Intestinal Transplantation Fishbein, Thomas M
The New England journal of medicine,
09/2009, Volume:
361, Issue:
10
Journal Article
Peer reviewed
Intestinal transplantation has become an option for selected patients with irreversible gut failure. Candidates include patients with complications of parenteral nutrition, those with unresectable ...mesenteric tumors, and those who cannot adapt to the limitations of intestinal failure. This review summarizes recent experience, including the management challenges of immunosuppression and organ rejection.
Intestinal transplantation has become an option for selected patients with irreversible gut failure. This review summarizes recent experience, including the management challenges of immunosuppression and organ rejection.
The results of intestinal transplantation have improved over the past decade. During this period, the number of intestinal transplant procedures performed in North America has increased by a factor of three.
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In 2008, a total of 185 intestinal transplantations were performed in the United States, and 221 patients were registered on the waiting list as of June 2009 (http://optn.transplant.hrsa.gov). Early attempts at transplantation were hindered by technical and immunologic complications that led to graft failure or death. As a result of recent surgical advances, control of acute cellular rejection, and a decrease in lethal infections, the rate of patient survival . . .
Abstract
Human noroviruses are a major cause of diarrheal illness, but pathogenesis is poorly understood. Here, we investigate the cellular tropism of norovirus in specimens from four ...immunocompromised patients. Abundant norovirus antigen and RNA are detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. Negative-sense viral RNA, a marker of active viral replication, is found predominantly in intestinal epithelial cells, with chromogranin A-positive enteroendocrine cells (EECs) identified as a permissive cell type in this patient. These findings are consistent with the detection of norovirus-positive EECs in the other three immunocompromised patients. Investigation of the signaling pathways induced in EECs that mediate communication between the gut and brain may clarify mechanisms of pathogenesis and lead to the development of in vitro model systems in which to evaluate norovirus vaccines and treatment.
There is a paucity of data on long‐term outcomes following visceral transplantation in the contemporary era. This is a single‐center retrospective analysis of all visceral allograft recipients who ...underwent transplant between November 2003 and December 2013 with at least 3‐year follow‐up data. Clinical data from a prospectively maintained database were used to assess outcomes including patient and graft survival. Of 174 recipients, 90 were adults and 84 were pediatric patients. Types of visceral transplants were isolated intestinal transplant (56.3%), combined liver‐intestinal transplant (25.3%), multivisceral transplant (16.1%), and modified multivisceral transplant (2.3%). Three‐, 5‐, and 10‐year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3‐, 5‐, and 10‐year overall graft survival was 67%, 62%, and 61%, respectively. In multivariable analysis, significant predictors of survival included pediatric recipient (P = .001), donor/recipient weight ratio <0.9 (P = .008), no episodes of severe acute rejection (P = .021), cold ischemia time <8 hours (P = .014), and shorter hospital stay (P = .0001). In conclusion, visceral transplantation remains a good option for treatment of end‐stage intestinal failure with parenteral nutritional complications. Proper graft selection, shorter cold ischemia time, and improvement of immunosuppression regimens could significantly improve the long‐term survival.
While visceral transplantation has better long‐term outcomes in the new era, survival could improve significantly with proper graft selection, shorter cold ischemia time, and improved immunosuppression regimens.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adult Intestinal Transplantation Matsumoto, Cal S; Subramanian, Sukanya; Fishbein, Thomas M
Gastroenterology clinics of North America,
06/2018, Volume:
47, Issue:
2
Journal Article
Peer reviewed
Open access
Adult intestinal transplantation differs significantly from pediatric intestinal transplantation. While indications have remained largely consistent since 2000, indications for adults have expanded ...over the last two decades to include motility disorders and desmoid tumors. Graft type in adult recipients depends on the distinct anatomic characteristics of the adult recipient. Colonic inclusion, while initially speculated to portend unfavorable outcomes due to complex host-bacterial interactions has increased over the past two decades with superior graft survival and improved patient quality of life. Overall, outcomes have steadily improved. For adult intestinal transplant candidates, intestinal transplantation remains a mainstay therapy for complicated intestinal failure and is a promising option for other life threatening and debilitating conditions.
Postoperative computed tomography imaging has been shown to play an important role in avoiding failure-to-rescue. We sought to examine the impact of the timing of such imaging studies on outcomes ...after pancreatectomy.
Patients who underwent pancreatic resection at our institution from 2017 to 2022 were reviewed retrospectively to identify those undergoing computed tomography for any indication before discharge. Patients were subdivided by the postoperative day that the first computed tomography scan was obtained: immediate (postoperative day <3), early (postoperative day 3–7), and delayed (postoperative day >7).
Of 370 patients, 110 (30%) had a computed tomography during the initial surgical stay. The 3 timing groups were similar in age, comorbidities, pathology, operative time, and number of scans. When comparing the early with the delayed group, we found that antibiotic usage, percutaneous drainage, and overall invasive interventions during surgical stay were all similar. However, those patients who were scanned in the early period had significantly shorter length of stay (17.05 vs 22.82, P = .0008) and fewer composite days hospitalized (20.1 vs 24.9, P = .01) relative to the delayed group. Importantly, early computed tomography imaging was found to be the only independent predictor of a postoperative length of stay ≤15 days on multivariate analysis. Surgical stay mortality rates were significantly lower in the early compared with delayed group (0% vs 11%, P = .02). A change in treatment was observed in 59% after computed tomography, with 15% undergoing invasive interventions, 27% treated medically, and 16% with expectant management.
