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Aims Lymph node metastases (LNM) are associated with lethal prognosis in intrahepatic cholangiocarcinoma (ICC). Lymphadenectomy is crucial for accurate staging and hopes of possible oncological treatment. However, the therapeutic implications and optimal extent of lymphadenectomy remain contentious. Methods To clarify the prognostic value and optimal extent of lymphadenectomy, the therapeutic index (TI) for each lymph node was analyzed for 279 cases that had undergone lymphadenectomy in a multi-institutional database. Tumor localization was divided into hilar lesions (n = 130), right peripheral lesions (n = 60), and left peripheral lesions (n = 89). In addition, the lymph node station was classified as Level 1 (LV1: hepatoduodenal ligament node), Level 2 (LV2: postpancreatic or common hepatic artery nodes), or Level 3 (LV3: gastrocardiac, left gastric artery, or celiac artery nodes). Results Lymph node metastases were confirmed in 109 patients (39%). Five-y survival rates were 45.3% for N0 disease, 27.1% for LV1-LNM, 22.9% for LV2-LNM, and 7.3% for LV3-LNM (P < 0.001). LV3-LNM were the most frequent and earliest recurrence outcome, including multisite recurrence, followed by LV2, LV1, and N0 disease. The 5-year TI (5year-TI) for lymphadenectomy was 7.2 for LV1, 5.5 for LV2, and 1.9 for LV3. Regarding tumor location, hilar lesions showed 5-year TI > 5.0 in LV1 and LV2, whereas bilateral peripheral lesions showed 5-year TI > 5.0 in LV1. Conclusion The implications and extent of lymphadenectomy for ICC appear to rely on tumor location. In the peripheral type, the benefit of lymphadenectomy would be limited and dissection beyond LV1 should be avoided, while in the hilar type, lymphadenectomy up to LV2 could be recommended.

Supplementary Fig. S1 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer

Supplementary Figure 3 from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer

Supplementary Figure 4 from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer

Purpose: Long-term outcomes of patients with squamous cell carcinoma of the head and neck (SCCHN) remain unsatisfactory despite advances in combination of treatment modalities. SCCHN is characterized by locoregional spread and it is clinically accessible, making it an attractive target for intratumoral biological therapies.Experimental Design: OBP-301 is a type 5 adenovirus that contains the replication cassette in which the human telomerase reverse transcriptase promoter drives expression of the E1 genes. OBP-401 contained the replication cassette and the green fluorescent protein (GFP) gene. The antitumor effects of OBP-301 were evaluated in vitro by the sodium 30-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate assay and in vivo in an orthotopic xenograft model. Virus spread into the lymphatics was also orthotopically assessed by using OBP-401.Results: Intratumoral injection of OBP-301 resulted in the shrinkage of human SCCHN tumors orthotopically implanted into the tongues of BALB/c nu/nu mice and significantly recovered weight loss by enabling oral ingestion. The levels of GFP expression following ex vivo infection of OBP-401 may be of value as a positive predictive marker for the outcome of telomerase-specific virotherapy. Moreover, whole-body fluorescent imaging revealed that intratumorally injected OBP-401 could visualize the metastatic lymph nodes, indicating the ability of the virus to traffic to the regional lymphatic area and to selectively replicate in neoplastic lesions, resulting in GFP expression and cell death in metastatic lymph nodes.Conclusions: These results illustrate the potential of telomerase-specific oncolytic viruses for a novel therapeutic and diagnostic approach, termed theranostics, for human SCCHN.

A phase I dose-escalation study of telomerase-specific oncolytic adenovirus, OBP-301 (Telomelysin), is now under way in the United States to assess feasibility and to characterize its pharmacokinetics in patients with advanced solid tumors. The present preclinical study investigates whether OBP-301 and a chemotherapeutic agent that is commonly used for lung cancer treatment, gemcitabine, are able to enhance antitumor effects in vitro and in vivo. The antitumor effects of OBP-301 infection and gemcitabine were evaluated by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt assay. In vivo antitumor effects of intratumoral injection of OBP-301 in combination with systemic administration of gemcitabine were assessed on nu/nu mice s.c. xenografted with human lung tumors. OBP-301 infection combined with gemcitabine resulted in very potent synergistic cytotoxicity in human lung cancer cells. The three human lung cancer cell lines treated with OBP-301 for 24 hours tended to accumulate in S phase compared with controls. The proportion of cells in S phase increased from 43.85% to 56.41% in H460 cells, from 46.72% to 67.09% in H322 cells, and from 38.22% to 57.67% in H358 cells. Intratumoral injection of OBP-301 combined with systemic administration of gemcitabine showed therapeutic synergism in human lung tumor xenografts. Our data suggest that the combination of OBP-301 and gemcitabine enhances the antitumor effects against human lung cancer. We also found that the synergistic mechanism may be due to OBP-301–mediated cell cycle accumulation in S phase. These results have important implications for the treatment of human lung cancer.[Mol Cancer Ther 2009;8(4):980–7]

