Thermus thermophilus polyploid cells directly imaged by X-ray laser diffraction.

Thermus thermophilus is reportedly polyploid and carries four to five identical genome copies per cell, based on molecular biological experiments. To directly detect polyploidy in this bacterium, we performed live cell imaging by X-ray free-electron laser (XFEL) diffraction and observed its internal structures. The use of femtosecond XFEL pulses enables snapshots of live, undamaged cells. For successful XFEL imaging, we developed a bacterial culture method using a starch- and casein-rich medium that produces a predominance of rod-shaped cells shorter than the focused XFEL beam size, which is slightly smaller than 2 µm. When cultured in the developed medium, the length of T. thermophilus cells, which is typically ~4 µm, was less than half its usual length. We placed living cells in a micro-liquid enclosure array and successively exposed each enclosure to a single XFEL pulse. A cell image was successfully obtained by the coherent diffractive imaging technique with iterative phase retrieval calculations. The reconstructed cell image revealed five peaks, which are most likely to be nucleoids, arranged in a row in the polyploid cell without gaps. This study demonstrates that XFELs offer a novel approach for visualizing the internal nanostructures of living, micrometer-sized, polyploid bacterial cells.

Tumor DNA in Peritoneal Lavage as a Novel Biomarker for Predicting Peritoneal Recurrence in Patients With Gastric Cancer.

BACKGROUND: Peritoneal lavage cytology positivity (CY1) has been identified as a prognostic factor for distant metastases that is equivalent to peritoneal dissemination in Japan. Peritoneal lavage cytology is usually diagnosed by microscopic findings; a diagnostic procedure using a liquid biopsy (LB) technique has not yet been established. PATIENTS AND METHODS: We evaluated the feasibility of a LB approach using peritoneal lavage samples from 15 patients with gastric cancer. Samples were collected from both the Douglas pouch and the left subdiaphragmatic area, and cell-free DNA was extracted for analysis of TP53 mutations using droplet digital polymerase chain reaction. RESULTS: All 10 patients with CY1 had positive cytology for the left subdiaphragmatic specimen. However, only six out of the 10 patients had positive cytology for their Douglas pouch specimens, and these six patients had peritoneal tumor DNA (ptDNA) in these specimens. In all five patients with CY0, ptDNA was not detected. The overall survival was significantly shorter in the ptDNA-positive group than in the ptDNA-negative group. The survival of the group with a high amount of DNA from free intraperitoneal cells (ficDNA) was significantly worse than that of those with a low amount. In contrast, the group with a high amount of DNA from peritoneal cell-free DNA (pcfDNA) had significantly better survival than the group with a low amount. CONCLUSION: LB cytology showed equivalent utility to that of conventional microscopic examinations regarding its diagnostic ability. Therefore ptDNA, pcfDNA and ifcDNA are expected to be useful as prognostic factors.

Multiancestry genomic and transcriptomic analysis of gastric cancer.

Gastric cancer is among the most common malignancies worldwide, characterized by geographical, epidemiological and histological heterogeneity. Here, we report an extensive, multiancestral landscape of driver events in gastric cancer, involving 1,335 cases. Seventy-seven significantly mutated genes (SMGs) were identified, including ARHGAP5 and TRIM49C. We also identified subtype-specific drivers, including PIGR and SOX9, which were enriched in the diffuse subtype of the disease. SMGs also varied according to Epstein-Barr virus infection status and ancestry. Non-protein-truncating CDH1 mutations, which are characterized by in-frame splicing alterations, targeted localized extracellular domains and uniquely occurred in sporadic diffuse-type cases. In patients with gastric cancer with East Asian ancestry, our data suggested a link between alcohol consumption or metabolism and the development of RHOA mutations. Moreover, mutations with potential roles in immune evasion were identified. Overall, these data provide comprehensive insights into the molecular landscape of gastric cancer across various subtypes and ancestries.

The first case of robotic-assisted transabdominal retrorectus repair for incisional hernia in Japan.

