Development of a performance rubric for transanal endoscopic rectal purse-string sutures.

BACKGROUND: Placing a transanal endoscopic rectal purse-string suture (taEPS) is the crucial first component of transanal total mesorectal excision (taTME). However, no structured training is available to improve the procedure-specific skills for taEPS. The aim of this study was to create a performance rubric to improve taEPS skills and provide preliminary evidence for its validity. METHODS: A performance rubric was created based on technical considerations for taEPS, identified by consulting with taTME surgical and performance assessment experts. Ten independent, blinded raters assessed 10 videotaped taEPS procedures of consecutive taTME cases, at National Cancer Center Hospital East (NCCHE), Chiba, Japan, in January 2018-March 2019 using the rubric and the Global Operative Assessment of Laparoscopic Skills (GOALS). Internal consistency and inter-rater reliabilities were calculated. Videotaped taEPS procedures were timed and assessed by the rubric. Correlation between rubric scores and suturing times were analyzed. RESULTS: The rubric consists of four items: loading the needle (LN), atraumatic needle passage (AP), planned suture path (PS), and overall performance (OA). Videotaped performances were graded on a 3-point Likert scale; scores were calculated as sums of the points. Cronbach's α for internal consistency was 0.713. Inter-rater reliabilities were LN: 0.73, AP: 0.76, PS: 0.71, and OA: 0.70. Rubric and GOALS scores were strongly correlated (r = 0.964, p < 0.001). In 112 consecutive taEPS performances, rubric scores were strongly correlated with suturing time (r = - 0.69, p < 0.001). Surgeons' experience with taTME was associated with rubric scores and suturing time. CONCLUSIONS: This study provides preliminary validation for the taEPS skill performance rubric. The rubric's structured training may facilitate skill acquisition by providing trainees with critical clinical considerations.

Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

BACKGROUND: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS: The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. RESULTS: The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. CONCLUSION: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.

ANTECEDENTES: La quimioterapia intraperitoneal con paclitaxel se considera una terapia experimental para el tratamiento de la carcinomatosis peritoneal. Este estudio tuvo como objetivo determinar la dosis recomendada y evaluar la eficacia clínica y la seguridad de la combinación de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal en pacientes con cáncer de páncreas y metástasis peritoneales. MÉTODOS: Se evaluaron las frecuencias de las toxicidades limitantes de la dosis, y la dosis recomendada se determinó en la fase I. El objetivo principal de la fase II fue la tasa de supervivencia global a 1 año. Los objetivos secundarios fueron los efectos antitumorales, los efectos de alivio de los síntomas, la seguridad y la supervivencia global. RESULTADOS: Las dosis recomendadas de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal fueron de 800, 75 y 20 mg/m2 , respectivamente. De los 46 pacientes incluidos en la fase II del estudio, la mediana de tiempo hasta el fracaso del tratamiento fue de 6,0 meses (rango, 0-22,6). Las tasas de respuesta y de control de la enfermedad fueron del 45% y 95%, respectivamente. La ascitis desapareció en el 40% de los pacientes, y la citología se negativizó en el 39% de los pacientes. La mediana del tiempo de supervivencia fue de 14,5 meses y la tasa de supervivencia global a 1 año del 60,9%. La cirugía de rescate se realizó en ocho (17%) pacientes, y los que se sometieron a cirugía sobrevivieron significativamente más tiempo que los que no fueron tratados quirúrgicamente (mediana de supervivencia no alcanzada versus 12,4 meses). Las toxicidades hematológicas de grado 3/4 ocurrieron en el 76% de los pacientes, mientras que los eventos adversos no hematológicos se presentaron en el 15% de los pacientes. CONCLUSIÓN: Agregar paclitaxel intraperitoneal tuvo eficacia clínica con una tolerabilidad aceptable. (UMIN000018878).

Delayed gastric emptying after pancreatoduodenectomy: comparison between invaginated pancreatogastrostomy and pancreatojejunostomy.

