Mirizzi syndrome: noteworthy aspects of a retrospective study in one centre

BACKGROUND: Mirizzi syndrome is uncommon. It is, however, clinically important, as it is associated with an increased incidence of bile duct injury and demands more complex surgical techniques. METHODS: A retrospective review of 24 consecutive cases of Mirizzi syndrome that arose between January 1997 and July 2002 was performed. A total of 1881 cholecystectomies were performed during that period. RESULTS: Of the 24 patients, 19 (79.2%) had Mirizzi type I, four (16.7%) had type II, while one (4.2%) had type III disease. Only 54.2% of patients were symptomatic prior to presentation. One-third of patients had normal liver function tests. Ultrasonography and computed tomography were not helpful in diagnosing this entity. Endoscopic retrograde cholangiopancreatography (ERCP) was useful to identify cholecystocholedochal fistulas and to allow therapeutic endoscopic stenting but failed to pick up the syndrome in half of the patients. Inadvertent bile duct injury occurred in four patients (16.7%), all occurred in patients without a preoperative diagnosis. Three of the four injuries occurred during operations by a senior registrar rather than a consultant. Mirizzi type I was managed with either total or subtotal cholecystectomy, while types II and III cases were managed with either T-tube insertion or biliary bypass procedures. Bile duct injury was managed with T-tube successfully in one patient while the rest went on to biliary bypass operations. All except one patient had good functional outcomes on follow up. CONCLUSION: The preoperative diagnosis of Mirizzi syndrome is a challenge. Only constant vigilance during intraoperative dissection of the Calot's triangle will reduce the incidence of bile duct injury in Mirizzi syndrome that can occur in both open and laparoscopic surgery.     

Adult intussusception: experience in Singapore

Introduction: Gastrointestinal intussusception is an uncommon clinical entity in adults and is interestingly distinct from its paediatric form. In adults an identifiable lead lesion is found in the majority of cases, of which a significant percentage are malignant. Its treatment is thus different from that of paediatric intussusception. The present study reviews our experience of treating adult intussusception. Methods: A retrospective review of patients with a postoperative diagnosis of gastrointestinal intussusception between January 1997 and December 2002 was conducted. All patients under the age of 18 and cases of rectal prolapse were excluded. Results: During the 5‐year period, there were nine cases of intussusception. There were four male and five female patients, with a mean age of 63.8 years (range 37?85 years). Less than half of the patients (44.4%) presented with acute symptoms. The most common symptoms were abdominal pain and distension. The symptoms were intermittent in 77.8% (7 of 9) of patients. Only two patients had a palpable abdominal mass, while another had signs of acute intestinal obstruction. Computed tomography was the most useful imaging modality, identifying intussusception in six out of six patients. Eight patients had lead lesions occurring at the ileocaecal junction resulting in ileo‐colonic intussusception. Of these eight, four were malignant (two adenocarcinomas and two lymphomas). There was one sigmoid‐rectal intussusception secondary to adenocarcinoma. All patients were treated operatively. Seven patients were treated with en bloc resection. Conclusion: Although uncommon, surgeons need to be aware of the epidemiology and treatment options for adult intussusception. The symptoms and signs are often non‐specific and the surgeon might be faced with the diagnosis only at laparotomy. Computed tomography is the most useful imaging modality. An identifiable organic lesion is present in most cases, of which more than 50% are malignant (especially in the large bowel). Operative treatment is thus prudent. En bloc resection is recommended for ileo‐colonic and colo‐colonic intussusception. There is, however, a role of initial reduction in selected patients with ileo‐ileal intussusception.     