Supplementary Figure 1 from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer

Supplementary Figure Legends 1-4 from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer

Multimodal approaches combining drugs that differentially function is the most popular regimen for treating human cancer. Understanding the molecular mechanisms underlying the synergistic, potentiative, and antagonistic effects of drug combinations could facilitate the discovery of novel efficacious combinations. We previously showed that telomerase-specific replication-competent adenovirus (Telomelysin, OBP-301), in which the human telomerase reverse transcriptase promoter controls the adenoviral E1 gene expression, induces a selective antitumor effect in human cancer cells. Here, using E1-deleted replication-deficient adenovirus expressing the p53 tumor suppressor gene (Advexin, Ad-p53) and OBP-301, we investigate how these adenoviruses that kill tumor cells with different mechanisms could work in combination on human cancer. We found that E1-deficient Ad-p53 could kill cancer cells more efficiently in the presence of OBP-301 than Ad-p53 alone or OBP-301 alone, because Ad-p53 could become replication-competent by being supplied adenoviral E1 from coinfected OBP-301 in trans. Ad-p53 plus OBP-301 induced high levels of p53 protein expression without p21 induction, resulting in apoptotic cell death documented by active caspase-3 expression with a cytometric bead array and an increased subdiploid apoptotic fraction of the cell cycle. For in vivo evaluation, nude mice xenografted with human lung tumors received intratumoral injection of OBP-301 and/or Ad-p53. Analysis of the growth of implanted tumors showed an enhanced antitumor effect in combination therapy. Our data show that Ad-p53 in combination with OBP-301 induces not only oncolytic but also apoptotic cancer cell death and enhances antitumor activity in vitro and in vivo, providing potential merits as a multimodal treatment for human cancer. Mol Cancer Ther; 9(6); 1884–93. ©2010 AACR.

Supplementary Data from Telomerase-Specific Virotheranostics for Human Head and Neck Cancer

It has been postulated that the combination of intracavitary and interstitial brachytherapy (IC/IS) is effective and safe for large and irregularly shaped uterine cervical cancer patients. However, due to its invasiveness compared to conventional intracavitary brachytherapy (ICBT), it has to be said that the implementation speed of IC/IS is slow. Until now, there have been no guidelines for required equipment, human resources, and procedural guide focusing solely on IC/IS. The purpose of this guideline is to provide radiation oncologists and medical physicists who wish to start IC/IS with practical and comprehensive guidance for a safe IC/IS introduction and to help accelerate the spread of the utilization of IC/IS nationwide. This is the English translation of the Japanese IC/IS Guidelines, and it was created in an effort to share the Japanese approach to the management of locally advanced uterine cervical cancer worldwide.

Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI).This multicenter, open-label, single-arm study enrolled Japanese patients with non-small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI 20 kg/mOne hundred two patients were eligible and enrolled. The means and standard deviations for age and BMI were 71.0 ± 8.2 years and 17.47 ± 1.48 kg/mAnamorelin improved body weight and anorexia-related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability.Anamorelin is a drug that stimulates appetite and promotes weight gain. This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss. Anamorelin was found to improve body weight and anorexia-related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated. These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index.