BACKGROUND: The association between delayed gastric emptying (DGE) after pancreatoduodenectomy (PD) and pancreatic reconstruction technique remain unclear. The aim of this study is to investigate whether the occurrence of DGE differs between pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). METHODS: A total of 83 patients who underwent subtotal stomach-preserving pancreatoduodenectomy was retrospectively analyzed, and the factors associated with clinically relevant DGE were explored. These patients were divided into a PG group and a PJ group according to the pancreatic reconstruction. DGE occurrence and its association with intra-abdominal complications was compared between the two types of pancreatic reconstruction. RESULTS: The overall incidence of DGE was 27.7%. Intra-abdominal complications including pancreatic fistula were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. In addition, DGE with intra-abdominal complications tended to be more frequent in PG, despite the fact that intra-abdominal complications occurred at a similar frequency in both groups. CONCLUSIONS: Intra-abdominal complications were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. We speculate that intra-abdominal complications affected patients with PG more and resulted in frequent occurrence of DGE.

Continuation of antithrombotic therapy increases minor bleeding but does not increase the risk other morbidities in open inguinal hernia repair: A propensity score-matched analysis.

PURPOSE: An aging population has led to an increased number of patients with cardiovascular comorbidities requiring antithrombotic therapy. Perioperatively, surgeons should consider the increased risk of bleeding and thrombotic events in patients continuing or discontinuing these medications. We aimed to analyze the safety of continued antithrombotic therapy during open inguinal hernia repair. METHODS: In this single-center, retrospective study, 4870 adult patients who underwent open inguinal hernia repair surgery by the same surgeon from 2008 January to 2019 March were included. Patients who underwent surgery while continuing antithrombotic therapy were included in the antithrombin group (n = 523) while those who were not under any antithrombotic therapy during the surgery were included in the control group (n = 4333). Using propensity score-matching, we then selected patients from each group with similar backgrounds. Surgery time, anesthesia time, postoperative bleeding, reoperation, and thrombotic event data were compared between the groups. Subgroup analysis based on the type of medications used was performed within the antithrombin group. RESULTS: Ten patients in the antithrombin group and seven patients in the control group experienced postoperative bleeding (p < 0.001). The rate of postoperative bleeding was the highest in patients taking multiple medications. However, most were managed conservatively. Three patients from the antithrombin group experienced thrombotic events postoperatively (p = 0.001). CONCLUSIONS: Patients receiving continued antithrombotic therapy had an increased risk of minor postoperative bleeding; however, they are a high-risk group for thrombotic events.

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies.

PURPOSE: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. METHODS: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. RESULTS: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. CONCLUSION: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.

BACKGROUND: Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. METHODS: This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m2 , administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. RESULTS: Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62·3 versus 63·8 months respectively; hazard ratio 1·01, 95 per cent c.i. 0·70 to 1·45; P = 0·964) and relapse-free survival (median 36·0 versus 39·9 months; hazard ratio 0·93, 0·66 to 1·32; P = 0·693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. CONCLUSION: The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).

Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study.

BACKGROUND: Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). METHODS: Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. RESULTS: From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. CONCLUSIONS: The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. TRIAL REGISTRATION: ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo.

Mucin core protein (MUC) 5AC is a gel-forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E-cadherin. However, it has not been elucidated whether COL4 and E-cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E-cadherin-expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E-cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E-cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells.

Laparoscopic reduction and repair for incarcerated obturator hernia: comparison with open surgery.

PURPOSE: Transabdominal preperitoneal (TAPP) repair for obturator hernia (OH) is not well established. Therefore, we evaluated the efficacy of TAPP for OH repair compared with open surgery. METHODS: We retrospectively analyzed patients who underwent surgery for OH at our hospital between 2006 and 2011. Since 2009, we have used TAPP repair for OH instead of open surgery. The clinical results of TAPP repair were compared with those of open surgery performed before 2008. RESULTS: Six patients with OH were treated by TAPP repair; occult contralateral OH was found by laparoscopic exploration in three (50 %) patients and was simultaneously repaired. Bowel incarceration was reduced by water pressure through Nelaton catheter in all but one patient. Bowel resection was performed in two patients after the laparoscopic assessment. For incarcerated OH, five of six cases were repaired using synthetic mesh, and the remaining case was addressed with simple peritoneal closure. Before 2008, six patients with OH underwent open surgery. The background of patients was comparable in the TAPP group and the open surgery group. There were no deaths in either group, but one metachronous contralateral OH occurred in the open surgery group within a short time frame, whereas none occurred in the TAPP group. CONCLUSIONS: TAPP repair, including the inspection of the viability of the incarcerated intestine and protective reduction and assessment of the entire groin area is an effective and minimally invasive strategy for OH patients.

Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial-mesenchymal transition is proposed to occur in various developmental processes and cancer progression. 'Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC). METHODS: We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n=117) using immunohistochemistry on tissue microarrays. RESULTS: Univariate and multivariate analyses revealed that, in addition to N classification (P=0.0420), the expression of E-cadherin (P=0.0208), N-cadherin (P=0.0038) and S100A4 (P=0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P=0.0143) in patients with EHCC. CONCLUSIONS: These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance.

Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas.

BACKGROUND: The International Union Against Cancer (UICC) staging system for perihilar cholangiocarcinoma changed in 2009. The aim of this study was to validate and optimize the UICC system for these tumours. METHODS: This retrospective study was conducted in eight Japanese hospitals between 2001 and 2010. Perihilar cholangiocarcinoma was defined as a cholangiocarcinoma that involves the hilar bile duct, independent of the presence or absence of a liver mass component. The stratification ability of the UICC tumour node metastasis (TNM) system was compared with that of a modified system. RESULTS: Of 1352 patients, 35.9, 44.8 and 12.6 per cent had Bismuth type IV tumours, nodal metastasis (N1) and distant metastasis (M1) respectively. T4 tumours (43.2 per cent) and stage IVA (T4 Nany M0; 36.3 per cent) disease were most common. Survival was not significantly different between patients with T3 versus T4 tumours (P = 0.284). Survival for patients with stage IVA disease was comparable to that for patients with stage IIIB tumours (T1-3 N1 M0) (P = 0.426). Vascular invasion, pancreatic invasion, positive margin, N1 and M1 status were identified as independent predictors of survival. When Bismuth type IV tumours were removed from the T4 determinants and N1 tumours grouped together, the modified grouping had a higher linear trend χ2 and likelihood ratio χ2 compared with the original system (245.6 versus 170.3 respectively and 255.8 versus 209.3 respectively). CONCLUSION: The present data suggest that minimal modification with removal of Bismuth type IV tumours from the T4 determinants and bundling of N1 disease may enhance the prognostic ability of the UICC system. However, this requires validation on an independent data set.

Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells.

BACKGROUND: We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs. METHODS: The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients. RESULTS: Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers. CONCLUSION: These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

Association of CD8+ T cell infiltration in oesophageal carcinoma lesions with human leucocyte antigen (HLA) class I antigen expression and survival.

Oesophageal cancer is one of the most aggressive tumours with a poor prognosis. However, little is known about the immune response in the tumour microenvironment. To investigate the role of immunosurveillance in the clinical course of oesophageal squamous cell carcinoma, 98 formalin-fixed, paraffin-embedded primary tumours were analysed using immunohistochemical methods for human leucocyte antigen (HLA) class I heavy chain and ß2-microglobulin expression and for CD4-, CD8- and CD57-positive cell infiltration. HLA class I expression of tumour cells was correlated positively with infiltration of CD8(+) T cells into the cancer nest, but not with the clinical course of disease. However, CD8(+) and CD4(+) T cell infiltration was correlated with prognosis. These results suggest that tumour antigen-specific cellular immune response plays a role in the clinical course of the disease and that HLA class I antigen expressed on tumour cells contribute to this association most probably by mediating the interactions between tumour cells and CD8(+) T cells.

Analysis of Chinese rabies virus isolates from 2003-2007 based on P and M protein genes.

UNLABELLED: Phylogenetic analysis of nucleotide sequences or deduced amino acid sequences of phosphoprotein (P protein), matrix (M) protein, and glycoprotein (G protein) genes of 18 Chinese isolates of Rabies virus (RABV) from 2003-2007 showed that these isolates formed a separate monophyletic lineage consisting of sub-lineages A and B. Compared with laboratory-fixed strains, recent Chinese isolates of sub-lineage B contained Val or Ala instead of Met69 in P protein, which is involved in generating truncated P proteins. In addition, one of these isolates CHpg3 had Pro instead of Ser63 and Leu instead of Ser64. Importantly, all functional domains of P and M proteins of all recent Chinese isolates were similar to those of laboratory-fixed strains. This study showed that although the recent Chinese RABV isolates belonged to a distinct lineage, their functional domains of P and M proteins were highly conserved. KEYWORDS: rabies virus; glycoprotein; phosphoprotein; matrix protein; China.