抗肌萎缩蛋白小基因对Duchenne肌营养不良病理改变的治疗作用

目的　探讨Duchenne肌营养不良 (DMD)的病理变化和治疗方法。方法　采用重组腺相关病毒载体 (rAAV)介导的人抗肌萎缩蛋白小基因 (SMCKA3999)观察DMD的病理改变和治疗作用。将抗肌萎缩蛋白小基因SMCKA3999克隆至rAAV并包装成rAAVSMCKA3999病毒 ,将 5× 10 9病毒颗粒分多点注射于DMD模型鼠mdx腓肠肌 ,4个月后取局部肌组织 ,分别采用免疫荧光、埃文斯氏蓝染料、电镜等方法 ,观察rAAVSMCKA3999对DMD病理改变的治疗作用。结果　rAAVSMCKA3999有效稳定表达并使肌膜缺失的抗肌萎缩蛋白恢复 ,明显改善DMD肌肉病理改变。结论　rAAVSMCKA3999能显著改善mdx小鼠骨骼肌病理变化 ,有希望成为Duchenne肌营养不良有效的生物治疗药物     

Up-regulation of inhibitory natural killer receptors CD94/NKG2A with suppressed intracellular perforin expression of tumor-infiltrating CD8+ T lymphocytes in human cervical carcinoma

Inhibitory signals that govern the cytolytic functions of CD8(+) T lymphocytes have been linked to the expression of natural killer cell receptors (NKRs) on CTLs. There is limited knowledge about the induction of inhibitory NKR (iNKR) expression in vivo. Up-regulation of iNKRs has been linked to the modulation of the virus- and/or tumor-specific immune responses in animal models. In the present study, we directly examined the expression of various NKRs on tumor-infiltrating lymphocytes (TILs) derived from human cervical cancer. We found that in human cervical cancer, the percentage expression of immunoglobulin-like NKR(+)CD8(+) T lymphocytes were similar in gated CD8(+)-autologous TILs and peripheral blood mononuclear cells. On the contrary, cervical cancer-infiltrating CD8(+) T lymphocytes expressed up-regulated C-type lectin NKRs CD94/NKG2A compared with either peripheral blood CD8(+) T cells or normal cervix-infiltrating CD8(+) T lymphocytes. Dual NKR coexpression analyses showed that CD94 and NKG2A were mainly expressed on CD56(-)CD161(-)CD8(+) TILs within the cancer milieu. Immunohistochemical study showed that cervical cancer cells expressed abundant interleukin 15 (IL-15) and transforming growth factor-beta (TGF-beta). In kinetic coculture assay, cervical cancer cells can promote the expression of CD94/NKG2A on CD8(+) T lymphocytes. The cancer-derived effects can be reversed by addition of rIL-15Ralpha/Fc and anti-TGF-beta antibody. Functional analyses illustrated that intracellular perforin expression of CD8(+) T cells was minimal upon up-regulation of CD94/NKG2A. Kinetic cytotoxicity assays showed that up-regulated expressions of CD94/NKG2A restrain CD8(+) T lymphocyte cytotoxicity. Our study strongly indicated that cervical cancer cells could promote the expression of iNKRs via an IL-15- and possibly TGF-beta-mediated mechanism and abrogate the antitumor cytotoxicity of TILs.     

抗血小板治疗对脑梗死患者血小板活化标记物表达的影响

目的:探讨急性脑梗死患者血小板活化状态及抗血小板药物阿司匹林和氯吡格雷治疗对血小板活化状态的影响, 为急性脑血管病的预防和治疗提供可靠的理论依据. 方法:采用流式细胞检测方法,对急性脑梗死血小板活化标记物P选择素(CD62P)及PAC-1进行检测研究. 结果:急性脑梗死患者血小板活化标记物表达明显高于正常对照组,脑梗死伴糖尿病及高血压者血小板活化标记物表达明显高于单纯脑梗死组,阿司匹林及氯吡格雷治疗能明显抑制血小板活化标记物表达,但二者在治疗后相比较无统计学差异. 结论:急性脑梗死疾病发生过程中,血小板活化起了主要作用,且高血压及糖尿病有促进体内血小板活化的作用,加重脑血管病的发生,阿司匹林及氯吡格雷在治疗急性脑梗死中能明显抑制血小板活化,在一定程度上阻断血小板活化过程,预防复发.     

Characterization of a porcine CD1-specific mAb that distinguishes CD4/CD8 double-positive thymic from peripheral T lymphocytes

Porcine peripheral T-cells bear CD4 and CD8 cell surface antigens that distinguish helper from cytotoxic T-cells. In distinction from what has been found in other species, a large percentage of peripheral T-cells simultaneously express both CD4 and CD8. Monoclonal antibody 76-7-4 was found to stain all cortical and 7 +/- 3% of medullary thymocytes, Ia+ epidermal cells (i.e. Langerhans cells), no peripheral T-cells and 50% of peripheral B-cells. The antigen detected appears analogous to human CD1. All cortical thymocytes were also stained with CD4 and CD8 mAb. Since 76-7-4 did not stain peripheral T-cells, we conclude that CD4/CD8 dual-expressing peripheral T-cells are not simply immature thymic emigrants.     

