Spatial variability in the risk of death from COVID-19 in Italy.

OBJECTIVES: Italy has been badly affected by the COVID-19 pandemic and has one of the highest death tolls. We analyzed the severity of COVID-19 across all 20 Italian regions.METHOD: We manually retrieved the daily cumulative numbers of laboratory-confirmed cases and deaths attributed to COVID-19 in each region, and estimated the crude case fatality ratio and time delay-adjusted case fatality ratio (aCFR). We then assessed the association between aCFR and sociodemographic, health care and transmission factors using multivariate regression analysis.RESULTS: The overall aCFR in Italy was estimated at 17.4%. Lombardia exhibited the highest aCFR (24.7%), followed by Marche (19.3%), Emilia Romagna (17.7%) and Liguria (17.6%). Our aCFR estimate was greater than 10% for 12 regions. Our aCFR estimates were statistically associated with population density and cumulative morbidity rate in a multivariate analysis.CONCLUSION: Our aCFR estimates for Italy as a whole and for seven out of the 20 regions exceeded those reported for the most badly affected region in China. These findings highlight the importance of social distancing to suppress transmission to avoid overwhelming the health care system and reduce the risk of death.

Risk model for severe postoperative complications after total pancreatectomy based on a nationwide clinical database.

BACKGROUND: Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications. METHODS: Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato-Biliary-Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien-Dindo grade III needing reoperation, or grade IV-V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c-statistics and a calibration plot. RESULTS: A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30-day and in-hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c-statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81). CONCLUSION: The risk model may be used to predict severe complications after total pancreatectomy.

ANTECEDENTES: La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves. MÉTODOS: Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato-Bilio-Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien-Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración. RESULTADOS: Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59-0,81). CONCLUSIÓN: El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.

Assessing the potential impact of vector-borne disease transmission following heavy rainfall events: a mathematical framework.

Predicting the impact of natural disasters such as hurricanes on the transmission dynamics of infectious diseases poses significant challenges. In this paper, we put forward a simple modelling framework to investigate the impact of heavy rainfall events (HREs) on mosquito-borne disease transmission in temperate areas of the world such as the southern coastal areas of the USA. In particular, we explore the impact of the timing of HREs relative to the transmission season via analyses that test the sensitivity of HRE-induced epidemics to variation in the effects of rainfall on the dynamics of mosquito breeding capacity, and the intensity and temporal profile of human population displacement patterns. The recent Hurricane Harvey in Texas motivates the simulations reported. Overall, we find that the impact of vector-borne disease transmission is likely to be greater the earlier the HREs occur in the transmission season. Simulations based on data for Hurricane Harvey suggest that the limited impact it had on vector-borne disease transmission was in part because of when it occurred (late August) relative to the local transmission season, and in part because of the mitigating effect of the displacement of people. We also highlight key data gaps related to models of vector-borne disease transmission in the context of natural disasters. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.

Assessing reporting delays and the effective reproduction number: The Ebola epidemic in DRC, May 2018-January 2019.

On August 1, 2018, the Democratic Republic of Congo declared its 10th and largest outbreak of Ebola inflicting North Khivu and Ituri provinces. The spread of Ebola to Congolese urban centers along with deliberate attacks on the health care workers has hindered epidemiological surveillance activities, leading to substantial reporting delays. Reporting delays distort the epidemic incidence pattern misrepresenting estimates of epidemic potential and the outbreak trajectory. To assess the impact of reporting delays, we conducted a real-time analysis of the dynamics of the ongoing Ebola outbreak in the DRC using epidemiological data retrieved from the World Health Organization Situation Reports and Disease Outbreak News. We analyzed temporal trends in reporting delays, epidemic curves of crude and reporting-delay adjusted incidences and changes in the effective reproduction number, Rt. As of January 15, 2019, 663 Ebola cases have been reported in the Democratic Republic of Congo. The average reporting delay exhibited 81.1% decline from a mean of 17.4 weeks (95% CI 13-24.1) in May, 2018 to 3.3 weeks (95% CI 2.7-4.2) in September, 2018 (F-test statistic = 44.9, p = 0.0067). The Ebola epidemic has shown a two-wave pattern with the first surge in cases occurring between July 30 and August 13, 2018 and the second on September 24, 2018. During the last 4 generation intervals, the trend in the mean Rt has exhibited a slight decline (rho = -0.37, p < 0.001), fluctuating around 0.9 (range: 0-1.8). Our most recent estimate of R is at 0.9 (95% CI: 0.4, 1.1) during the last generation interval. Our most recent analysis of the Ebola outbreak in DRC indicates that the Ebola virus still active although transmission is characterized by a low fluctuating reproduction number. Yet, this pattern does not imply that the epidemic can be easily controlled particularly in the context of unstable epidemiological surveillance efforts hindered by unpredictable local violence.

