Mirizzi's syndrome: diagnostic and surgical considerations in 25 patients

Mirizzi's syndrome is a rare complication of long-standing cholelithiasis. Many surgical approaches of varying complexity have been advocated for treatment. However, the distorted extrahepatic biliary anatomy continues to be threatening, with a high risk of biliary complications. Presented here is a series of 25 patients with Mirizzi's syndrome who were treated at the Dokuz Eylul University Hospital since 1985. Type I lesion (without cholecystocholedochal fistula) was encountered in 11 patients, while the remaining 14 had type II lesions (with cholecystocholedochal fistula). Preoperative diagnoses were made in 14 of the 25 patients (56%). Follow-up in 17 patients ranged from 1 to 96 months (mean, 40 months). Unfortunately, the remaining 8 patients were lost to follow-up after discharge. The morbidity rate in our series was 32%, while no mortality was encountered. During long-term follow-up, no biliary stricture was diagnosed. Following an uneventful postoperative course, all of our patients are symptom-free and doing well, with normal liver function. We conclude that partial cholecystectomy alone is a safe and sound surgical approach for the treatment of type I lesions. For type II lesions, depending on the size of the fistula, either primary closure over a T-tube, or bilio-digestive anastomosis, preferably Roux-en-Y, can be an appropriate treatment modality, with a low morbidity rate. Received for publication on Feb. 16, 1999; accepted on July 12, 1999     

Clinical and ethical considerations in lung transplantation surgery in patients with post-COVID pulmonary fibrosis

Back in December 2019 a novel strain virus called, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or later called Corona Virus Disease 2019 (COVID...     

Prevention of antibody-mediated kidney transplant rejection

There is increasing evidence that antibody-mediated rejection is the major cause of late kidney graft failure. Prevention of antibody-mediated allograft damage has therefore become an important issue in kidney transplantation. Such prevention starts already before transplantation with the avoidance of sensitizing events. When a patient is already sensitized, precise characterization of alloantibodies and exact HLA typing of the donor at the time of transplantation are mandatory. To ensure timely and successful transplantation of highly sensitized patients, desensitization, and inclusion in special programs such as the Eurotransplant Acceptable Mismatch Program should be considered. After transplantation, close monitoring of kidney function, testing for the de novo development or changing characteristics of alloantibodies, and attention to non-adherence to immunosuppression is obligatory. In the current overview, we discuss the currently available measures for the prevention of antibody-mediated kidney graft rejection.     

Immunogenetic considerations in islet transplantation: The role of Ia antigens in graft rejection

As demonstrated by Faustman et al., islets that are pretreated with Ia antibodies and complement show markedly prolonged survival as compared with islets, with the same immunogenetic disparity, without antibody pretreatment. In order to test whether it is simply the absence of an allo-Ia disparity that accounts for this finding, we have transplanted islets across class I disparities alone; in certain cases, such islets are rapidly rejected. Yet, even though there is no allo-Ia difference on such islets, pretreatment of the islets with anti-Ia monoclonal antibody also results in markedly prolonged survival. We suggest that the presence of Ia antigens may serve as a differentiation marker for cells that can present class I antigens in an immunogenic manner; further, allo-Ia antigens can lead to a stronger anti-class I rejection response.     

Ulcerative colitis: immune function, tissue fibrosis and current therapeutic considerations

Background  

Ulcerative colitis (UC) is a complex disease in which the interaction of genetic, environmental and microbial factors drives chronic intestinal inflammation that finally leads to extensive tissue fibrosis.     

Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes.

BACKGROUND: Information concerning long-term operative outcomes in patients with cystic fibrosis (CF) is relatively sparse in the operative literature. METHODS: A retrospective review of CF patients with operative conditions was performed (1972-2004) at a tertiary children's hospital to analyze outcomes including long-term morbidity and survival. RESULTS: A total of 226 patients with CF presented with an operative diagnosis (113 men, 113 women). A total of 422 operations were performed in 213 patients (94%). The mean age at operation was 4.1 +/- 6.2 years (range, 1 d to 26 y) and 109 were neonates. Fifteen of 42 (36%) babies with simple meconium ileus (MI) were treated nonoperatively with hypertonic enemas, 27 of 42 and all 45 patients with complicated MI required operation, including 15 with jejunoileal atresia (17%). Seventeen of 27 (63%) patients with meconium ileus equivalent had MI as neonates; 7 of 27 (26%) required operation. Eight of 9 (89%) with fibrosing colonopathy required operation. Organ transplantation was required in 21 patients. Follow-up evaluation was possible in 204 of 213 (96%) patients. The duration of follow-up evaluation was 14.9 +/- 8.5 years (range, 2 mo to 35 y). Operative morbidity was 11% at 1 year, 2% at 2 to 4 years, 1% at 5 to 10 years, and less than 1% at more than 10 years. There were 24 deaths (11%); 22 followed CF-related pulmonary complications and included 8 of 16 (50%) children with pneumothorax. CONCLUSIONS: Long-term survival in CF patients has improved significantly (89%), with many surviving into the fourth decade. MI may predispose to late complications including meconium ileus equivalent and fibrosing colonopathy. Pneumothorax in CF patients is an ominous predictor of mortality. Children with CF are living longer and are good candidates for operation, but require long-term follow-up evaluation because of ongoing exocrine dysfunction.     

Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents

Renal fibrogenesis can be induced by several injury mechanisms in different renal diseases, but ultimately produces identical fibrotic changes in the kidney. Recently, a number of agents that can inhibit extracellular matrix (ECM) accumulation have been studied, suggesting a therapeutic utility in the treatment of fibrotic renal disease. Pirfenidone (PFD) is a small molecule that has shown efficacy in various models of renal damage with progressive disease. The apparent absence of toxicity in PFD suggests that it does not affect the normal ECM turnover. Relaxin, a hormone belonging to the insulin-like growth factor (IGF) family, has antifibrotic properties and has been used for a long time to induce transient remissions in patients with scleroderma. Only recently it has been shown to drastically reduce corticomedular scarring in animal models. Bone morphogenetic protein 7 (BMP-7), a member of the transforming growth factor beta (TGF-beta) superfamily, has been shown to reduce glomerular and interstitial area, and prevent glomerular sclerosis even more effectively than enalapril. Finally, hepatocyte growth factor (HGF), with its multiple biological activities on a wide variety of cells, has an organotrophic role in the regeneration and protection of various organs including the kidney. Both endogenous and exogenous HGF have shown suppressive effects on renal fibrosis and chronic renal damage in various animal models. The inhibition of pathological ECM accumulation and the modulation of fibrotic mechanisms with these new antifibrotic agents is an achievable goal and could confer further benefits beyond the current therapies used in the treatment of chronic renal diseases.     

Anesthetic considerations in diabetic patients. Part I: preoperative considerations of patients with diabetes mellitus

Some studies have reported that tight glycemic control in diabetic patients undergoing major surgery improves perioperative morbidity and mortality rates. Recently, however, large randomized studies have shown such control increases the mortality rate, since aggressive glycemic control induces more frequent incidences of hypoglycemia. Diabetic patients have cerebral complications during the perioperative period more often than their nondiabetic counterparts. Further, anesthetic agents have some effects on cerebral circulation and cerebrovascular carbon dioxide reactivity. Hence, anesthesiologists should have adequate knowledge about anesthetic agents that maintain the integrity of the cerebral circulation. Patients with diabetes mellitus (DM) have an increased susceptibility to perioperative infections. Recent work confirmed that a combination of intravenous and subcutaneous insulin as a glucose management strategy had beneficial effects identical with intravenous insulin therapy alone on the reduction of infection rates during the postoperative period.     