To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world.The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed.Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning.The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Background: Lymph node metastasis (LNM) has been established as a critical risk factor for prognosis in intrahepatic cholangiocarcinoma (ICC). The clinical implications of lymph node dissection (LND) have been debated. This study aimed to clarify the prognostic impact of LND by multicenter retrospective analysis. Methods: A total of 310 ICC patients who had undergone curative resection between 2000 and 2016 were retrospectively analyzed. The prognostic impact of LND was estimated under an inverse probability of treatment weighting (IPTW) approach using propensity scores. Results: LND was performed for 224 patients (72%), with LNM pathologically confirmed in 90 patients (40%). Prognosis was poorer for patients with LNM (median survival, 16.9 months) than for those without (57.2 months; P < .0001). One-, 3-, and 5-year overall survival rates (OS) were comparable among LND+ (81.6%, 48.0%, and 37.5%, respectively) and LND- groups (81.6%, 55.4%, and 44.6%, respectively). However, advanced tumor, as characterized by larger tumor, multinodular lesions, and serosal invasion, was significantly more frequent in the LND+ group than in the LND- group. After IPTW adjusting for imbalances, 1-, 3-, and 5-year OS were better in the LND+ group (83.5%, 52.2%, and 42.8%, respectively) than in the LND- group (71.9%, 32.4%, and 23.4%, respectively; P = .046). LND thus showed significant prognostic impact (hazard ratio = 0.58, 95%CI = |0.39|-|0.84|, P = .005), especially in hilar ICC. However, peripheral ICC displayed no therapeutic benefit from LND. Conclusions: LND could have a significant role to play in improving oncologic outcomes. Therapeutic LND should be implemented on the basis of tumor location and tumor advancement.

A procedure-based laparoscopic liver resection (LLR) classification (IMM classification) stratified 11 different LLR procedures into 3 grades. IMM classification assessed the difficulty of LLR differently than an index-based LLR classification (IWATE criteria), which scored each procedure on an index scale of 12. We validated the difference of 3 IMM grades using an external cohort, evaluated the IMM classification using the scores of the IWATE criteria, and compared the performance of IMM classification with the IWATE criteria and the minor/major classification. Patients undergoing LLR without simultaneous procedures were selected from a prospectively maintained database at the Institut Mutualiste Montsouris (IMM cohort) and from the database of 43 Japanese institutions (JMI cohort). Surgical and postoperative outcomes were evaluated according to the 3 IMM grades using the JMI cohort. The 11 LLR procedures included in the IMM classification were scored according to the IWATE criteria. The area under the curves (AUCs) for surgical and postoperative outcomes were compared. In the JMI (n = 1867) cohort, operative time, blood loss, conversion rate, and major complication rate were significantly associated with a stepwise increase in grades from I to III (all, P

The original difficulty scoring system was revised after discussion at the 2nd International Consensus Conference on Laparoscopic Liver Resection held in Morioka (Iwate Prefecture) in Japan and renamed the IWATE criteria (a 4-level classification system involving 6 preoperative factors). We used Japanese and French cohorts to validate the IWATE criteria by evaluating their association with the procedure-based difficulty classification proposed by the Institut Mutualiste Montsouris.Patients who had undergone laparoscopic liver resection at multiple Japanese multi-institutions or the Institut Mutualiste Montsouris were assigned to the multiple Japanese multi-institution (n = 1,867) or Institut Mutualiste Montsouris cohort (n = 433). We analyzed clinical characteristics and outcomes according to the 4-level IWATE criteria difficulties (low, intermediate, advanced, and expert) and evaluated their association with 11 laparoscopic liver resection procedures in the Institut Mutualiste Montsouris classification (low, intermediate, and high levels).We found significant differences in age, surgical indications, and the 4-level IWATE criteria difficulties between the cohorts (all, P.001). Operation time and blood loss were significantly different among the 4-level difficulties in both cohorts (all, P.001). The rates of conversion, postoperative complications, liver failure, and in-hospital deaths also increased significantly with increasing difficulty (all, P.001). The IWATE criteria classified the three low-level Institut Mutualiste Montsouris procedures in the low-to-intermediate levels, the two intermediate-level procedures in the intermediate-to-advanced levels, and the six high-level procedures in the advanced-to-expert levels.We observed associations between the IWATE criteria and intraoperative and postoperative outcomes in the Japanese multi-institution and Institut Mutualiste Montsouris cohorts and thus validated the IWATE system.