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer.

PURPOSE: The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed. METHODS: The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011. RESULTS: The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS. CONCLUSION: Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00498225.

Incubation period as part of the case definition of severe respiratory illness caused by a novel coronavirus.

Non-specific symptoms of acute respiratory viral infections make it difficult for many countries without ongoing transmission of a novel coronavirus to rule out other possibilities including influenza before isolating imported febrile individuals with a possible exposure history. The incubation period helps differential diagnosis, and up to two days is suggestive of influenza. It is worth including the incubation period in the case definition of novel coronavirus infection.

Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells.

Adenovirus-mediated gene therapy shows remarkable promise as a new strategy for advanced pancreatic cancer, but satisfactory clinical results have not yet been obtained. To improve this gene therapy, we investigated the effects of gemcitabine (GEM) on transgene expression by adenoviral vectors and their biological effects. We used Ad-lacZ and adenoviral vector-expressing NK4 (Ad-NK4) as representative adenoviral vectors. These vectors express beta-galactosidase (beta-gal) and NK4 (which inhibits the invasion of cancer cells), respectively, under the control of the CMV promoter. Cells were infected with the individual adenoviruses and then treated with GEM. GEM increased beta-gal mRNA expression and beta-gal activity, and increased NK4 expression in both culture media and within infected cells, in dose-dependent manners. The increased expression of NK4 delivered by Ad-NK4 had biological effects by inhibiting the invasion of cancer cells. GEM also enhanced NK4 expression in SUIT-2 cells transfected with an NK4-expressing plasmid, suggesting that GEM enhanced CMV promoter activity. In in vivo experiments, NK4 expression within subcutaneously implanted tumors was increased in GEM-treated mice compared with control mice. These results suggest that adenovirus-mediated gene therapy with GEM may be a promising approach for treating pancreatic cancer, and that this combination therapy may decrease the risks of side effects.

Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.

Controversy exists regarding the clinical significance of S100A2 in the progression of tumours. In pancreatic cancer, little is known about the role of S100A2. The aim of this study was to clarify the clinical significance of S100A2 expression in pancreatic carcinogenesis. We microdissected invasive ductal carcinoma (IDC) cells from 22 lesions, pancreatic intraepithelial neoplasia (PanIN) cells from five lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 38 lesions, pancreatitis-affected epithelial (PAE) cells from 16 lesions, and normal ductal cells from 18 normal pancreatic tissues. S100A2 expression in 14 pancreatic cancer cell lines, microdissected cells and formalin-fixed paraffin-embedded (FFPE) samples was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Microdissection analyses revealed that IDC cells expressed higher levels of S100A2 than did IPMN, PAE or normal cells (all comparisons, p < 0.007). Cell lines from metastatic sites expressed higher levels of S100A2 than those from primary sites. PanIN cells expressed higher levels of S100A2 than normal cells (p = 0.018). IDC cells associated with poorly differentiated adenocarcinoma expressed higher levels of S100A2 than did IDC cells without poorly differentiated adenocarcinoma (p = 0.006). Analyses of FFPE samples revealed that levels of S100A2 were higher in samples from patients who survived < 1000 days after surgery than in those from patients who survived > 1000 days (p = 0.043). Immunohistochemical analysis was consistent with qRT-PCR. S100A2 may be a marker of tumour progression or prognosis in pancreatic carcinogenesis and pancreatic cancer.

Phase I/II study of irinotecan and UFT for advanced or metastatic colorectal cancer.

