The surgical risk of pancreas transplantation in the cyclosporine era: an overview

BACKGROUND: Pancreas transplants are still associated with the highest surgical complication rate of all routinely performed solid organ transplants. To date, the impact of serious surgical complications in the cyclosporine era on perioperative patient morbidity, graft and patient survival, and hospital costs has not been analyzed in detail. STUDY DESIGN: We retrospectively studied surgical complications after 445 consecutive pancreas transplants (45% simultaneous pancreas-kidney [SPK], 24% pancreas after kidney [PAK], and 31% pancreas transplant alone [PTA]). Of these, 80% were primary transplants, 20% were retransplants. Cadaver donors were used in 92%, living related donors in 8%. To develop guidelines for their prevention and management, we studied the impact of significant surgical complications (intra-abdominal infections, vascular graft thrombosis, and anastomotic leak) requiring relaparotomy on graft and patient survival. RESULTS: Relaparotomy was required after 32% of all pancreas transplants (SPK: 36%, PAK: 25%, PTA: 16% [p = 0.04]). Perioperative mortality was 9%. Graft and patient survival rates were significantly lower for recipients with (versus without) relaparotomy. The most common procedures were drainage of intra-abdominal abscess with graft necrosectomy (50% of all relaparotomies) and transplant pancreatectomy (34%). The most common causes of relaparotomy were intra-abdominal infection, vascular graft thrombosis, and anastomotic leak. Intra-abdominal infection occurred in 20% (SPK: 18%, PAK: 24%, PTA: 20% [p = NS]). The rate was significantly higher for living related donor (42%) versus cadaver donor (18%) recipients and for those with enteric-drained (39%) versus bladder-drained (18%) transplants. Graft and patient survival rates were significantly lower for recipients with (versus without) intra-abdominal infection. Outcome was better after bacterial (versus fungal) infections. For SPK recipients, those not on dialysis before the transplant had significantly higher graft survival than those on dialysis. Vascular graft thrombosis occurred in 12% of all recipients. The rate was significantly higher for PAK (21%) than for PTA (10%) and SPK (9%) recipients. It was significantly lower for recipients of grafts with donor iliac Y-graft reconstruction (versus all other types of arterial reconstruction) and with right-sided (versus left-sided) graft placement. Of note, patient survival was not different for recipients with versus without vascular graft thrombosis. The incidence of anastomotic or duodenal stump leaks was 10%; of these recipients, 70% required relaparotomy. Patient and graft survival rates were no different for recipients with versus without leaks. CONCLUSIONS: Serious surgical complications occurred in 35% of pancreas recipients and had a significant impact on patient and graft survival. Based on multivariate risk factor analyses, we recommend the following: donors over 45 years and those dying of cerebrocardiovascular disease should not be used; recipients over 45 years and those with a history of cardiac disease should be considered for a kidney transplant alone (KTA); surgical technique for graft procurement, preparation, and implantation should be meticulous; right-sided implantation and arterial Y-graft reconstruction should be performed when possible, since they had the highest success rates; when complications require relaparotomy, the focus must switch from graft salvage to life preservation; and the threshold for pancreatectomy should be low. Diagnosis should be timely, and treatment and relaparotomy expeditious. These cornerstones of success should help decrease the risk of surgical complications and mortality after pancreas transplants.     

Revascularization of internal iliac arteries during aortoiliac surgery: a multicenter study

Prenatal screening for fetal abnormalities in an accepted part of modern obstetric management. Improvements on current screening procedures need to address increased diagnostic efficacy and earlier diagnosis. This study evaluates diagnostic efficacy of PAPP-A and F beta-hCG in the detection of first trimester pregnancy abnormalities, including Down syndrome (DS). Of 731 pregnant volunteers, obtained from a mature age population undergoing chorionic villus sampling (CVS), 17 DS and 11 compromised (six numerical (excluding sex chromosome) aneuploidies, five spontaneously failed) pregnancies were detected. Application of an algorithm, which combines PAPP-A and F beta-hCG levels with material age, detected 66.6 per cent of DS pregnancies for a five per cent false positive rate. Similarly, for a 1-2 per cent recall rate, 72.2 per cent of compromised pregnancies were detected. This report supports the notion that prenatal screening at 9-12 weeks of pregnancy is achievable with PAPP-A and F beta hCG quantitation. Whereas mid-gestational screening targetted the detection of fetal abnormalities, screening earlier in pregnancy will detect other pregnancy-related abnormalities, in addition to aneuploidy.     