This report covers the first multi-institutional study of independent monitor unit (MU)/dose calculation verification for the CyberKnife, Vero4DRT, and TomoTherapy radiotherapy delivery systems.A total of 973 clinical treatment plans were collected from 12 institutions. Commercial software employing the Clarkson algorithm was used for verification after a measurement validation study, and the doses from the treatment planning systems (TPSs) and verification programs were compared on the basis of the mean value ± two standard deviations. The impact of heterogeneous conditions was assessed in two types of sites: non-lung and lung.The dose difference for all locations was 0.5 ± 7.2%. There was a statistically significant difference (P 0.01) in dose difference between non-lung (-0.3 ± 4.4%) and lung sites (3.5 ± 6.7%). Inter-institutional comparisons showed that various systematic differences were associated with the proportion of different treatment sites and heterogeneity correction.This multi-institutional comparison should help to determine the departmental action levels for CyberKnife, Vero4DRT, and TomoTherapy, as patient populations and treatment sites may vary between the modalities. An action level of ±5% could be considered for intensity-modulated radiation therapy (IMRT), non-IMRT, and volumetric modulated arc radiotherapy using these modalities in homogenous and heterogeneous conditions with a large treatment field applied to a large region of homogeneous media. There were larger systematic differences in heterogeneous conditions with a small treatment field because of differences in heterogeneity correction with the different dose calculation algorithms of the primary TPS and verification program.

Background Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings.

Regio- and stereoselective hydrostannylation of alkyl ethynyl ethers generates alkenyl ethers, which are useful building blocks in organic synthesis. This efficient synthetic method, however, is limited. Here, we report not only an efficient method for a highly regio- and stereoselective Pd-catalyzed hydrostannylation of alkyl ethynyl ethers but also a scalable synthesis and construction of the core framework of luminamicin possessing all functional groups and stereocenters.

Marginal ulcer after pancreatoduodenectomy (PD) is a relatively common complication, but if massive bleeding or ulcer perforation occurs together with the marginal ulcer, this condition may be fatal.To identify the risk factors and management of marginal ulcer after PD.In all, 438 patients who underwent PD from 2003 to 2017 were retrospectively reviewed and analyzed. After surgery, all patients were administered a histamine H2 receptor antagonist (H2RA) or a proton pump inhibitor (PPI), which was continued after discharge. Marginal ulcer was diagnosed by endoscopy or surgery. The risk factors for marginal ulcer were then investigated using univariate and multivariate analyses.After a median follow-up time of 2.7 years, 29 patients (6.6%) developed marginal ulcer. Seventeen patients developed marginal ulcer within 1 year after PD, and 7 patients developed marginal ulcer more than 3 years after PD. All 8 patients who underwent surgery for the treatment of marginal ulcer developed acute peritonitis. Two patients with acute peritonitis died within 1 month after surgery. A multivariate analysis found that discontinuation of PPI treatment was the only independent risk factor for marginal ulcer development (P0.001). In contrast, sex, age, primary disease, procedure, operation time, volume of blood loss, pancreatic texture, development of postoperative pancreatic fistula, postoperative complications, poor glycemic control after PD, and discontinuation of H2RA therapy after PD were not significantly different between the patient group that developed marginal ulcer and the patient group that did not. Sixteen patients were not treated with antacids at the time of marginal ulcer development. The reason for discontinuation of antacids was the decision of the family physician in 8 cases and the decision of the patient in 3 cases.Marginal ulcer can still develop a long time after PD, and sometimes, it may be fatal. PPI administration should be continued even after a long time has passed, although this therapy is often discontinued for various reasons. It is therefore important for family physicians and patients to recognize the danger of marginal ulcer after PD.

BackgroundThe prognosis of intrahepatic cholangiocarcinoma (ICC) has been poor, because of the high recurrence rate even after curative surgery. This study aimed to evaluate the prognostic impact of surgical resection of recurrent ICC.Patients and methodsA total of 345 cases of ICC who underwent hepatectomy with curative intent in 17 institutions were retrospectively analyzed, focusing on recurrence patterns and treatment modalities for recurrent ICC.ResultsMedian survival time and overall 5-year recurrence-free survival rate were 17.8 months and 28.5%, respectively. Recurrences (n = 223) were classified as early (recurrence at ≤1 year, n = 131) or late (recurrence at >1 year, n = 92). Median survival time was poorer for early recurrence (16.3 months) than for late recurrence (47.7 months, pConclusionSurgical resection of recurrent ICC could improve survival after recurrence, especially for patients with intra- or extrahepatic recurrence as resectable oligo-metastases.