UNLABELLED: The aim of this study was to determine the recommended dose of irinotecan in combination with the fixed dose of oral UFT as first-line therapy in patients with advanced or recurrent colorectal cancer, and to evaluate the response rate and overall survival as a phase II study. PATIENTS AND METHODS: Thirteen patients were recruited into a phase I trial. Four doses of irinotecan ranging from 60 to 150 mg/m2/day were administered intravenously on day 1 and day 16 in combination with UFT given orally from day 2 to day 15. In a phase II study, 53 patients received at least one cycle of this therapy. RESULTS: The recommended dose of this combination was determined as irinotecan 120 mg/m2/day and UFT 400 mg/m2/day. Dose-limiting toxicities were neutropenia and prolonged leucopenia. On an intent-to-treat analysis, the response rate in the phase II study was 24.5% (95% confidence interval 13.8% to 38.2%). The median overall survival time was 20.3 months (95% confidence interval, 15.0-22.8 months). Out of 20 patients with stable disease, 17 who received more than 4 cycles of the regimen lived longer than the other 3 patients who received fewer than 3 cycles (p = 0.0353). Hematological adverse events were mainly grade 3/4 neutropenia observed in 6 out of 53 patients. Grade 3 non-hematological toxicities, such as diarrhea, anorexia, nausea/vomiting and alopecia were observed in 6 patients. CONCLUSION: Irinotecan combined with oral UFT was effective and well-tolerated. This regimen may be considered as a first-line therapy for advanced or metastatic colorectal cancer and may result in fairly long survival, even for patients with stable disease.

Propofol inhibits phorbol 12, 13-dibutyrate-induced, protein kinase C-mediated contraction of rat aortic smooth muscle.

BACKGROUND: Propofol induces dose-dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)-mediated Ca2+ sensitization plays an important role in vascular smooth muscle contraction. This study is designed to examine the effects of propofol on the active phorbol ester (phorbol 12, 13-dibutyrate; PDBu)-induced, PKC-mediated contraction of rat aortic smooth muscle. METHODS: The PDBu-induced contraction of endothelium-denuded rat aortic rings was measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or propofol, using isometric force transducers. The PDBu-induced PKC phosphorylation of endothelium-denuded rat aortic strips was detected in the presence or absence of bisindolylmaleimide I or propofol, using Western blotting. RESULTS: PDBu, but not the inactive phorbol ester, 4-alpha-phorbol 12-myristate-13-acetate, dose-dependently induced both a slowly developing sustained contraction and PKC phosphorylation of rat aortic smooth muscle, reaching the peak level at the concentration of 10(-6) M. The PDBu (10(-6) M)-induced contraction was dose-dependently inhibited by bisindolylmaleimide I with reductions of 6.8 +/- 1.8% (P > 0.05), 39.8 +/- 8.7% (P < 0.01) and 96.7 +/- 1.4% (P < 0.01) in response to concentrations of 5 x 10(-7) M, 10(-6)x M and 5 x 10(-6) M, respectively, and by propofol with decreases of 5.2 +/- 1. 6% (P > 0.05), 9.4 +/- 1.7% (P < 0.05), 65.3 +/- 9.2% (P < 0.01) and 96.2 +/- 1.6% (P < 0.01) in response to concentrations of 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M, respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu-induced increase in the density of the phosphorylated PKC bands in a dose-dependent manner, with decreases of 6.3 +/- 2.8% (P > 0.05), 42.9 +/- 3.2% (P < 0.01) and 96.6 +/- 3.4% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M or 5 x 10(-6) M bisindolylmaleimide I, respectively, and with decreases of 4.2 +/- 2.5% (P > 0.05), 13.5 +/- 1.7% (P < 0.05), 69.5 +/- 3.5% (P < 0.01) and 95.3 +/- 4.3% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M propofol, respectively. CONCLUSION: Propofol dose-dependently inhibits PDBu-induced, PKC-mediated contraction of rat aortic smooth muscle.

Sonic hedgehog is an early developmental marker of intraductal papillary mucinous neoplasms: clinical implications of mRNA levels in pancreatic juice.