Extraperitoneal mesh repair for ventral hernia has garnered attention and its rate has been increasing due to concerns for the potential complications of intraperitoneal mesh repair. Recently, robotic-assisted ventral hernia repair is highlighted as a solution to the technically demanding nature of laparoscopic transabdominal or enhanced-view totally extraperitoneal retrorectus ventral hernia repair. A 78-year-old man, who had undergone robot-assisted radical prostatectomy 10 months earlier, presented with an incisional hernia of European Hernia Society Classification M3W2, length 4 cm, width 5 cm with rectus diastasis. A right single-docking robotic-assisted transabdominal retrorectus repair was performed using a 21 by 14 cm self-gripping mesh and anterior wall reconstruction was done by 0 barbed nonabsorbable running suture. There were no complications and recurrence observed during a 7 months postoperative period. Single-docking robotic-assisted transabdominal retrorectus repair was considered a good option for midline moderate-size incisional hernias from the point of view of the ease of suturing, adequateness of dissection and prevention of bowel injury.

Factors Contributing to Tumor Shrinkage after Peptide Receptor Radionuclide Therapy in Patients with Unresectable Neuroendocrine Tumors.

Peptide receptor activation therapy (PRRT) is a promising treatment option for metastatic neuroendocrine tumors (NETs). However, predicting tumor shrinkage before treatment is challenging. We analyzed the shrinkage rate of each metastatic tumor lesion to identify predictive factors related to shrinkage. Patients with metastatic NET who underwent PRRT were included in this retrospective study. For each patient, between one to five metastatic lesions were selected in descending order of size, and the change in the maximum tumor diameter after treatment was defined as the shrinkage rate per lesion (L-SR). We analyzed the relationship between pretreatment clinicopathological factors and L-SR. The median L-SR of all 75 lesions in 20 patients was 20% (95% CI: 4.8−26.1%). While previous treatment with cytotoxic agents (34.4%, p < 0.05) and primary tumor of the pancreas (27.8%, p < 0.05) were significantly favorable factors, a primary tumor of the rectum was significantly more resistant to shrinkage (−20.5%, p < 0.001). Therefore, lesion-based analysis of PRRT for NETs showed that pancreatic NET and previous treatment with cytotoxic agents were favorable factors for tumor shrinkage; however, rectal NET was a factor associated with resistance to shrinkage.

Case reports: chemoradiotherapy for locally advanced neuroendocrine carcinoma of the gallbladder.

Neuroendocrine carcinoma (NEC) is a rare subtype of malignant gallbladder tumor. Although surgical resection is the only potentially curative therapy for gallbladder NEC, most cases are surgically unresectable because of advanced stage disease and/or biologically aggressive behavior. The standard palliative treatment for malignant gallbladder tumors is chemotherapy; however, the efficacy of chemoradiotherapy in the treatment of gallbladder tumors is controversial. Here, we report a case of gallbladder NEC that showed a durable response to chemoradiotherapy. A 68-year-old Japanese man presented with a huge gallbladder tumor with liver and duodenal invasion. Pathological findings revealed poorly differentiated NEC of the gallbladder. After seven cycles of chemotherapy comprising cisplatin and irinotecan, computed tomography (CT) revealed remarkable tumor shrinkage, but an enlarged portal lymph node. The patient was treated with 50.4 Gy in 28 fractions with two cycles of cisplatin and etoposide. After chemoradiotherapy, the enlarged lymph node also decreased in size. Maximum standardized uptake value of fluorodeoxyglucose-positron emission tomography/CT(FDG-PET/CT) changed from 8.2 to physiological accumulation. We defined this condition as a complete response on both enhanced CT and FDG-PET/CT; therefore, we did not perform systemic treatment and only observed his condition. This patient remained healthy with no recurrence at 3 years after chemoradiotherapy.

Evaluation of postgastrectomy symptoms and daily lives of small remnant distal gastrectomy for upper-third gastric cancer using a large-scale questionnaire survey.