Endocarditis in burn patients: clinical and diagnostic considerations

BACKGROUND: Burned patients are at high risk for invasive procedures, bacteremia, and other infectious complications. Previous publications describe high incidence, delayed diagnosis, and high mortality for endocarditis in burned patients, but do not address use of contemporary diagnostic criteria. Further analysis of the clinical presentation and diagnosis may aid in the earlier recognition and decreased mortality of endocarditis in burned patients. METHODS: At a 40 bed burn center, during the period from 1 January 2003 to 1 August 2006, blood culture, electronic inpatient, echocardiographic, and autopsy records were reviewed for cases of endocarditis and persistent bacteremia (blood culture positivity for the same organism separated by 24h). In addition, we reviewed cases of burn-related bacterial endocarditis published in the English language. We compared the clinical and diagnostic aspects of our identified cases with those in the published literature. RESULTS: There were 90 episodes of persistent bacteremia or fungemia in 56 of 1250 patients admitted during the study period. Echocardiography was performed on 19, identifying 4 cases of endocarditis. One additional case of endocarditis was identified post-mortem. Time until echocardiography ranged from 6 to 176 days after onset of bacteremia. Case patient age ranged from 31 to 64 years, and total burn surface area ranged from 34 to 80%. Endocarditis occurred in 0.4% of burn unit admissions and in 8.9% of these patients with persistent bacteremia. Sites involved included the mitral valve (3), tricuspid valve (2), aortic valve (1), and pulmonic valve (1). Pathogens included Staphylococcus aureus, Pseudomonas aeruginosa, and one case of Enterococcus faecium. Diagnostic clues were minimal. Case mortality was 100%. A literature review revealed 17 publications describing confirmed bacterial endocarditis in burned patients. These cases revealed a predilection for infection by S. aureus and P. aeruginosa, a relative paucity of diagnostic clues prior to death, and a trend towards ante-mortem diagnosis and increased survival with use of diagnostic echocardiography. CONCLUSIONS: The incidence and mortality of endocarditis in burned patients remain high. Clinical clues for endocarditis in this cohort are minimal and diagnosis may be delayed. For burned patients with persistent bacteremia, especially S. aureus or P. aeruginosa of unknown source, the diagnosis of endocarditis should be entertained and early echocardiography considered.     

预防预致敏受者尸体肾移植术后急性排斥反应的临床研究

目的 探讨HLA配型及新型免疫抑制剂治疗方案对预防致敏患者肾移植术后急性排斥反应的影响.方法 实验组选择46例术前致敏患者(术前PRA>10%),对照组选择同期705例未致敏患者(术前PRA<10%),实验组患者均采用诱导治疗(ATG 100 mg/d,5～7 d)+三联免疫抑制剂维持治疗方案(FK506+MMF+激素),比较两组间患者术后急性排斥反应发病率、移植肾功能延迟恢复比例、移植肾/患者一年存活率,同时分析HLA配型对移植肾急性排斥反应的影响.结果 实验组与对照组急性排斥反应的发病率分别为30.43%和19.57%(P<0.05);移植肾功能延迟恢复发病率分别为60.86%和11.87%(P<0.01).患者一年存活率分别为95.65%和98.44%,一年移植肾存活率分别为93.48%和96.88%;一年时平均血肌肝分别为130 mmol/dL和125 mmol/dL,差异无统计学意义.实验组患者HLA相配率(4.2)明显高于对照组患者(2.8)(P<0.05).实验组中HLA配型2-4错配的患者与0-2错配患者的急性排斥反应发病率有显著性差异,高度致敏患者(移植术前PRA>50%)急性排斥反应发病率较低度致敏患者(PRA 10%～20%)发病率高,移植术后PRA水平持续升高者更容易出现急性排斥反应.结论供、受者之间良好的HLA配型及采用新型免疫抑制药物治疗方案,对预防及减轻致敏患者移植术后急性排斥反应疗效确切.     

Allograft rejection and tubulointerstitial fibrosis in human kidney allografts: Interrogation by urinary cell mRNA profiling

Because the kidney allograft has the potential to function as an in-vivo flow cytometer and facilitate the access of immune cells and kidney parenchymal cells in to the urinary space, we hypothesized that mRNA profiling of urinary cells offers a noninvasive means of assessing the kidney allograft status. We overcame the inherent challenges of urinary cell mRNA profiling by developing pre-amplification protocols to compensate for low RNA yield from urinary cells and by developing robust protocols for absolute quantification mRNAs using RT-PCR assays. Armed with these tools, we undertook first single-center studies urinary cell mRNA profiling and then embarked on the multicenter Clinical Trials in Organ Transplantation-04 study of kidney transplant recipients. We report here our discovery and validation of diagnostic and prognostic biomarkers of acute cellular rejection and of interstitial fibrosis and tubular atrophy (IF/TA). Our urinary cell mRNA profiling studies, in addition to demonstrating the feasibility of accurate diagnosis of acute cellular rejection and IF/TA in the kidney allograft, advance mechanistic and potentially targetable biomarkers. Interventional trials, guided by urinary cell mRNA profiles, may lead to personalized immunosuppression in recipients of kidney allografts.     

