如何改善靶向药物在胆管癌中的疗效？

10年中胆管癌(CC)的处理方法已经有了巨大的改变.仅仅在几年前,胆管癌晚期患者还没有效的治疗方案,只有支持治疗.并且在没有有效证据及随机研究结果的情况下,常给予患者姑息化疗. 根据两个随机试验的结果已经建立了一个新的治疗标准:吉西他滨和铂化合物的联合化疗方案已被证明能显著延长胆道肿瘤不能手术切除的患者的生存期[1-2].此外,新治疗方式的发展,包括具有开拓性的靶向性治疗也正开辟治疗CC的新途径[3].毫无疑问,考虑如何针对不同肿瘤类型使用新制剂治疗是个合乎时机的研究主题.一些Ⅱ期靶向药物研究,主要是抗-EGFR和VEGF药物,但是结果仍不明确.     

Adefovir treatment for chronic hepatitis B in heart transplant recipients

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice‐monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV‐DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild‐to‐moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV‐DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV‐DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine‐resistant chronic hepatitis B.     

Prevention of Anastomotic Leakage after Total Gastrectomy with Perioperative Supplemental Oxygen Administration: A Prospective Randomized, Double-blind, Controlled, Single-center Trial

Background

The role of supplemental oxygen therapy in the healing of esophagojejunal anastomosis is still very much in an experimental stage. The aim of the present prospective, randomized study was to assess the effect of administration of perioperative supplemental oxygen therapy on esophagojejunal anastomosis, where the risk of leakage is high.

Methods

We enrolled 171 patients between January 2009 and April 2012 who underwent elective open esophagojejunal anastomosis for gastric cancer. Patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO₂) of 30 % (n = 85) or 80 % (n = 86). Administration commenced after induction of anesthesia and was maintained for 6 h after surgery.

Results

The overall anastomotic leak rate was 14.6 % (25 of 171): 17 patients (20 %) had an anastomotic dehiscence in the 30 % FiO₂ group and 8 (9.3 %) in the 80 % FiO₂ group (P < 0.05). The risk of anastomotic leak was 49 % lower in the 80 % FiO₂ group (relative risk 0.61; 95 % confidence interval 0.40–0.95) versus 30 % FiO₂.

Conclusions

Supplemental 80 % FiO₂ provided during and for 6 h after major gastric cancer surgery to reduce postoperative anastomotic dehiscence should be considered part of ongoing quality improvement activities related to surgical care, with few risks to the patient and little associated cost.     

Sentinel node mapping in high risk endometrial cancer after laparoscopic supracervical hysterectomy with morcellation

INTRODUCTIONOccult endometrial cancer after supracervical hysterectomy is very uncommon. Even if optimal management of those rare cases is still unproven, to guide the need for further therapies, restaging should be recommended in this situation.PRESENTATION OF CASEWe report of a 60-year old woman with occult high risk endometrial cancer after supracervical hysterectomy with morcellation. We describe the feasibility of laparoscopic intraoperative sentinel node identification with cervical stump removing to restage the suspicious early stage high risk endometrial cancer.DISCUSSIONIn high risk endometrial cancer surgical restaging is important, considering that 10–35% of cases can present pelvic nodal metastasis. To reduce the treatment related morbidity maintaining the benefit of surgical staging, with a negative preoperative PET/CT, we performed a laparoscopic SN mapping with cervical stump removing.CONCLUSIONThis report highlight the fact that SN mapping with cervical injection is a feasible and safe technique also without the uterine corpus after supracervical hysterectomy with morcellation.     

Subependymal nodules and giant cell tumours in tuberous sclerosis complex patients: prevalence on MRI in relation to gene mutation

Purpose

The purpose of this study was to estimate the association among the presence of subependymal nodules (SENs), subependymal giant cell tumours (SGCTs) and gene mutation in tuberous sclerosis complex (TSC) patients.

Methods

Clinical records and images of 81 TSC patients were retrospectively reviewed by two neuroradiologists in consensus. All patients were assessed for gene mutations and were categorized as TSC1 or TSC2 mutation carriers, or no-mutations-identified (NMI) patients. They underwent a brain magnetic resonance imaging (MRI) using 0.1 mmol/kg of gadobutrol. Any enhancing SEN?≥?1 cm and placed near the foramen of Monro was considered SGCT. Two MRI follow-up exams for each patient with SGCT were evaluated to assess tumour growth using Wilcoxon and chi-squared tests.

Results

Of 81 patients, 44 (54 %) were TSC2 mutation carriers, 20 (25 %) TSC1 and 17 (21 %) NMI. Nine (11 %) had a unilateral and three (4 %) a bilateral SGCT. Fifty of 81 patients (62 %) showed at least one SEN. None of the 31 patients without SEN showed SGCTs, whilst 12 (24 %) of the 50 patients with at least one SEN showed SGCTs (p?=?0.003). The association between the presence of SGCT or SEN and gene mutation was not significant (p?=?0.251 and p?=?0.187, respectively). At follow-up, the median SGCT diameter increased from 14 to 15 mm (p?=?0.017), whilst the median SGCT volume increased from 589 to 791 mm³ (p?=?0.006).

Conclusions

TSC patients with SENs are more likely to present with SGCT than those without SENs, in particular for TSC2 mutation carriers. The SGCT growth rate may be missed if based on the diameter instead of on the volume.     

White matter abnormalities in Parkinson's disease patients with glucocerebrosidase gene mutations

Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinson's disease. This study investigated brain alterations in Parkinson's disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinson's disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age‐ and sex‐matched healthy controls and 14 idiopathic Parkinson's disease patients without glucocerebrosidase gene mutations were also studied. Tract‐based spatial statistics was used to perform a white matter voxel‐wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel‐based morphometry was used to assess gray‐matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinson's disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinson's disease patients with no mutations. No white matter abnormalities were found in Parkinson's disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinson's disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinson's disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment. © 2013 Movement Disorder Society