Intraductal papillary mucinous neoplasms (IPMNs) are common cystic tumours of the pancreas. Sonic hedgehog (SHH) is involved in gastric epithelial differentiation and pancreatic carcinogenesis. However, a comprehensive analysis of SHH expression in IPMN has not yet been performed. In the present study, one-step quantitative real-time reverse transcription-polymerase chain reaction with gene-specific priming was used to examine mRNA levels in various types of clinical samples. SHH expression in IPMN was measured and the possible association of gastric epithelial differentiation with development of IPMN was evaluated. In bulk tissue analyses (IPMNs, 11 pancreatic cancer, and 20 normal pancreatic tissues), IPMN expressed significantly higher levels of SHH than did normal pancreas (IPMN versus normal pancreas, p = 0.0025; pancreatic cancer versus normal pancreas, p = 0.0132), but SHH expression did not differ between IPMN and pancreatic cancer (p = 0.3409). In microdissection analyses (infiltrating ductal carcinoma cells from 20 sections, IPMN cells from 20 sections, pancreatitis-affected epithelial cells from 11 sections, and normal epithelial cells from 12 sections), IPMN cells expressed significantly higher levels of SHH than did cancer cells, normal cells, or pancreatitis-affected ductal cells (all comparisons, p < 0.008). Pancreatic juice analyses (20 samples from pancreatic cancers, 31 samples from IPMNs, and 27 samples from chronic pancreatitis) revealed that SHH expression differed significantly between IPMN juice and pancreatitis juice (p < 0.0001), and between cancer juice and pancreatitis juice (p = 0.0125). Receiver operating characteristic curve analyses revealed that SHH measurement in pancreatic juice was useful for discriminating IPMN from chronic pancreatitis (area under the curve = 0.915; 95% confidence interval: 0.796-0.976). The data suggest that overexpression of SHH is an early event in the development of IPMN and that SHH measurement in pancreatic juice may provide some advantages for the treatment or follow-up of a subset of patients with IPMN or chronic pancreatitis.

Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival.

NK4 or adenovirus vector expressing NK4 (Ad-NK4) can act bifunctionally as a hepatocyte growth factor antagonist and angiogenesis inhibitor and has potential value in cancer therapy. The aim of this study was to evaluate the therapeutic efficacy of Ad-NK4 in combination with gemcitabine (GEM) against pancreatic cancer. In vitro study showed a strong antiproliferative effect of GEM and a potent anti-invasive effect of Ad-NK4 against pancreatic cancer cells. In in vivo experiments, SUIT-2 human pancreatic cancer cells were implanted into the pancreas of nude mice. Mice were treated with Ad-NK4 by injection into the peritumoral region of the pancreas on day 5 after implantation followed by weekly i.p. injections of GEM. On day 28 after implantation, pancreatic tumor volume was significantly smaller than that in mice treated with Ad-LacZ, Ad-NK4 alone, or GEM alone. Furthermore, combination therapy completely suppressed peritoneal dissemination and liver metastases, leading to significantly increased survival. Histologic and immunohistochemical assays of primary tumors indicated that combination therapy prohibited both cell proliferation and angiogenesis, resulting in high levels of apoptosis. These results suggest that peritumoral injection of Ad-NK4 plus GEM is a potent combination therapy for pancreatic cancer.

Comparison of the effects of isoflurane and sevoflurane on protein tyrosine phosphorylation-mediated vascular contraction.

BACKGROUND: Isoflurane induces greater effects on vasodilation and decreasing blood pressure than sevoflurane. Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an important role in regulating vascular smooth muscle contraction. The aim of the present study was to compare the effects of isoflurane and sevoflurane on tyrosine phosphorylation-mediated vascular constriction, by assessing the degree of sodium orthovanadate (Na(3)VO(4), tyrosine phosphatase inhibitor)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle. METHODS: Na(3)VO(4)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle were measured in the presence of genistein, a tyrosine kinase inhibitor, and different concentrations of isoflurane and sevoflurane, using isometric force measurement and Western blot, respectively. RESULTS: Na(3)VO(4) (10(-4) M) induced sustained contraction and tyrosine phosphorylation of substrates that were both markedly attenuated in the presence of genistein (5 x 10(-5) M). Isoflurane and sevoflurane dose-dependently (1, 2, 3 MAC) attenuated the Na(3)VO(4)-induced contraction (P < 0.05-0.005, n = 8), with a greater degree of inhibition by isoflurane than sevoflurane at 2 MAC (P < 0.01) and 3 MAC (P < 0.05). Both anesthetics also attenuated the total band density of the Na(3)VO(4)-induced, tyrosine-phosphorylated substrates in a concentration-dependent manner (P < 0.05-0.005, n = 4), with much greater attenuation by isoflurane than sevoflurane at 1 and 2 MAC (P < 0.05), respectively. CONCLUSION: The results of the present study demonstrate that isoflurane exhibits a greater degree of inhibition on the Na(3)VO(4)-stimulated contraction and protein tyrosine phosphorylation of rat aortic smooth muscle compared with sevoflurane. These findings suggest that isoflurane depresses the protein tyrosine phosphorylation-mediated contraction of vascular smooth muscle to a greater degree than sevoflurane.

Laparoscopic pancreatic surgery: current indications and surgical results.