Aim: Total gastrectomy (TG) is often performed for proximal gastric cancer. Small remnant distal gastrectomy (SRDG) can also be used in cases where surgical margins can be secured. The impact of preserving proximal small remnant stomach on postoperative quality of life (QOL) has not been fully elucidated. In the present study, we compared postgastrectomy symptoms and daily lives between patients undergoing SRDG and those undergoing TG for proximal gastric cancer using the developed Postgastrectomy Syndrome Assessment Scale (PGSAS)-45. Methods: Of the 1909 patients enrolled in the PGSAS NEXT study, univariate analysis of 19 main outcomes measures (MOMs) of PGSAS-45 was performed in patients undergoing TG (n = 1020) or SRDG (n = 54). Multiple regression analysis was performed with several clinical factors as explanatory variables. Results: There was no difference in age and sex between TG and SRDG groups. In SRDG group, postoperative period was shorter, the rates of laparoscopic approach and preservation of the celiac branch of the vagus nerve were higher, and the rates of clinical stage III/IV disease, ≥D2 dissection, and combined resection with other organs were lower than in the TG group significantly (P < .05). SRDG was associated with significantly lower symptoms and better daily lives than TG in 12 and 13 of 19 MOMs in PGSAS-45 by univariate and multiple regression analyses, respectively (P < .05). Several other clinical factors were also associated with certain MOMs. Conclusion: The PGSAS-45 revealed that SRDG was associated with better postgastrectomy symptoms and daily lives than TG.

Effectiveness of Naldemedine Compared with Magnesium Oxide in Preventing Opioid-Induced Constipation: A Randomized Controlled Trial.

Opioid-induced constipation (OIC) may occur in patients receiving opioid treatment, decreasing their quality of life (QOL). We compared the effectiveness of magnesium oxide (MgO) with that of naldemedine (NAL) in preventing OIC. This proof-of-concept, randomized controlled trial (registration number UMIN000031891) involved 120 patients with cancer scheduled to receive opioid therapy. The patients were randomly assigned and stratified by age and sex to receive MgO (500 mg, thrice daily) or NAL (0.2 mg, once daily) for 12 weeks. The change in the average Japanese version of Patient Assessment of Constipation QOL (JPAC-QOL) from baseline to 2 weeks was assessed as the primary endpoint. The other endpoints were spontaneous bowel movements (SBMs) and complete SBMs (CSBMs). Deterioration in the mean JPAC-QOL was significantly lower in the NAL group than in the MgO group after 2 weeks. There were fewer adverse events in the NAL group than in the MgO group. Neither significant differences in the change in SBMs between the groups nor serious adverse events/deaths were observed. The CSBM rate was higher in the NAL group than in the MgO group at 2 and 12 weeks. In conclusion, NAL significantly prevented deterioration in constipation-specific QOL and CSBM rate compared with MgO.

Assessment of Ultra-Early-Stage Liver Fibrosis in Human Non-Alcoholic Fatty Liver Disease by Second-Harmonic Generation Microscopy.

Non-alcoholic fatty liver disease (NAFLD) is associated with the chronic progression of fibrosis. In general, the progression of liver fibrosis is determined by a histopathological assessment with a collagen-stained section; however, the ultra-early stage of liver fibrosis is challenging to identify because of the low sensitivity in the collagen-selective staining method. In the present study, we demonstrate the feasibility of second-harmonic generation (SHG) microscopy in the histopathological diagnosis of the liver of NAFLD patients for the quantitative assessment of the ultra-early stage of fibrosis. We investigated four representative NAFLD patients with early stages of fibrosis. SHG microscopy visualised well-matured fibrotic structures and early fibrosis diffusely involving liver tissues, whereas early fibrosis is challenging to be identified by conventional histopathological methods. Furthermore, the SHG emission directionality analysis revealed the maturation of each collagen fibre of each patient. As a result, SHG microscopy is feasible for assessing liver fibrosis on NAFLD patients, including the ultra-early stage of liver fibrosis that is difficult to diagnose by the conventional histopathological method. The assessment method of the ultra-early fibrosis by using SHG microscopy may serve as a crucial means for pathological, clinical, and prognostic diagnosis of NAFLD patients.

Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA0-Tyr3-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. METHODS: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. RESULTS: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. CONCLUSION: PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

Retrospective study of peptide receptor radionuclide therapy for Japanese patients with advanced neuroendocrine tumors.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is an innovative treatment for advanced somatostatin-positive neuroendocrine tumors (NETs). PRRT cannot be performed in Japan because there is no approval or insurance cover so far. METHODS: We relied on foreign institutions to perform PRRT for Japanese patients with NETs. We retrospectively evaluated the safety and efficacy of PRRT. The inclusion criteria were pathologically confirmed well-differentiated NET and visible tumor uptake on pre-therapeutic somatostatin receptor scintigraphy. 177 Lu-DOTA-TOC was used as the standard treatment, and patients received three infusions every 8 weeks. Until the end of 2017, combination treatment with 90 Y and 177 Lu-DOTA-TOC was performed using the same protocol. RESULTS: Thirty-five patients were evaluated, and the primary lesions were pancreas, rectum, small intestine, stomach, and other locations. The partial response rate was 42.9%. Progression-free survival (PFS) was 12.8 months and overall survival was 42.8 months. There was no significant difference in PFS between front-line and late-line PRRT (11.0 months vs 28.0 months; P = .383). Severe adverse events included lymphocytopenia (20.0%) and thrombocytopenia (5.7%). Myelodysplastic syndrome occurred in one case. CONCLUSION: PRRT was effective and safe for Japanese patients with advanced NETs. PRRT was equally effective as front-line and late-line treatment.

Precision modeling of gall bladder cancer patients in mice based on orthotopic implantation of organoid-derived tumor buds.

Genetically engineered mice (GEM) are the gold standard for cancer modeling. However, strict recapitulation of stepwise carcinogenesis from a single tumor-initiating epithelial cell among genetically intact cells in adults is not feasible with the currently available techniques using GEM. In previous studies, we partially overcame this challenge by physically isolating organs from adult animals, followed by genetic engineering in organoids and subcutaneous inoculation in nude mice. Despite the establishment of suitable ex vivo carcinogenesis models for diverse tissues, tumor development remained ectopic and occurred under immunodeficient conditions. Further refinement was, therefore, necessary to establish ideal models. Given the poor prognosis and few models owing to the lack of gall bladder (GB)-specific Cre strain, we assumed that the development of authentic models would considerably benefit GB cancer research. Here, we established a novel model using GB organoids with mutant Kras and Trp53 loss generated in vitro by lentiviral Cre transduction and CRISPR/Cas9 gene editing, respectively. Organoid-derived subcutaneous tumor fragments were sutured to the outer surface of the GB in syngeneic mice, which developed orthotopic tumors that resembled human GB cancer in histological and transcriptional features. This model revealed the infiltration of similar subsets of immune cells in both subcutaneous and orthotopic tumors, confirming the appropriate immune environment during carcinogenesis. In addition, we accurately validated the in vivo efficacy of gemcitabine, a common therapeutic agent for GB cancer, in large cohorts. Taken together, this model may serve as a promising avatar of patients with GB cancer in drug discovery and precision medicine.

Quantitative evaluation of SARS-CoV-2 inactivation using a deep ultraviolet light-emitting diode.