Postoperative pancreatic fistula (POPF) and its complications remain problems. This study evaluated combination treatment with modified Blumgart anastomosis and an original infection control method (complete packing method) following pancreatic head resection.This study included 374 consecutive patients who underwent pancreatic head resection: 103 patients underwent Cattell-Warren anastomosis (CWA); 170 patients underwent modified Kakita anastomosis (KA); and 101 patients underwent modified Blumgart anastomosis with the complete packing method (BAC). The outcomes of the KA and BAC groups were compared statistically.The POPF rate was significantly lower in the BAC group than in the KA group (28.8% vs 2.97%; p 0.01). The overall postoperative complication rate, including SSI and postoperative hemorrhage, was significantly lower in the BAC group.The combination of modified Blumgart anastomosis and the complete packing method is a simple and useful method for reducing the incidence of POPF and postoperative complications.

Background Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. Methods Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. Results Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. Conclusion LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.

To evaluate the usefulness of a novel contrast-injection protocol for high-resolution abdominal computed tomography angiography (CTA) using nitroglycerin (NTG). Abdominal CTA was performed in 80 patients using two 64-detector-row CT scanners. Forty patients were examined after administration of sublingual NTG (NTG group), while 40 were examined without NTG administration (non-NTG group). Arterial phase images were acquired with maximum intensity projection and volume rendering. Reduction rates: vessel cross-sectional areas ratio of 10 cm distal to origin at the superior mesenteric artery, contrast enhancements, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were assessed. Three reviewers evaluated degree of depiction of the peripancreatic vasculature using a four-point scale (1 = poor, 4 = excellent). Reduction rates were significantly lower in the NTG group (P

Highlights • 75% of pancreas transplantation is SPKT. • The optimal surgical management for graft perforation is still unknown. • Delayed graft duodenal perforation is very rare. • The omega loop may contribute to increased pressure by luminal congestion. • When delayed duodenal graft perforation occurs, graft excision may not be necessary., Introduction Pancreas transplantation is the best treatment option in selected patients with type 1 diabetes mellitus. Here we report a patient with a nonmarginal duodenal perforation five years after a simultaneous pancreas-living donor kidney transplantation (SPLKT). Presentation of case A 31-year old male who underwent SPLKT five years previously presented with severe abdominal pain. He had a marginal duodenal perforation four years later, treated by primary closure and drainage. Biopsy of the pancreas and duodenum graft at that time showed chronic rejection in the pancreas and acute inflammation with an ulcer in the duodenum. At presentation, computerized tomography scan showed mesenteric pneumatosis with enteric leak and ileal dilatation proximal to the anastomotic site. We performed emergent laparotomy and found a 1.0 cm perforation at the nonmarginal, posterior wall of the duodenum. Undigested fiber-rich food was extracted from the site and an omental patch placed over the perforation. An ileostomy was created proximal to the omega loop for decompression and a drain placed nearby. The postoperative course was unremarkable. Discussion There are only eight previous cases of graft duodenal perforation in the literature. Fiber-rich food residue passing through the anastomosis with impaction may have led to this perforation. Conclusion When a patient is stable, even in the presence of delayed duodenal graft perforation, graft excision may not be necessary. Intraoperative exploration should include Doppler ultrasound examination of the vasculature to rule out thrombosis as a contributor to ischemia. Tissue biopsy should be performed to diagnose rejection.

Background and objectives Peritoneal dissemination of gastric cancer is often associated with serosal infiltration. The aim of this study was to evaluate the clinical importance of peritoneal lavage cytology in patients with gastric carcinoma without serosal invasion. The incidence and impact on prognosis of positive cytology were analyzed. Methods Of 2768 patients with gastric cancer, outcomes and pathological characteristics of 973 patients were reviewed retrospectively. All patients underwent peritoneal lavage at laparotomy for curative or palliative resection of gastric cancer between 1999 and 2017. Among these, 479 who underwent surgery from January 1999 to March 2012 were also reviewed to analyze 5-year survival. Results Of 973 patients enrolled, 338 (35%) did not have serosal invasion, and peritoneal cytology was positive in 4/338 (1.2%). Of these four patients, one had submucosal invasion and three had muscularis propria invasion. Of 635 patients with serosal invasion, peritoneal cytology was positive in 74/635 (12%). Of 479 patients reviewed for survival, cytology was positive in 32/479, with 3/32 (9%) surviving for five years, and cytology was negative in 447 patients with 266/447 (60%) surviving for five years. Conclusions Cytologic evaluation should be routinely performed in patients with early-stage gastric cancer., Highlights • Patients with gastric carcinoma without serosal invasion can have positive cytology, although cytologic evaluation has a relatively low sensitivity. • Positive cytology is associated with a significantly worse prognosis. • Lymph node metastases and distant metastasis were significant risk factors for positive peritoneal cytology.