Use of balloon-expandable metallic stents in the management of bronchial stenosis and bronchomalacia after lung transplantation

STUDY OBJECTIVES: Bronchial stenosis (BS) and bronchomalacia (BM) are often associated with lung allograft rejection or infection in lung transplant (LT) recipients. We reviewed our experience using balloon-expandable metallic (Palmaz) stents in the management of BS and BM in LT. DESIGN: Retrospective review of cases. PATIENTS: LT recipients with bronchoscopic and spirometric evidence of BS and BM. INTERVENTIONS: Serial balloon dilation was performed for BS. Stent placement was done for refractory or recurrent BS, or persistent focal BM. RESULTS: Twelve of 129 LT bronchial anastomoses at risk (9.3%) had complications, which included 11 BS and 5 BM. Four BS were accompanied by BM either concurrently or subsequently. The only isolated BM was associated with acute rejection and resolved after appropriate medical therapy. Balloon dilations alone were successful in relieving BS in three cases. Seven patients received a total of 11 stents. Stents were placed under conscious sedation using a flexible bronchoscope. Five of the seven patients had spirometric improvements after stent placements. One patient had no spirometric improvement, and another died before a follow-up study was done. There were no complications during stent placements. However, complications after stent placements included partial dehiscence of the stent from the bronchial wall, stent migration, partial obstruction of a segmental bronchial orifice by a stent in the main bronchus, and longitudinal stent collapse. One stent was successfully removed using a flexible bronchoscope in the endoscopy suite, and two others were removed by rigid bronchoscopy in the operating room. CONCLUSIONS: Endobronchial placement of the Palmaz stent in LT recipients is relatively easy, and it can be removed if needed. However, because there are significant potential complications, the future use of this stent as an airway prosthesis in LT remains unclear.     

Trovafloxacin: an overview

Trovafloxacin, a new synthetic naphthyridine fluoroquinolone antibiotic, is a broad-spectrum agent available orally and intravenously. It was recently approved by the Food and Drug Administration for the treatment of selected pulmonary, surgical, intraabdominal, gynecologic, pelvic, skin, and urinary tract infections. Its spectrum of activity includes aerobic gram-positive and gram-negative organisms as well as anaerobic pathogens. It is rapidly absorbed after oral administration, achieves good tissue and cerebrospinal fluid penetration, and has a half-life that allows once-daily dosing. It is hepatically metabolized, and dosage adjustments are necessary for patients with severe hepatic dysfunction but not for those with mild or moderate dysfunction or renal dysfunction. The drug has a favorable safety profile, and a high tendency for transient first-dose dizziness and/or lightheadedness in young women. Similar to other quinolones, trovafloxacin should not be taken with antacids that contain aluminum or magnesium, sucralfate, or ferrous sulfate. Trovafloxacin may prove beneficial as it allows for oral or intravenous monotherapy against indicated infections that normally require multidrug, broad-spectrum antibiotic coverage.     

Hiccup in adults: an overview

Hiccup is a forceful, involuntary inspiration commonly experienced by fetuses, children and adults. Its purpose is unknown and its pathophysiology still poorly understood. Short hiccup bouts are mostly associated with gastric distention or alcohol intake, resolve spontaneously or with simple folk remedies and do not require medical attention. In contrast, prolonged hiccup is a rare but disabling condition which can induce depression, weight loss and sleep deprivation. A wide variety of pathological conditions can cause chronic hiccup: myocardial infarction, brain tumour, renal failure, prostate cancer, abdominal surgery etc. Detailed medical history and physical examinations will often guide diagnostic investigations (abdominal ultrasound, chest or brain CT scan...). Gastric and duodenal ulcers, gastritis, oesophageal reflux and oesophagitis are commonly observed in chronic hiccup patients and upper gastrointestinal investigations (endoscopy, pH monitoring and manometry) should be included in the diagnostic evaluation systematically. Etiological treatment is not always available and chronic hiccup treatment has classically relied on metoclopramide and chlorpromazine. Recently, baclofen (LIORESAL) has emerged as a safe and often effective treatment.     

The cerebellum: an overview

Life has been compared to a beautiful tapestry, woven in intricate design of many threads and colors. By means of physics, chemistry, physiology, anatomy, embryology and genetics we unravel this texture, separate its constituent threads and colors, but lose the pattern as a whole. These analytical sciences have enormously increased our knowledge of life's constituent elements and processes, but the pattern of the tapestry is usually neglected or ignored.     

Transcription factors: an overview

In this article, we report complementation of the genetic defect of isolated Gunn rat hepatocytes by a highly efficient method for lipofection. Transfections were performed 24 h after plating by using the cationic liposome DOTAP. On average, transfection efficiencies of 21% lacZ+ cells with Wag/Rij rat cells and 27% lacZ+ cells with Gunn rat cells could be obtained when the parenchymal cells were transfected in a hormone-defined, serum-free medium. LacZ expression vectors with the CMV promoter were more effective than constructs containing the RSV or the TK promoter. A linear relationship between the viability of hepatocytes after isolation and the percentage of lacZ+ cells was observed with both rat strains, with a maximum of 40% lacZ+ cells at a viability of 94%. The transfection efficiencies were significantly lower in the absence of growth factors, in dexamethasone-containing medium, or when serum was present during plating. Our data are consistent with the assumption that a mitotic event is required for efficient lipofection. Bilirubin conjugation activity could be detected in microsomes from Gunn rat hepatocytes after transfection with two different B-UDPGT expression constructs. Highest conjugation activity was achieved with a vector containing a terminal intron. With this construct on average 4% of the bilirubin conjugation activity of normal human liver microsomes could be achieved in total microsomes of transfected Gunn rat hepatocytes. The implications of our data for gene therapy of hepatic disease with nonviral vectors, in particular bilirubin conjugation deficiency (Crigler-Najjar disease) are discussed.     