Inactivation technology for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is certainly a critical measure to mitigate the spread of coronavirus disease 2019 (COVID-19). A deep ultraviolet light-emitting diode (DUV-LED) would be a promising candidate to inactivate SARS-CoV-2, based on the well-known antiviral effects of DUV on microorganisms and viruses. However, due to variations in the inactivation effects across different viruses, quantitative evaluations of the inactivation profile of SARS-CoV-2 by DUV-LED irradiation need to be performed. In the present study, we quantify the irradiation dose of DUV-LED necessary to inactivate SARS-CoV-2. For this purpose, we determined the culture media suitable for the irradiation of SARS-CoV-2 and optimized the irradiation apparatus using commercially available DUV-LEDs that operate at a center wavelength of 265, 280, or 300 nm. Under these conditions, we successfully analyzed the relationship between SARS-CoV-2 infectivity and the irradiation dose of the DUV-LEDs at each wavelength without irrelevant biological effects. In conclusion, total doses of 1.8 mJ/cm2 for 265 nm, 3.0 mJ/cm2 for 280 nm, and 23 mJ/cm2 for 300 nm are required to inactivate 99.9% of SARS-CoV-2. Our results provide quantitative antiviral effects of DUV irradiation on SARS-CoV-2, serving as basic knowledge of inactivation technologies against SARS-CoV-2.

Phase II study of temozolomide monotherapy in patients with extrapulmonary neuroendocrine carcinoma.

Extrapulmonary neuroendocrine carcinoma (EPNEC) is a lethal disease with a poor prognosis. Platinum-based chemotherapy is used as the standard first-line treatment for unresectable EPNEC. Several retrospective studies have reported the results of the utilization of temozolomide (TMZ) as a drug for the second-line treatment for EPNEC. Patients with unresectable EPNEC that were resistant to platinum-based combination chemotherapy were recruited for a prospective phase II study of TMZ monotherapy. A 200 mg/m2 dose of TMZ was given from day 1 to day 5, every 4 weeks. Response rate (RR) was evaluated as the primary end-point. The presence of O6 -methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research. Thirteen patients were enrolled in this study. Primary lesions were pancreas (n = 3), stomach (n = 3), duodenum (n = 1), colon (n = 1), gallbladder (n = 1), liver (n = 1), uterus (n = 1), bladder (n = 1), and primary unknown (n = 1). Each case was defined as pathological poorly differentiated neuroendocrine carcinoma from surgically resected and/or biopsied specimens. The median Ki-67 labeling index was 60% (range, 22%-90%). The RR was 15.4%, progression-free survival was 1.8 months (95% confidence interval [CI], 1.0-2.7), overall survival (OS) was 7.8 months (95% CI, 6.0-9.5), and OS from first-line treatment was 19.2 months (95% CI, 15.1-23.3). No grade 3 or 4 hematological toxicity had occurred and there was one case of grade 3 nausea. One case presented MGMT deficiency and this case showed partial response. Temozolomide monotherapy is a feasible, modestly effective, and safe treatment for patients with unresectable EPNEC following platinum-based chemotherapy, especially those with MGMT deficiency.

Defined lifestyle and germline factors predispose Asian populations to gastric cancer.

Germline and environmental effects on the development of gastric cancers (GC) and their ethnic differences have been poorly understood. Here, we performed genomic-scale trans-ethnic analysis of 531 GCs (319 Asian and 212 non-Asians). There was one distinct GC subclass with clear alcohol-associated mutation signature and strong Asian specificity, almost all of which were attributable to alcohol intake behavior, smoking habit, and Asian-specific defective ALDH2 allele. Alcohol-related GCs have low mutation burden and characteristic immunological profiles. In addition, we found frequent (7.4%) germline CDH1 variants among Japanese GCs, most of which were attributed to a few recurrent single-nucleotide variants shared by Japanese and Koreans, suggesting the existence of common ancestral events among East Asians. Specifically, approximately one-fifth of diffuse-type GCs were attributable to the combination of alcohol intake and defective ALDH2 allele or to CDH1 variants. These results revealed uncharacterized impacts of germline variants and lifestyles in the high incidence areas.

Development of a Simple and Practical Delirium Screening Tool for Use in Surgical Wards.