A graph G admits an H -covering if every edge in E ( G ) belongs to a subgraph of G isomorphic to H . Suppose G admits an H -covering. A bijection f from V ( G ) ∪ E ( G ) to { 1 , 2 , … , | V ( G ) | + | E ( G ) | } is called an H -magic labeling of G if ∑ v ∈ V ( H ′ ) f ( v ) + ∑ e ∈ E ( H ′ ) f ( e ) is constant for every subgraph H ′ of G isomorphic to H . An H -magic labeling f of G is called an H -supermagic labeling of G if f ( V ( G ) ) = { 1 , 2 , … , | V ( G ) | } . In this paper, we investigate C 4 -supermagic labelings of the Cartesian product of paths and graphs.

A woman in her 50s was found to have a pancreatic mass on abdominal ultrasound. The tumor measured 40 mm in diameter and included a cystic lesion and calcification. In this case, we suspected a diagnosis of solid pseudopapillary neoplasm (SPN) due to the findings observed on various images. However, we were unable to exclude the possibility that the lesion was a neuroendocrine tumor. Therefore, we performed endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA). In addition, in order to confirm the diagnosis of SPN, we performed minimized resection (segmental pancreatectomy). Obtaining a definitive preoperative diagnosis of SPN using EUS-FNA can guide the surgical approach.

ウイルスは本来,ヒトの細胞に感染し構造蛋白質を 産生することで複製・増殖し,その細胞を様々な機序 により破壊する.そのウイルス増殖機能に選択性を付 加することにより,ウイルスを癌細胞のみを標識し, 傷害する作用を発揮させることができる. ヒトのきわめて多くの癌細胞でテロメラーゼという 酵素活性が上昇していることが明らかになってい る.その詳細な生化学的作用についてはここでは割 愛するが,癌細胞の無制限増殖能に深く関わっている とされている.テロメラーゼは3つのサブユニットか ら構成されており,その中でも hTERTと呼ばれる部 分の発現レベルがテロメラーゼ活性に強く関わってい ることがわかっている.そこでわれわれはアデノウ イルス5型の増殖に必要なE1A遺伝子とE1B遺伝子 癌微小リンパ節転移を標的とするテロメラーゼ特異的制限増 殖型ウイルス製剤の開発 児 島 亨a*,渡 邉 雄 一b ,橋 本 悠 里a,c,黒 田 新 士a,山 崎 泰 源a,矢 野 修 也a, 田 澤 大a,c,宇 野 太a,c,香 川 俊 輔a,c,田 中 紀 章a,浦 田 泰 生b,藤 原 俊 義a,c

Oncolytic viruses engineered to replicate in tumour cells but not in normal cells could be used as tumour-specific vectors carrying the therapeutic genes. We previously developed a telomerase-specific oncolytic adenovirus, OBP-301, that causes cell death in human cancer cells with telomerase activities. Here, we further modified OBP-301 to express the wild-type p53 tumour suppressor gene (OBP-702), and investigated whether OBP-702 induces stronger antitumour activity than OBP-301. The antitumour effect of OBP-702 was compared to that of OBP-301 on OBP-301-sensitive (H358 and H460) and OBP-301-resistant (T.Tn and HSC4) human cancer cells. OBP-702 suppressed the viability of both OBP-301-sensitive and OBP-301-resistant cancer cells more efficiently than OBP-301. OBP-702 caused increased apoptosis compared to OBP-301 or a replication-deficient adenovirus expressing the p53 gene (Ad-p53) in H358 and T.Tn cells. Adenovirus E1A-mediated p21 and MDM2 downregulation was involved in the apoptosis caused by OBP-702. Moreover, OBP-702 significantly suppressed tumour growth in subcutaneous tumour xenograft models compared to monotherapy with OBP-301 or Ad-p53. Our data demonstrated that OBP-702 infection expressed adenovirus E1A and then inhibited p21 and MDM2 expression, which in turn efficiently induced apoptotic cell death. This novel apoptotic mechanism suggests that the p53-expressing OBP-702 is a promising antitumour reagent for human cancer and could improve the clinical outcome.