FK506与来氟米特预防异种胰岛移植排斥反应的效果

目的　探讨FK5 0 6、来氟米特 (Lef)应用预防大鼠对小鼠异种胰岛移植排斥反应的效果。方法　将 10 0 0～ 12 0 0个大鼠胰岛移植于化学诱导的糖尿病小鼠肾被膜下 ,实验分为对照组、FK 5 0 6组、Lef组和FK5 0 6+Lef组 ,研究胰岛有功能存活情况 ,并在移植后第 5天行病理组织学观察排斥反应。结果　FK5 0 6( 2和 4mg·kg-1·d-1)、Lef( 5、10、2 0mg·kg-1·d-1)术后用药 10d ,胰岛存活时间分别为 ( 8.9± 2 .1)、( 12 .5± 0 .7)、( 10 .8± 1.9)、( 15 .8± 2 .4)、( 18.8± 2 .2 )d ,较对照组( 5 .9± 1.2 )d明显延长 (P <0 .0 1)。FK5 0 6+Lef组移植物存活时间 ( 2 1.8± 1.2 )d ,较单纯用药组效果更好 (P <0 .0 1)。病理组织学显示Lef组与FK5 0 6+Lef组细胞浸润明显减少 ,有更多的完整胰岛存留。结论　FK5 0 6与Lef对异种胰岛移植有抗排斥作用 ,且两药联合应用有协同作用。     

Non-invasive assessment of rejection in pediatric transplant patients: serologic and echocardiographic prediction of biopsy-proven myocardial rejection.

BACKGROUND: Cardiac allograft rejection is a multifocal immune process that is currently assessed using biopsy-guided histologic classification systems (International Society for Heart and Lung Transplantation). Cardiac troponin T and I are established serologic markers of global myocyte damage. The use of load-independent measures of contractility have also been shown to accurately assess the presence of ventricular dysfunction. Little is known about their utility in accurately predicting rejection in the pediatric age group. We undertook the present study to compare rejection grade with echocardiographic and serologic estimates of transplant rejection-related myocardial damage. METHODS: We compared histologic rejection grades (0 to 4) with patient characteristics, echocardiographic measurements, catheterization measurements, and biochemical markers for 86 evaluations in 37 transplant recipients at Children's Hospital. RESULTS: In univariate analyses, biopsy scores correlated (p < 0.05) inversely with left ventricular systolic function (shortening fraction) and contractility (stress velocity index, SVI), and directly with mitral E-wave amplitude. In multivariate analyses, lower contractility and higher mitral E-wave amplitude remained significantly (p < or = 0.01) associated with rejection (SVI, p = 0.002, odds ratio = 0.393; E wave, p = 0.0002, odds ratio = 228). Most rejection episodes were associated with elevation of biochemical markers of myocardial injury. Although troponin I was weakly associated with differences between rejection grades (p = 0.034), troponin T, creatine kinase-MB fraction, and C-reactive protein did not differ with biopsy-rejection scores. Serum markers had a poor predictive capacity for biopsy-detected rejection. Troponin T and I did correlate with increased left ventricular wall thickness and mass. CONCLUSION: Progressively depressed left ventricular contractility and diastolic function are found with worsening pediatric heart transplant rejection-biopsy score; however, sensitive and specific serum markers do not correspond to the degree of active myocardial injury. The use of echocardiographic measures of contractility is associated with a specificity of 91.8% but low sensitivity of 66.7%. Overall we found poor concordance between serum markers and grade of rejection. It is unclear whether myocardial injury as assessed by serum markers, echocardiography, or histologic scoring is more important for assessment of acute rejection or long-term outcome, but it does not appear that serum and tissue markers of rejection can be used interchangeably.     

PTH assays in dialysis patients: Practical considerations

Parathyroid hormone (PTH) 1‐84 is the main biologically active hormone produced by the parathyroid cells. Circulating PTH molecules include the whole PTH 1‐84 along with amino (N) and carboxyl (C) terminal fragments. While PTH is the best available noninvasive biomarker to assess bone turnover in dialysis patients, the biological roles of individual circulating PTH fragments are still not completely known. The understanding that there is an enormous variation in the target specificity of currently available PTH assays for different circulating forms of PTH has led to the evolution of assays from first to second then third generation. With a reduction in kidney function, there is a preferential increase in circulating C fragments and non‐PTH 1‐84 forms, resulting in a decrease in the ratio of PTH 1‐84/non‐PTH 1‐84. However, there are also substantial differences in between‐assay measurements, with several fold variations in results. Targets based on multiples of the upper limit of normal (ULN) should be used rather than PTH ranges using absolute iPTH values. To date, the second‐generation PTH remains the most widely used assay. Current guidelines recommend following iPTH trends rather than absolute values. Herein, we highlight problems and challenges in PTH assays/measurements and their interpretations in dialysis patients.