Defining Treatment and Outcomes of Hepaticojejunostomy Failure Following Pancreaticoduodenectomy

Background

The overall complication rate after pancreaticoduodenectomy (PD) approaches 50 %, with anastomotic failure being the most frequent cause of serious postoperative morbidity. Hepaticojejunostomy leaks (also called bile leaks) are the second most common type of leak, behind pancreaticojejunostomy leaks, yet have been the focus of only a single study as reported by Suzuki et al. (Hepatogastroenterology 50:254–257, 12).

Methods

We reviewed the recent experience with bile leaks at a single, high-volume pancreatic surgery center over a six-year time period.

Results

Bile leaks were identified in 16 out of 715 patients (2.2 %). Low preoperative albumin was associated with an increased risk. Bile leaks typically manifested within the first week after surgery as bilious drainage in a surgically placed drain. Associated warning signs included fever and leukocytosis. Patients with a bile leak frequently developed other complications, including a pancreatic fistula, wound infection, delayed gastric emptying, and sepsis. The impact on perioperative outcomes was comparable to patients with a pancreatic leak. A grading system is proposed based on the International Study Group on Pancreatic Fistula model. Grade A bile leaks were classified as those managed with prolonged drainage by operatively placed drains, grade B bile leaks with percutaneous abdominal drainage, and grade C bile leaks with insertion of a percutaneous transhepatic biliary drainage.

Conclusions

Hepaticojejunostomy leaks are rare after PD. The complication severity ranges from trivial to life threatening and is comparable overall to pancreaticojejunostomy leaks. Surgical intervention is rarely, if ever, required. With prompt and aggressive management, a full recovery can be expected.     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T- lymphocyte lineage

The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.     

Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.     

A canine model of hemophilic (factor VIII:C deficiency) bleeding

A model of bleeding due to clotting factor deficiency has been developed in dogs. Normal and hemophilic (factor VIII:C deficient) animals were used. Bleeding was induced in lightly anesthetized animals by severing the apex of the nail cuticle using a guillotine device. In normal animals, bleeding usually ceased spontaneously after 2-8 min. In contrast, in hemophilic animals, bleeding continued for up to 20 min and necessitated either cauterization or the application of topical thrombin to achieve hemostasis. Pretreatment of the hemophilic animals with canine cryoprecipitate corrected the cuticle bleeding time to within the range noted for normal animals. The method is simple and reproducible and has the advantage that a number of observations can be made sequentially on the same animal. Rebleeding of the cauterized cuticle of the hemophilic animals did not usually occur. This model has considerable potential for the preclinical testing of products considered to bypass or replace factor VIII:C in patients with acquired inhibitors of factor VIII:C and may be adapted to the study of other mechanisms involved in normal and abnormal hemostasis.     

Alpha-II-spectrin after controlled cortical impact in the immature rat brain

Proteolytic processing plays an important role in regulating a wide range of important cellular functions, including processing of cytoskeletal proteins. Loss of cytoskeletal proteins such as spectrin is an important characteristic in a variety of acute central nervous system injuries including ischemia, spinal cord injury and traumatic brain injury (TBI). The literature contains extensive information on the proteolytic degradation of alpha-II-spectrin after TBI in the adult brain. By contrast, there is limited knowledge on the characteristics and relevance of these important processes in the immature brain. The present experiments examine TBI-induced proteolytic processing of alpha-II-spectrin after TBI in the immature rat brain. Distinct proteolytic products resulting from the degradation of the cytoskeletal protein alpha-II-spectrin by calpain and caspase 3 were readily detectable in cortical brain parenchyma and cerebrospinal fluid after TBI in immature rats.     

Protophormia terraenovae. A new allergenic species in amateur fishermen of Caceres,Spain

BackgroundAsticot maggot (Blowfly, Calliphoridae family) is the most important live bait used for angling in our country. Prevalence of allergy to live fish bait in occupationally exposed workers has been described. The purpose of this study was to determine the prevalence of asticot allergy in amateur fishermen and the identification of marketed asticot species in Cáceres, Spain.Materials and MethodsSeventy-two randomised selected patients (Angler's Society of Cáceres) completed a questionnaire about fishing habits and allergic symptoms related with live bait handling. Skin prick test (SPT) with local asticot and common earthworm extracts were performed. Serum IgE levels to imported species (Protophormia terraenovae, Calliphora vomitoria, Lucilia sericata, Lumbricus terrestris) were measured. Local asticot and common earthworm samples were obtained for taxonomic identification. Data were analysed using the SPSS 12.0 software.ResultsFive patients (7 %) reported allergic symptoms caused by asticot maggots. All of them were positive for SPT to asticot and specific IgE to P. terraenovae. Sensitisation to P. terraenovae was found in 40 patients (58.8 %). No associated factors for asticot allergy were observed. Larvae and adult flies of local asticot samples were identified as P. terraenovae.ConclusionsCommercially available asticot, in Cáceres, is composed by P. terraenovae larvae (Diptera. Calliphoridae). A 7 % prevalence of P. terraenovae allergy in amateur fishermen of Cáceres was obtained. The allergenic potential of P. terraenovae seems to be greater than that of other blowflies and L. terrestris. The SPT with P. terraenovae extract is a very sensitive and specific technique in the diagnosis of live bait allergy in fishermen.     

Miglustat in patients with Niemann-Pick disease Type C (NP-C): A multicenter observational retrospective cohort study

Miglustat has been shown to stabilize disease progression in children, juveniles and adults with Niemann-Pick disease type C (NP-C), a rare genetic disorder characterized by progressive neurological deterioration. We report findings from a retrospective observational cohort study assessing the effects of miglustat on neurological disease progression in patients treated in the clinical practice setting. Data from all NP-C patients prescribed miglustat at 25 expert centers were evaluated using a disease disability scale. The scale analyzed four key parameters of neurological disease progression in NP-C (ambulation, manipulation, language, swallowing). Mean individual parameter scores and a composite score were calculated at baseline (time of diagnosis) and up to 4 follow-up visits. Overall, 66 patients were included (mean [SD] age at diagnosis, 9.7 [7.6] years, and at treatment start, 12.8 [9.5] years). The median (range) miglustat exposure was 1.46 (0.05–4.51) years. Mean annual progression was +0.11 score units/year from diagnosis to treatment start, indicating disease progression prior to therapy, and decreasing to −0.01 score units/year from treatment start to last clinic visit, indicating stabilization. Stabilization of neurological disease on miglustat was observed in all age groups, but the magnitude of the effect was greater in patients diagnosed in late childhood and in juveniles and adults. Stabilization of neurological disease was also observed in a subset of 19 patients with extended pre-treatment information. Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C.