In our cohort, patients imaged early after pancreatectomy experienced shorter hospital stays and lower inpatient mortality relative to those scanned after the first postoperative week.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatocellular carcinoma (HCC) represents a typical inflammation-associated cancer. Tissue resident innate lymphoid cells (ILCs) have been suggested to control tumour surveillance. Here, we studied ...how the local cytokine milieu controls ILCs in HCC.
We performed bulk RNA sequencing of HCC tissue as well as flow cytometry and single-cell RNA sequencing of enriched ILCs from non-tumour liver, margin and tumour core derived from 48 patients with HCC. Simultaneous measurement of protein and RNA expression at the single-cell level (AbSeq) identified precise signatures of ILC subgroups. In vitro culturing of ILCs was used to validate findings from in silico analysis. Analysis of RNA-sequencing data from large HCC cohorts allowed stratification and survival analysis based on transcriptomic signatures.
RNA sequencing of tumour, non-tumour and margin identified tumour-dependent gradients, which were associated with poor survival and control of ILC plasticity. Single-cell RNA sequencing and flow cytometry of ILCs from HCC livers identified natural killer (NK)-like cells in the non-tumour tissue, losing their cytotoxic profile as they transitioned into tumour ILC1 and NK-like-ILC3 cells. Tumour ILC composition was mediated by cytokine gradients that directed ILC plasticity towards activated tumour ILC2s. This was liver-specific and not seen in ILCs from peripheral blood mononuclear cells. Patients with high ILC2/ILC1 ratio expressed interleukin-33 in the tumour that promoted ILC2 generation, which was associated with better survival.
Our results suggest that the tumour cytokine milieu controls ILC composition and HCC outcome. Specific changes of cytokines modify ILC composition in the tumour by inducing plasticity and alter ILC function.
Disparities in hepatocellular carcinoma (HCC) incidence and survival have been observed between ethnic groups including African-Americans (AA) and European-Americans (EA). The evaluation of the ...changes in the levels of metabolites in samples stratified by race could provide a snapshot of ethnically diverse disease related pathways and identify reliable biomarkers. In this study, we considered AA and EA to investigate metabolites that may be associated with HCC in a race-specific manner. The levels of 46 metabolites in plasma samples, collected from patients recruited at MedStar Georgetown University Hospital, were analyzed by Agilent GC-qMS in selected ion monitoring (SIM) mode. A least absolute shrinkage and selection operator (LASSO) regression model was applied to select metabolites with significant changes in HCC vs. cirrhosis in three groups: (1) AA and EA combined; (2) AA separately; and (3) EA separately. In addition, metabolites that distinguish HCC cases from cirrhosis in these three groups were selected by excluding those without HCV infection. The performances of the metabolites selected by LASSO in each group were evaluated through a leave-one-out cross-validation. We identified race-specific metabolites that differentiated HCC cases from cirrhotic controls, yielding better area under the receiver operating characteristics (ROC) curve (AUC) compared to alpha-fetoprotein (AFP), the serological marker widely used for the diagnosis of HCC. This study sheds light on metabolites that could potentially be used as biomarkers for HCC by monitoring their levels in high-risk population of cirrhotic patients in a race-specific manner.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alpha-synuclein (αS) is a nerve cell protein associated with Parkinson disease (PD). Accumulation of αS within the enteric nervous system (ENS) and its traffic from the gut to the brain are ...implicated in the pathogenesis and progression of PD. αS has no known function in humans and the reason for its accumulation within the ENS is unknown. Several recent studies conducted in rodents have linked αS to immune cell activation in the central nervous system. We hypothesized that αS in the ENS might play a role in the innate immune defenses of the human gastrointestinal (GI) tract.
We immunostained endoscopic biopsies for αS from children with documented gastric and duodenal inflammation and intestinal allograft recipients who contracted norovirus. To determine whether αS exhibited immune-modulatory activity, we examined whether human αS induced leukocyte migration and dendritic cell maturation.
We showed that the expression of αS in the enteric neurites of the upper GI tract of pediatric patients positively correlated with the degree of acute and chronic inflammation in the intestinal wall. In intestinal allograft subjects who were closely monitored for infection, expression of αS was induced during norovirus infection. We also demonstrated that both monomeric and oligomeric αS have potent chemoattractant activity, causing the migration of neutrophils and monocytes dependent on the presence of the integrin subunit, CD11b, and that both forms of αS stimulate dendritic cell maturation.
These findings strongly suggest that αS is expressed within the human ENS to direct intestinal inflammation and implicates common GI infections in the pathogenesis of PD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In the recent PORSCH trial, a three-part postpancreatectomy care algorithm was employed with a near 50 % reduction in mortality. We hypothesized that clinical care congruent with this protocol would ...correlate with better outcomes in our patients.
Real-world postoperative care was compared to the pathway described by the PORSCH trial and patients were assigned into groups based on congruence with its recommendations. The primary composite outcome (PCO) consisted of 90-day mortality, organ failure, and interventions for bleeding.
Of 289 patients, care of 12 % was entirely congruent with the PORSCH algorithm. The PCO was recorded in 9 % of the PORSCH care group, 8 % of the Partial-PORSCH care group, and 19 % of the Non-PORSCH care group (p = 0.044). Adverse outcomes were highest when pancreaticoduodenectomy patients received care incongruent with the algorithm's CT imaging recommendations.
These results add external validity to the principles of clinical care underlying the PORSCH algorithm.
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•Derangements in labwork and vital signs after pancreatectomy warrant investigation.•Early detection and treatment of postpancreatectomy complications improves outcomes.•The PORSCH trial's algorithm may reduce morbidity and mortality in clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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