BACKGROUND: Delirium is an important and common medical condition, particularly in hospitalized patients, that is associated with adverse outcomes. The identification, prevention, and treatment of delirium are increasingly regarded as major public health priorities. PURPOSE: The aim of this study was to create a simple-to-use screening tool for delirium in hospitalized patients using clinical manifestations of delirium regularly observed by nurses. METHODS: This study was conducted using data on 2,168 patients who had been admitted to the surgical ward between January 2011 and December 2014. Data were collected retrospectively from medical records. Univariate and multivariate analyses were performed, and a logistic regression model was constructed for the development of a predictive screening tool. After constructing a new screening tool for delirium, a receiver operating characteristic curve was drawn, the most appropriate cutoff value was decided, and the area under the curve was obtained. Bootstrapping was used for the internal model validation. RESULTS: A screening tool for delirium (Subjective Delirium Screening Scale by Nurse) with a total score of 5 points was constructed as follows: 2 points for disorientation and 1 point each for restlessness, somnolence, and hallucination. The area under the curve for the Subjective Delirium Screening Scale by Nurse was 81.9% (95% CI [77.9%, 85.8%]), and the most appropriate cutoff value was determined to be 2 (sensitivity of 61.0% and specificity of 96.7%). Bootstrapped validation beta coefficients of the predictive factors were similar to the original cohort beta coefficients. CONCLUSIONS: We created a screening tool for delirium using factors that were regularly observed and recorded by nurses. This tool is simple and practical and has adequate diagnostic accuracy.

Epidemiological Features and Clinical Presentations of Acute Coronary Syndrome in Young Patients.

Objective Although acute coronary syndrome (ACS) is an uncommon entity in young patients, it constitutes an important problem due to the devastating effects of the disease on the more active lifestyle of young patients. At present, there are no guidelines regarding the prevention of ACS in young patients. Methods We performed a retrospective study of ACS patients between 2014 and 2017. Epidemiological data, clinical findings, and short-term outcomes were evaluated between young ACS patients (≤50 years old) and elderly ACS patients (>50 years old). Results Of a total of 361 consecutive ACS patients, 37 were young ACS patients (10.2%). Compared with elderly ACS patients, young ACS patients showed a higher prevalence of males (94.6% vs. 73.8%, p<0.001), current smoking (70.3% vs. 29.9%; p<0.001), and overweight persons (67.6% vs. 27.8%, p<0.001). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio was significantly lower in young ACS patients than in elderly ACS patients [0.17 (0.12-0.25) vs. 0.25 (0.18-0.37), p=0.002]. The prevalence of cardio-pulmonary arrest and percutaneous cardiopulmonary support use was higher in young ACS patients than in elderly ACS patients (24.3% vs. 8.6%, p=0.003, 16.2% vs. 3.1%, p<0.001). Conclusion The features were markedly different between young ACS patients and elderly ACS patients. In young ACS patients, smoking, being overweight, and a low EPA/AA ratio were distinctive risk factors, and more serious clinical presentations were observed at the onset of ACS than in older patients.

Lymphocyte-to-C-reactive protein ratio and score are clinically feasible nutrition-inflammation markers of outcome in patients with gastric cancer.

BACKGROUNDS: Systemic inflammation arising from complex host-tumour interactions is considered the seventh hallmark of cancer. The aim of this study was to assess the clinical feasibility of our newly developed 'lymphocyte-to-C-reactive protein (CRP) ratio' (LCR) and 'lymphocyte CRP score' (LCS) for predicting short- and long-term outcomes in patients with gastric cancer (GC). METHODS: In this observational study, we retrospectively analysed pre-operative LCRs and LCSs from 551 GC patients to elucidate these prognostic value for overall survival (OS) and disease free survival (DFS) and to clarify these predictive value for peri-operative risk of surgical site infection (SSI) in GC patients. RESULTS: Reduced pre-operative LCRs significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous and lymphatic vessel invasion, lymph node/hepatic/peritoneal metastasis, distant metastasis, and advanced tumour-node-metastasis stage. In the short-term outcome, low pre-operative LCR was an independent predictive factor for post-operative SSI. In the long-term outcome, low pre-operative LCR was an independent prognostic factor for OS and DFS, and prognostic impact of pre-operative LCR were verified in patients with metastatic and non-metastatic gastric cancer. Furthermore, our developed scoring system using lymphocyte and CRP (Lymphocyte-CRP Score; LCS) could also demonstrate all of clinical significance in GC patients, and both of LCR and LCS were significantly correlated with various representative nutrition markers, including BMI, PNI, and albumin, in GC patients. CONCLUSIONS: Pre-operative LCR and LCS are clinically feasible nutrition-inflammation markers in GC patients. Assessment of lymphocytes and CRP could aid physicians in determining surgical risk and oncological risk, thus facilitating appropriate peri-operative and post-operative management of patients with GC.