Presence of restricted killer immunoglobulin-like receptor repertoire and monoclonal T-cell receptor gamma rearrangement as evidence of mixed NK/T-cell differentiation in a subset of sinonasal lymphomas

Most sinonasal lymphomas have a restricted killer immunoglobulin-like receptor (KIR) repertoire without a monoclonal T-cell receptor-gamma (TCR-gamma) rearrangement, implying an NK lineage. However, the lineage assignment of sinonasal lymphoma with a monoclonal TCR-gamma rearrangement is unclear because of its mixed NK/T phenotype. The possibility of a mixed NK/T lineage arises with the discovery of T cells with NK features, such as KIR(+) T cells or Valpha24(+) NKT cells. The former might transform into a T-cell lymphoma with both a monoclonal TCR-gamma rearrangement and a restricted KIR repertoire; the latter might give rise to a T-cell lymphoma with a monoclonal Valpha24 rearrangement and possibly a restricted KIR repertoire. To identify such mixed-lineage lymphomas, we undertook a survey of 15 consecutive sinonasal lymphomas and found six with both a restricted KIR repertoire and a monoclonal TCR-gamma rearrangement, consistent with KIR(+) T-cell lymphomas. Among these six cases, four female CD56(-)/CD44(-)/CD8(-)/CD45RO(+)/CD45RA(-) cases constituted a distinct group with a better prognosis than the rest of the male cases of sinonasal lymphomas. None of the six cases had a monoclonal Valpha24 repertoire, thus excluding a derivation from NKT cells. The predominance of KIR(+) T cells that normally function in chronic viral infections over Valpha24(+) NKT cells that typically recognize glycolipid antigens is consistent with the known association of Epstein-Barr virus infection with sinonasal lymphoma. The demonstration of mixed lineage in a mature lymphoid neoplasm is unusual and echoes the World Health Organization classification that placed NK-cell and T-cell lymphomas in a mixed group.     

Association of Walking with Survival and RRT Among Patients with CKD Stages 3–5

Background and objectives

Patients with CKD can benefit from an increase in physical activity. Walking is one of the most common exercises in patients with CKD; however, the association of walking with outcomes in patients with CKD is not clear. This study investigated the association of walking with overall mortality and RRT in patients with CKD stages 3–5.

Design, setting, participants, & measurements

All patients with CKD stages 3–5 in the CKD program of China Medical University Hospital from June 2003 to May 2013 were enrolled. The risks of overall mortality and RRT were analyzed using competing-risks regressions.

Results

A total of 6363 patients (average age, 70 years) during a median of 1.3 (range=0.6–2.5) years of follow-up were analyzed. There were 1341 (21.1%) patients who reported walking as their most common form of exercise. The incidence density rate of overall mortality was 2.7 per 100 person-years for walking patients and 5.4 for nonwalking ones. The incidence density rate of RRT was 22 per 100 person-years for walking patients and 32.9 for nonwalking ones. Walking, independent of patients’ age, renal function, and comorbidity, was linked to lower overall mortality and lower RRT risk in the multivariate competing-risks regression. The adjusted subdistribution hazard ratio (SHR) of walking was 0.67 (95% confidence interval [95% CI], 0.53 to 0.84; P<0.001) for overall mortality and 0.79 (95% CI, 0.73 to 0.85; P<0.001) for the risk of RRT. The SHRs of overall mortality were 0.83, 0.72, 0.42, and 0.41 for patients walking 1–2, 3–4, 5–6, and ≥7 times per week, and the SHRs of RRT were 0.81, 0.73, 0.57, and 0.56, respectively.

Conclusions

Walking is the most popular form of exercise in patients with CKD and is associated with lower risks of overall mortality and RRT. The benefit of walking is independent of patients’ age, renal function, and comorbidity.