into Ca 2+ -impermeable receptors by adenoviral-mediated delivery of the GluR2 gene. This conversion retracted the glial processes ensheathing synapses on Purkinje cell dendritic spines and retarded the removal of synaptically released glutamate. Furthermore, it caused multiple innervation of Purkinje cells by the climbing fibers. Thus, the glial Ca 2+ -permeable AMPARs are indispensable for proper structural and functional relations between Bergmann glia and glutamatergic synapses.

A one-year-and-ten-months-old male infant with Arima syndrome, a very rare genetic disorder, underwent urgent insertion of a catheter for continuous ambulatory peritoneal dialysis (CAPD) under general anaesthesia. During the procedure he showed QRS-interval changes caused by hyperkalaemia which was successfully treated with calcium gluconate. The management and intraoperative complications of this syndrome are reported and available literature reviewed.

A 67-year-old male complaining of general fatigue was diagnosed as liver cirrhosis (anti HCV-Ab positive) with a hepatocellular carcinoma in the anterior segment of the liver with remarkable portal tumor thrombus attained to the extrahepatic portal vein. Right lobectomy of the liver and evacuation of the portal tumor thrombus were performed. The histopathological findings revealed moderately-poorly differentiated hepatocellular carcinoma. In the resected specimen, multiple, small and white nodules were scattered which were all diagnosed as distal portal tumor thrombi, but no lesion suspecting of the primary lesion was found. It is thought that the tumor in this case invaded the portal vein in an extremely early phase and expressed widely through the portal vein both distal and peripheral sides.

Tyrosine kinase inhibitors (TKIs) have provided promising anti-cancer activities, but intrinsic or acquired resistance to these drugs is a major problem. To overcome this resistance, we have used microarray analysis to identify a signature of intrinsic drug resistance in human pancreatic cancer cells, and applied this gene expression profile to silico drug screening for potential drugs for pancreatic cancer therapy. The potency of dasatinib (a multiple family TKI) was assessed against a panel of 14 human pancreatic cancer cell lines. This drug is undergoing clinical trials for pancreatic cancers. Nine of fourteen pancreatic cell lines were growth inhibited by dasatinib. Three dasatinib-resistant (MiaPaCa2, Panc1, SU8686) and three -sensitive (Panc0504, Panc1005, Panc0403) pancreatic cancer cell lines were used in microarray analysis to compare the gene expression profiles. A total of 598 genes were differentially expressed in dasatinib-resistant cell lines compared to the sensitive cell lines. To discover therapeutic drugs that sensitize pancreatic cancer cells to dasatinib, we performed in silico drug screening using the Connectivity Map database (CMAP). The gene signature induced by thioridazine in CMAP showed a “glove in hand” pattern to that found in dasatinib-resistant versus -sensitive pancreatic cancer cell lines. Thioridazine belongs to the phenothiazine family including chlorpromazine, perphenazine, penfluridol, and pimethixene. Each was examined. Assays of cell proliferaton, cell cycle, and Annexin V showed that each was effective at inhibiting the cell cycle and inducing apoptosis. Penfluridol (a calcium channel inhibitor) was the most potent against both the dasatinib-resistant and -sensitive pancreatic cancer cell lines. Drug combination studies of penfluridol and either dasatinib or gemcitabine (FDA-approved for pancreatic cancer) showed synergistic enhancement of cytotoxicity. Mechanistic investigations suggested that multiple signaling pathways were suppressed by penfluridol. These studies suggest a potential novel class of drugs for treatment of pancreatic cancers. Citation Format: Wenwen Chien, Kian Leong Lee, Qiaoyang Sun, Peer Wuensche, Makoto Sudo, Lorenz Poellinger, Jeffrey W. Tyner, Henry Yang, H. Phillip Koeffler. Identification of penfluridol as potential treatment for pancreatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1291. doi:10.1158/1538-7445.AM2013-1291

To clarify the role of the ventromedial hypothalamus (VMH)-sympathetic nervous system in insulin-independent glucose uptake in peripheral tissues, tissue glucose uptake was assessed in vivo by the 2-[3H]deoxyglucose method during electrical stimulation of the VMH in anesthetized rats. VMH stimulation significantly increased the rate constant of glucose uptake in brown adipose tissue (BAT), heart and skeletal muscles, but not in white adipose tissue and brain. The effect of VMH stimulation on glucose uptake in BAT was abolished by local sympathetic denervation, indicating that the increase in glucose uptake is mediated by the sympathetic nerves. Electrical stimulation of the lateral hypothalamus, on the other hand, had no appreciable effects on 2-[3H]deoxyglucose uptake in any tissues. Changes in glucose transporters after VMH stimulation were also examined by the [3H]cytochalasin B binding method using sarcolemmal membranes isolated from heart muscle. Scatchard analysis of cytochalasin B binding indicated that VMH stimulation did not alter both the number and affinity (dissociation constant) of glucose transporters in the heart sarcolemmal membranes, whereas insulin administration increased the number of transporters in the membranes. These results suggest that the mechanism by which VMH stimulation increases glucose uptake in muscle is different from that of insulin.

Effects of electrical and chemical stimulation of the ventromedial (VMH) and lateral hypothalamic (LH) nuclei on glucose uptake in peripheral tissues were studied by the 2-deoxy-D-[3H]glucose (2-[3H]DG) method in anesthetized rats. Electrical stimulation of the VMH increased the rate constant of glucose uptake in brown adipose tissue (BAT; 8 times), heart (3 times), and skeletal muscles (1.5 times) but not in white adipose tissue, diaphragm, and brain, without detectable changes in plasma insulin levels. Chemical stimulation of the VMH by microinjection of L-glutamate also enhanced the rate constant of glucose uptake in BAT, heart, and skeletal muscles preferentially, which indicates that the enhancement of glucose uptake in these tissues is derived from activation of VMH neurons. The increased rate of glucose uptake in BAT in response to VMH stimulation was effectively suppressed by surgical sympathetic denervation, suggesting a mediation of the sympathetic nerve in this effect. On the other hand, electrical stimulation of the LH had no appreciable effect on 2-[3H]DG uptake in any tissues. It is concluded that glucose uptake in certain peripheral tissues is accelerated selectively by activation of VMH neurons, the action of which is independent of plasma insulin but which is probably via the sympathetic nervous system.