BACKGROUND: Although minimally invasive surgery has achieved worldwide acceptance in various fields, laparoscopic surgery for pancreatic diseases has been reported only rarely. The purpose of this study was to evaluate the outcomes and feasibility of laparoscopic pancreatic surgery. METHODS: Fifteen patients, comprising eight men and seven women with an average age of 54 years, underwent laparoscopic pancreatic surgery. Distal pancreatectomy was indicated for solid tumors ( n = 4), cystic lesions ( n = 3), and chronic pancreatitis ( n = 2). Cystogastrostomy was performed for pseudocysts ( n = 4) and enucleation for insulinomas ( n = 2). The lesions varied in size from 1 to 9 cm (2.9 +/- 2.4 cm) and were located in the pancreatic head ( n = 2), body ( n = 3), or tail ( n = 10). For distal pancreatectomy, the splenic artery was divided and the parenchyma was transected with a linear stapler. Laparoscopic ultrasonography was used to determine the distance between the tumor and the main pancreatic duct for enucleation as well as to localize the lesion for distal pancreatectomy. Cystogastrostomy, 4.5 cm in length, was also performed with the linear stapler through the window of the lesser omentum. RESULTS: Mean operation time was 249 +/- 70 min (293 +/- 58 min in distal pancreatectomy, 185 +/- 14 min in enucleation, 204 +/- 50 min in cystogastrostomy), and mean blood loss was 138 +/- 184 g (213 +/- 227 g, 75 +/- 35 g, 38 +/- 48 g, respectively). Two distal pancreatectomies (13%) were converted to open surgery due to severe peripancreatic inflammation. There was no related mortality, but there were two cases (15%) of pancreatic fistula, one in a distal pancreatectomy case and the other in an enucleation case, and both were treated conservatively. CONCLUSIONS: Laparoscopic pancreatic surgery is safe and feasible for patients with benign tumors and cystic lesions.

Gallbladder duplication successfully removed laparoscopically using endoscopic nasobiliary tube.

Laparoscopic cholecystectomy is sometimes difficult due to complicated biliary anatomy including gallbladder duplication, a rare anomaly of the biliary tract. We report a case of duplicated gallbladder successfully removed under laparoscopy using endoscopic nasobiliary (ENB) tube cholangiography. A 61-year-old Japanese woman presented us with right upper abdominal pain. Ultrasonography revealed two cystic structures lying in the gallbladder fossa, and the upper one contained multiple stones. Endoscopic retrograde cholangiography showed two gallbladders, each of which has a cystic duct draining into the common bile duct separately. Laparoscopic cholecystectomy was planned under the preoperative diagnosis of double gallbladder with gallstones in the accessory gallbladder. The ENB tube was inserted just before the operation. Laparoscopic removal of the double gallbladder was successfully done using the ENB tube to identify the biliary tree anatomy and to close the stump of the cystic duct. In this communication, we would like to stress the usefulness of the ENB tube at the time of laparoscopic biliary surgery in patients with biliary anomalies including gallbladder duplication.

Simulated microgravity culture system for a 3-D carcinoma tissue model.

An in vitro organotypic culture model is needed to understand the complexities of carcinoma tissue consisting of carcinoma cells, stromal cells, and extracellular matrices. We developed a new in vitro model of carcinoma tissue using a rotary cell culture system with four disposable vessels (RCCS-4D) that provides a simulated microgravity condition. Solid collagen gels containing human pancreatic carcinoma NOR-P1 cells and fibroblasts or minced human pancreatic carcinoma tissue were cultured under a simulated microgravity condition or a static Ig condition for seven days. NOR-P1 cultures subjected to the simulated microgravity condition showed greater numbers of mitotic, cycling (Ki-67-positive), nuclear factor-kappa B-activating cells, and a lower number of apoptotic cells than were shown by cultures subjected to the static Ig condition. In addition, human pancreatic carcinoma specimens cultured under the simulated microgravity condition maintained the heterogeneous composition and cellular activity (determined by the cycling cell ratio and mitotic index) of the original carcinoma tissue better than static culture conditions. This new 3-D rotary cell culture system with four disposal vessels may be useful for in vitro studies of complex pancreatic carcinoma tissue.

Laparoscopic wedge resection of gastric submucosal tumors.

