Predictors of postoperative early recurrence of extrahepatic bile duct cancer

Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer. Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6 months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared. Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1 year, p < 0.01, respectively). Multivariate analysis showed that age > 75 years, serum CA19-9 > 1008 U/ml and perineural invasion were independent predictors of early recurrence. High serum CA19-9 values (> 1008 U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.     

Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats

OBJECTIVES: The aim of this study was to document the effects of a new sedative agent, dexmedetomidine, on the mortality rate and inflammatory responses to endotoxin-induced shock in rats. DESIGN: Randomized laboratory study. SETTING: University experimental laboratory. SUBJECTS: Fifty-seven male rats. INTERVENTIONS: The animals were randomly assigned to one of four groups. The endotoxemic group (n = 16) received intravenous Escherichia coli endotoxin (15 mg/kg over 2 mins). The saline control group (n = 10) was given saline alone. The dexmedetomidine alone group (n = 15) was treated identically to the control group but also received dexmedetomidine (infusion at 5 microg.kg(-1).hr(-1)) immediately after the injection of 0.9% saline. The dexmedetomidine-endotoxin group (n = 16) was treated identically to the endotoxemic group with the additional administration of dexmedetomidine (infusion at 5 microg.kg(-1).hr(-1)) immediately after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and arterial blood gases were recorded and plasma cytokine concentrations measured during the observation. The mortality rate was assessed up to 8 hrs after endotoxin or saline injection. In addition, microscopic findings of lung tissue for each group were obtained at necropsy. Mortality rates 8 hrs after endotoxin injection were 94%, 10%, 0%, and 44% for the endotoxemic, saline control, dexmedetomidine alone, and dexmedetomidine-endotoxin groups, respectively. Hypotension and increases in plasma cytokine (tumor necrosis factor-alpha and interleukin-6) concentrations and infiltration of neutrophils in the airspace or vessel walls of the lungs were less in the dexmedetomidine-endotoxin group than in the endotoxemic group. CONCLUSIONS: Dexmedetomidine reduced mortality rate and had an inhibitory effect on inflammatory response during endotoxemia. These findings suggest that dexmedetomidine administration may inhibit the inflammatory response.     

Attitudes toward the performance of bystander cardiopulmonary resuscitation in Japan

BACKGROUND: Early initiation of bystander cardiopulmonary resuscitation (CPR) improves the chances of successful resuscitation and survival. The importance of bystander CPR is attracting more interest, and there has been an increase in attendance at CPR training courses in Japan. However, there have been few reports regarding Japanese attitudes toward the performance of bystander CPR. The present study was performed to identify current Japanese attitudes toward bystander CPR compared to our previous study performed in 1998. METHODS AND RESULTS: Between February and March 2006, participants were asked about their willingness to perform CPR in five varying scenarios, i.e., performing CPR on a stranger, a trauma patient, a child, an elderly person, and a relative, and CPR techniques consisting of chest compression plus mouth-to-mouth ventilation (CC plus MMV) versus chest compression only (CC only). A total of 4223 individuals (male 50%) completed the questionnaire, including high school students, teachers, emergency medical technicians (EMTs), medical nurses, and medical students. About 70% of the subjects had experienced CPR training more than once. Only 10-30% of high school students, teachers, and health care providers reported willingness to perform CC plus MMV, especially on a stranger or trauma victim. In contrast, 70-100% of these subjects reported willingness to perform CC only, which was the same as in our previous study. The reasons for the unwillingness among laypeople to perform CC plus MMV were inadequate knowledge and/or doubt regarding whether they could perform the techniques effectively, while health care providers reported a fear contracting of a disease. CONCLUSIONS: Most laypeople and health care providers are unlikely to perform CC plus MMV, especially on a stranger or trauma victim, but are more likely to perform CC only, as also found in our previous study in 1998. These findings suggest that MMV training should be de-emphasised and the awareness of CC alone should be emphasised because, for whatever reason, people do not want to perform MMV.     

Endoscopy in the diagnosis of small intestinal tumors

The importance of endoscopy in the diagnosis of small intestinal tumors was evaluated in 15 patients with small intestinal tumors treated in our hospital. Two tumors were benign, and 13 were malignant (carcinoma in 5 patients, malignant lymphoma in 5 and leiomyosarcoma in 3). The presence of lesions could be determined by X-rays before surgery, but definitive diagnoses were difficult. When preoperative endoscopy of the small intestine was possible accurate preoperative diagnoses could be made based on the endoscopic findings and biopsies taken under direct vision. Endoscopy is therefore very important for the diagnosis of small intestinal tumors. It is necessary to develop small intestinal endoscopes that are easier to insert.     

Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma

BackgroundThe primary objective of this phase I, open-label trial was to assess safety and tolerability of tremelimumab monotherapy and combination therapy with durvalumab in Japanese patients with advanced cancer. Tremelimumab is a fully human monoclonal antibody against CTLA-4 in clinical trials; durvalumab is a monoclonal antibody against PD-L1 for the treatment of bladder and lung cancer.MethodsIn part 1, tremelimumab 3 or 10 mg/kg was given every 4 weeks (Q4W) for 6 doses, and thereafter every 12 weeks until discontinuation (n = 8); subsequently tremelimumab 10 mg/kg Q4W for 6 doses/Q12W and thereafter until discontinuation was administered in 41 patients with malignant pleural or peritoneal mesothelioma (MPM). In part 2, tremelimumab 10 mg/kg (Q4W for 6 doses followed by Q12W for 3 doses) was given in combination with durvalumab 15 mg/kg (Q4W for 13 doses) in cohort 1 (n = 4). In cohort 2 (n = 6), tremelimumab 1 mg/kg (Q4W for 4 doses) was given in combination with durvalumab 20 mg/kg (Q4W for 4 doses followed by 10 mg/kg Q2W for 22 doses), while in cohort 3 (n = 6), fixed-dose tremelimumab 75 mg Q4W for 4 doses plus durvalumab 1500 mg Q4W for 13 doses was given.ResultsIn part 1, no dose-limiting toxicities (DLTs) for tremelimumab 3 or 10 mg/kg (Q4W for 6 doses/Q12W thereafter until discontinuation) were observed. Six (75%) patients reported treatment-related adverse events (trAEs). In the MPM dose-expansion cohort, 38 (92.7%) patients reported trAEs. In part 2, one DLT (Grade 4 myasthenia gravis) was reported for tremelimumab 10 mg/kg (Q4W for 6 doses/Q12W for 3 doses) plus durvalumab 15 mg/kg (Q4W for 13 doses). One DLT (Grade 4 hyperglycemia) was reported for tremelimumab 75 mg (Q4W for 4 doses) plus durvalumab 1500 mg (Q4W for 13 doses). Fourteen (87.5%) patients reported trAEs. Tremelimumab demonstrated low immunogenicity; 1 (16.7%) patient developed antidrug antibodies.ConclusionTremelimumab 10 mg/kg (Q4W/Q12W), tremelimumab 1 mg/kg (Q4W) plus durvalumab 20 mg/kg (Q4W/10 mg/kg Q2W), and fixed-dose tremelimumab 75 mg (Q4W) plus durvalumab 1500 mg (Q4W) were safe and tolerable.ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02141347","term_id":"NCT02141347"}}NCT02141347 (https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02141347","term_id":"NCT02141347"}}NCT02141347)