Apoptosis detection: an overview

As with women in general, the vicissitudes of the female physician who suffers from a substance use disorder have been understudied, and such persons remain underrepresented in treatment. The purpose of the present study is to describe the similarities and differences between female and male physicians presenting for assessment; 108 physicians in total were included in the study, 10 of whom were female. Demographically, we found that the female physicians were more likely to be single and younger than their male counterparts. On clinical indices, females showed less impairment on legal and medical functioning, and better capability in sustaining abstinence and eliminating environmental cues to relapse. Of the women with substance use disorders, higher rates of comorbidity were found than with males. Although there were no significant differences in overall severity, males were more likely to be recommended to more intensive levels of care for either substance use or psychiatric disorders. The female physicians were recommended to a level of care of a lower intensity, but more often to a treatment with a dual-diagnosis focus. These findings are discussed in terms of the vulnerabilities of the female physician, barriers to treatment, tailoring treatment to female needs, and opportunities for prevention and further research.     

The pathology of the pulmonary arteries in lung tumors

A study was undertaken to analyse the type and extent of pathological changes in the pulmonary arteries in non-small cell malignant tumours of the lung. Large-section histological preparations were made from 33 squamous cell carcinomas and 30 adenocarcinomas (T1 and T2 tumours) and classified according to tumour margin area (zone 1), intermediate area (zone 2) and tumour centre (zone 3). Transmural tumour growth with intraluminal cell formations in the pulmonary artery branches were found in the centre of all adenocarcinomas and 86% of squamous cell carcinomas, involving subsegment, prelobular and lobular arteries. Obstructive and obliterative changes in the pulmonary arteries as the result of tumour compression and secondary fibrosing changes predominantly occurred in the centre of all tumours. They were less common and less marked in zones 1 and 2. -Pulmonary artery branches in lung tumours of stages T1 and T2 showed marked infiltrating, obliterative and secondary inflammatory changes as far as complete vascular occlusions. These observations indicate that cytotoxic drugs, introduced via the systemic circulation, cannot reach and therefore not exert their effects in extensive areas of tumour.     

Genetic factors in lung disease: atopy and bronchial asthma

Human CD38 is a surface molecule which has been attributed the function of a signaling channel leading to cellular activation and proliferation, an ectoenzyme with multiple function as well as an inducer of Ca2+ mobilization from cytoplasmic stores. The effect mediated by CD38 have been studied in different cell populations: the results obtained in human B cells are apparently contradictory, with CD38 simultaneously leading to apoptosis in early B cells while increasing survival in cells derived from lymph node germinal center. Other effects recently reported concern a different potential in terms of signaling in early B cells and derived cell lines or in more detailed disease models of human leukemia, namely B chronic lymphocytic leukemia cells. To complete the picture of the effects mediated by CD38 in the B cell compartment, we have studied the signals elicited by ligation of the human molecule in mature B cells from circulating pool and also from spleen of normal individuals. The information obtained completes the picture of CD38 and mature B cells, where we also studied the contribution of relevant cytokines involved in maintenance and differentiation of these normal cells, namely IL-1 alpha, IL-2, IL-4 and IL-6. Our results indicate that human CD38 plays a key role as a co-receptor in mature B cells from normal individuals.     

Monoamine oxidase in schizophrenia: an overview

A brief history and summary of studies designed to elucidate the role of monoamine oxidase (MAO) in schizophrenia are presented. The majority of these studies have reported a decrease in the platelet enzyme activity of chronic schizophrenic patients when compared to controls. Difficulties encountered when comparing MAO activity measured in different patient populations are also considered. Finally, the significance of decreased platelet MAO activity is discussed with respect to its possible etiological role in some forms of schizophrenia.     

Neurotrophic factors in the treatment of neurotoxicity: an overview

In recent years, major advances have been made in our understanding of neurotrophic factors and the role they play in the development and maintenance of the nervous system. This knowledge, combined with major advances in molecular biology, have enabled investigators to begin considering their applications to clinical problems. The toxic neuropathies may prove to be one of the simplest and most practical clinical settings for the early use of neurotrophic factors. In this brief review, we provide an overview of some of the most important neurotrophic factors, and summarize the major preclinical studies which suggest that they may be useful in the treatment of toxic neuropathy.