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinical utility of laparoscopic surgery for gastric submucosal tumor. METHODS: The records of 11 patients who underwent laparoscopic wedge resection (LR group) for gastric submucosal tumors were reviewed and compared with those of 8 patients who underwent open surgery (OS group). RESULTS: Mean operation time was 145 +/- 43 min in the LR group and 127 +/- 33 min in the OS group (p = 0.301). Mean blood loss was 97 +/- 107 and 107 +/- 47 g, respectively (p = 0.387). Patients in the LR group began walking 1.4 +/- 0.7 days after surgery, which was significantly earlier than those in the OS group (2.7 +/- 1.3 days, p = 0.021). The first flatus (1.5 +/- 0.5 vs. 3.1 +/- 0.6 days, respectively, p = 0.0004) and resumption of oral food intake (3.0 +/- 1.7 vs. 4.3 +/- 0.9 days, respectively, p = 0.020) were also earlier in the LR group. White blood cell count on the first postoperative day was lower (7,000 +/- 2,100 vs. 11,900 +/- 3,580/mm(3), respectively, p = 0.004) in the LR group than in the OS group, and the duration of fever (>38.0 degrees C; 0.1 +/- 0.3 vs. 0.9 +/- 0.8 days, respectively, p = 0.014) and the period of postoperative hospitalization (13.2 +/- 3.7 vs. 20.8 +/- 6.1 days, respectively, p = 0.014) were significantly shorter in the LR group than in the OS group. No complications occurred in either group. CONCLUSION: Laparoscopic surgery was superior to open surgery in terms of postoperative recovery time with comparable operation time and blood loss. Laparoscopic wedge resection is a promising surgical alternative for the treatment of gastric submucosal tumors.

Gallbladder torsion: case report.

Torsion of the gallbladder (GB) is a rare, acute abdominal condition. The treatment of choice is cholecystectomy. Even with recent advances in radiologic imaging modalities, it is difficult to make a correct preoperative diagnosis of GB torsion. We report a case of GB torsion with a retrospective review of the radiologic findings of magnetic resonance imaging, computed tomography, and ultrasonography. Those findings were compared with the histopathologic findings of the surgical specimen. The radiologic findings in our case were useful for making a preoperative diagnosis of GB torsion. We postulate the characteristic magnetic resonance findings and discuss discrepancies in the evaluations of the GB wall.

ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3).

p70ik3-1 (a 70-kDa protein) contains a cyclin box, and binds to p35cdk3 in vivo and in vitro [Matsuoka, M., Matsuura, Y., Semba, K. & Nishimoto, I. (2000) Biochem. Biophys. Res. Commun. 273, 442-447]. In spite of its structural similarity to cyclins, p70ik3-1 does not activate cyclin-dependent kinase 3 (cdk3)-mediated phosphorylation of pRb, histone H1, or the C-terminal domain of RNA polymerase II. Here, we report that Ser274 of p70ik3-1 is phosphorylated by cdk2 or cdk3 bound to cyclin A and to cyclin E in vitro. We also found that in COS7 cells in which cyclin E and cdk3 were ectopically overexpressed, the phosphorylation level of Ser274 in coexpressed p70ik3-1 is upregulated. We therefore conclude that p70ik3-1 is a substrate for cdk3-mediated phosphorylation.

Laparoscopically assisted resection of choledochal cyst and Roux-en-Y reconstruction.

UNLABELLED: Laparoscopic surgery for a congenital choledochal cyst was accomplished in five of eight adult patients for whom it was attempted (63%). Creation of a Roux-en-Y jejunal limb by midline minilaparotomy and hepaticojejunostomy using a laparoscopic sewing instrument facilitated the procedure. BACKGROUND: Congenital choledochal cyst is a good indication for laparoscopic surgery. However, only two case reports are available at this writing. METHODS: Eight adult patients, ages 19 to 61 years (mean, 32.6 years), underwent laparoscopically assisted resection of the choledochal cyst and Roux-en-Y hepaticojejunostomy. RESULTS: The whole procedure was accomplished in five patients (63%). The duration of the procedure ranged from 525 to 680 min (average, 616 min). Open conversion in three patients was necessitated by severance of a small common hepatic duct because of disorientation caused by previous laparoscopic cholecystectomy, electrocautery injury to the common channel distal to the anomalous pancreaticobiliary junction, or heavy adhesion around the cyst secondary to recent severe cholangitis. Creation of a Roux-en-Y jejunal limb by midline minilaparotomy and hepaticojejunostomy using a laparoscopic sewing instrument facilitated the procedure. CONCLUSIONS: Laparoscopically assisted resection of the choledochal cyst and hepaticojejunostomy are technically feasible and deserve further clinical trials.