Endoscopic retrograde cholangiography versus peroral cholangioscopy to evaluate intraepithelial tumor spread in biliary cancer.

BACKGROUND AND STUDY AIMS: Localized-type bile duct carcinoma (LBDC) is often accompanied by extensive intraepithelial tumor spread (ITS) of 2 cm or more, which makes radical resection more difficult. This retrospective case review compares the diagnostic accuracy of endoscopic retrograde cholangiography (ERC) and peroral cholangioscopy (POCS) to detect ITS beyond the visible LBDC. PATIENTS AND METHODS: Forty-four consecutive patients with LBDC diagnosed between April 2004 and October 2008 who underwent radical resection with histopathological analysis were included in this study. Extensive ITS was found histopathologically in one-third of the cases (32 %). The outcome parameters were the presence or absence of extensive ITS and the extent of extensive ITS proximal and distal to the main tumor. RESULTS: In six cases it was not possible to pass the cholangioscope through the tumor sites. ERC correctly identified the presence of extensive ITS in 11/14 cases and did not yield any false-positive results. The three cases in which ERC was negative were all correctly identified by POCS plus biopsy since the cholangioscope could be passed in all three cases. The extent of extensive ITS was correctly diagnosed by ERC alone, ERC with POCS, and ERC with POCS plus mapping biopsy in 22 %, 77 %, and 100 % of cases, respectively. CONCLUSIONS: The presence of extensive ITS was correctly detected in 80 % of cases by ERC alone. POCS with mapping biopsy provided perfect diagnostic accuracy not only of the presence or absence but also of the extent of extensive ITS. However, POCS has the limitation that the cholangioscope cannot be passed through the tumor sites in approximately 15 % of cases.

Prognostic impact of para-aortic lymph node micrometastasis in patients with regional node-positive biliary cancer.

BACKGROUND: The presence of para-aortic lymph node metastasis in biliary cancer has a negative impact on prognosis. The relevance of para-aortic lymph node micrometastasis is unknown. METHODS: A total of 546 para-aortic lymph nodes from 49 patients with biliary cancer with positive regional nodes and negative para-aortic nodes were immunostained with epithelial marker CAM5.2 (specific for cytokeratins 7 and 8). Immunostained tumour foci were classified as micrometastases or isolated tumour cells (ITCs) according to their size (larger or smaller than 0.2 mm). RESULTS: CAM5.2-positive occult carcinoma cells in para-aortic lymph nodes were detected in nine (18 per cent) of 49 patients and in 18 (3.3 per cent) of 546 para-aortic nodes. There was no difference in postoperative survival between patients with and without CAM5.2-positive para-aortic nodes (P = 0.978), but survival for five patients with micrometastases was significantly worse than that for four patients with only ITCs (P = 0.047). CONCLUSION: In patients with regional node-positive and para-aortic node-negative biliary cancer, and occult cancer cells in para-aortic lymph nodes, prognosis was significantly worse in those with micrometastases than in patients with only ITCs. An efficient method of intraoperative detection of para-aortic lymph node micrometastases larger than 0.2 mm is needed.

A unique substitution at position 333 on the glycoprotein of rabies virus street strains isolated from non-hematophagous bats in Brazil.

The amino acid R or K at position 333 on the glycoprotein of the rabies virus is considered necessary for virulence in adult mice. Although some exceptions exist, substitution at this position causes expression of a phenotype that is either less pathogenic or non-virulent. To date, such substitutions have only been found in fixed strains of rabies virus. In this study, the authors found 333H, 333N, and 333Q substitutions at this position in rabies virus street strains isolated from non-hematophagous bats in Brazil. These strains showed pathogenicity and lethality on passage using adult mice with the intracerebral route and were confirmed rabies-positive by immunofluorescent assay. This suggests that these strains maintain virulence. Our findings indicate that rabies virus street strains with these substitutions exist in the field and may result in infection cycles.