Identifying the needs for teaching fundamental knowledge of laparoscopic surgery: a cross-sectional study in Japan.

BACKGROUND: Recently, laparoscopic surgery (LS) has become a more common procedure than traditional open surgery. Although LS-related adverse events have been reported, there is no formal, standardized curriculum to teach the fundamentals of LS in Japan. Understanding surgeons' knowledge regarding LS is crucial for developing an educational curriculum. The purpose of this study was to determine the baseline knowledge on LS of surgeons and surgical trainees in Japan. METHODS: Participants completed 24 multiple-choice questions testing basic cognitive knowledge of LS and a questionnaire regarding the status of laparoscopic education. The examination was developed according to the 13 content domains of the Fundamentals of Laparoscopic Surgery (FLS) program. Scores were compared between post-graduate year (PGY) > 5 and PGY 1-5 participants. Data are expressed as median scores and interquartile ranges. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: A total of 195 surgeons and surgical trainees from 10 teaching hospitals (PGY1-5: 66, PGY > 5: 129) across Japan completed the examination. The median score in the entire cohort was 75 [67; 83] %, with significantly higher scores in the PGY > 5 group compared to the PGY1-5 group (79 [75; 83] % vs. 67 [58; 75] %, p < 0.001). The differences in performance were due to better scores for PGY > 5 group on the sections "equipment," "patient considerations," "abdominal access," "tissue handling," "hemorrhage and hemostasis," "tissue approximation," and "exiting the abdomen." Overall, the median scores in the "energy sources" and "establishment and physiology of the pneumoperitoneum" subsections were lower than in other domains. All participants agreed on the need for fundamental knowledge and a formal educational curriculum. CONCLUSIONS: Compared to experienced surgeons, surgical trainees had lesser knowledge about performing LS. Regardless of the years of experience, there are crucial knowledge gaps in specific areas regarding safe LS that should be addressed by implementing an educational curriculum.

Impact of vascular access site on procedural time of endomyocardial biopsy.

Endomyocardial biopsy (EMB) is widely used for the diagnosis of unexplained ventricular dysfunction and for assessment of cardiac allograft rejection. But, the impact of vascular access site on procedural time of EMB is not well-known. From February 2014 to May 2016, consecutive patients requiring EMB were prospectively enrolled in this study. Vascular access, by either the jugular or femoral vein, was randomly assigned. EMB was randomly performed by 3 pre-identified physicians based on practical experience in EMB. Each case was required to obtain at least 3 samples. The primary endpoint was to compare the total time spent in acquiring EMB from the right ventricular septum between the jugular and femoral vein access groups. The secondary endpoints were evaluation of each set (1st to 3rd attempt) of EMB times and safety. In addition, factors affecting the EMB procedural times were evaluated. A total of 49 consecutive patients requiring EMB (3.9 attempts/patient) were enrolled (the jugular group: 23, the femoral group: 26), and 156 myocardial samples (3.2 samples/patient) were obtained. There were no significant differences in total biopsy procedural time between the 2 groups (16.3 ± 7.4 vs. 20.8 ± 9.9 min, p = 0.075). Independent predictors for longer procedural time of the 1st attempt included femoral access, non-expert operators, and larger right atrium according to multiple linear regression analysis. The complication rates were not significantly different between the 2 groups, except for catheter kinking as a technical factor. Total biopsy time was not significantly different between the jugular and femoral venous access groups. However, the 1st attempt EMB procedural time by non-expert operators was longer when using the femoral approach, especially in cases involving a larger right atrium diameter.