Preneoplastic Lesion in a Pancreas Allograft: Dilemma for the Pancreas Transplant Surgeon.

Although the relationship between immunosuppression and cancer risk is well-documented, the association between immunosuppression and the development of preneoplastic lesions (PNL) is less clear. PNLs pose a unique clinical conundrum in the transplanted pancreas because their prevalence in the general population is not infrequent. We present the case of a 58-year-old man with a history of diabetes mellitus type 1 who underwent successful pancreas transplantation with bladder drainage. His kidney function failed 13 years after his transplant and he developed recurrent painful hematuria with symptomatic anemia 2 years after initiating hemodialysis. Upon work-up, he was found to have a 4 cm intraductal papillary mucinous neoplasm in his pancreas allograft. At his enteric conversion, the intraductal papillary mucinous neoplasm was removed through a distal pancreatectomy due to concern for its malignant potential. He recovered well from surgery and continues to be insulin-free. With the rising incidence of PNLs from improved detection and the improved survival of pancreas allografts, the implications of PNLs may be more pronounced in the future. This case raises several important considerations for the pancreas transplant surgeon regarding adequate allograft surveillance protocols, treatment, and follow-up.

Long-term Graft Survival After Kidney Allograft Torsion: Rapid Diagnosis and Surgical Management Key to Reversibility of Injury.

INTRODUCTION: Kidney allograft torsion (KAT) is a rare complication of kidney transplantation (KT) that occurs when the transplanted kidney rotates around its vascular pedicle, which may result in a catastrophic compromise of the graft's blood supply, deterioration of kidney function, and eventually premature graft death. CASE REPORT: We report the case of a patient who had an acute kidney injury (AKI) episode from KAT. Her diagnosis was ascertained expeditiously and she had prompt surgical management. Five years after the KAT event, her baseline creatinine (Cr) stabilized around 1.6 mg/dL and she has achieved >8-year graft survival. DISCUSSION: This case illustrates the reversibility of injury that can occur after a KAT event with a commensurate return to baseline kidney function when KAT is promptly diagnosed and treated. A high index of suspicion of this uncommon but catastrophic complication of KT must be maintained to achieve desirable long-term outcomes. A diagnosis of KAT must be considered when routine etiologies of an acute deterioration of kidney allograft function have been excluded. Finally, prophylactic nephropexy must be strongly considered with intraperitoneal placement of a kidney allograft to avoid KAT.

Sinistral Portal Hypertension After Live Segmental Pancreas Donation: A Long-Term Sequelae Presenting With Life-Threatening Upper Gastrointestinal Hemorrhage.

INTRODUCTION: Variceal hemorrhage from sinistral portal hypertension has never been reported as a complication of live pancreas donation. CASE REPORT: We present a 68-year-old patient who underwent a simultaneous live-donor laparoscopic segmental pancreatectomy and nephrectomy for the purposes of donating to her daughter. Her postoperative course was significant for an episode of acute pancreatitis with a pseudocyst formation. More than a decade later, she presented with variceal hemorrhage from sinistral portal hypertension, which after a diagnostic work-up, prompted a laparoscopic splenectomy. DISCUSSION: Sinistral portal hypertension is a long-term complication of live-donor pancreas donation.

Defining the Tipping Point in Surgical Performance for Laparoscopic Donor Nephrectomy Among Transplant Surgery Fellows: A Risk-Adjusted Cumulative Summation Learning Curve Analysis.

The United Network for Organ Sharing recommends that fellowship-trained surgeons participate in 15 laparoscopic donor nephrectomy (LDN) procedures to be considered proficient. The American Society of Transplant Surgeons (ASTS) mandates 12 LDNs during an abdominal transplant surgery fellowship. We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve of novice transplant surgery fellows (TSFs). Between January 2000 and December 2014, 30 novice TSFs participated in the organ procurement rotation of our ASTS-approved abdominal transplant surgery fellowship. Measures of surgical performance included intraoperative time, estimated blood loss, and incidence of intraoperative complications. The performance of senior TSFs was used to benchmark novice TSF performance. Scores were tabulated in a learning curve model, adjusting for case complexity and prior TSF case volume. Rates of adverse surgical events were significantly higher for novice TSFs than for senior TSFs. In univariable analysis, multiple renal arteries, high BMI, prior abdominal surgery, male donor, and nephrolithiasis were correlated with higher incidence of adverse surgical events. Based on the RACUSUM model, high intraoperative time is mitigated after 28 procedures, incidence of intraoperative complications tends to diminish after 24 procedures, and improvement in estimated blood loss did not remain consistent. TSFs exhibit a tipping point in LDN performance by 24-28 cases and proficiency by 35-38 cases.

Intrapancreatic Splenule in a Pancreas Allograft: Case Report.

A 16-year-old white man was involved in a motor vehicle collision and suffered head, chest, and abdominal trauma. Despite initial resuscitative efforts, he progressed to brain death and was designated to be an organ donor by his family. He had no earlier medical or surgical history and no high-risk behaviors. Blood work revealed normal creatinine, liver function tests, lipase, and amylase. Viral serologies were negative except for cytomegalovirus IgG and Epstein-Barr virus nucleic acid. Imaging revealed a right kidney contusion, a manubrial fracture, and fractures of right first rib and bilateral scapulae. No other abdominal trauma was identified, specifically to the pancreas, duodenum, or spleen. Our transplant center accepted the pancreas from this donor. During back-table inspection of the pancreas, a 1.5 × 1.5 cm dark purple rubbery mass was identified within the parenchyma of the pancreas in the tail. An incisional biopsy of the lesion was sent for frozen section, which yielded a mixed inflammatory infiltrate consisting of neutrophils and lymphocytes and an overlying fibrous capsule. The diagnosis of lymphoma or another neoplasm could not be definitely ruled out. Owing to uncertainty in diagnosis, the entire lesion was excised along with the distal pancreas with the use of a linear stapler. The staple line was oversewn with running 4-0 polypropylene suture, and the pancreas was transplanted. After surgery, the pancreas allograft functioned well with a small pancreatic leak, which had resolved by the first postoperative outpatient visit.

Mutational analysis of the repeated open reading frames, ORFs 63 and 70 and ORFs 64 and 69, of varicella-zoster virus.

Varicella-zoster virus (VZV) open reading frame 63 (ORF63), located between nucleotides 110581 and 111417 in the internal repeat region, encodes a nuclear phosphoprotein which is homologous to herpes simplex virus type 1 (HSV-1) ICP22 and is duplicated in the terminal repeat region as ORF70 (nucleotides 118480 to 119316). We evaluated the role of ORFs 63 and 70 in VZV replication, using recombinant VZV cosmids and PCR-based mutagenesis to make single and dual deletions of these ORFs. VZV was recovered within 8 to 10 days when cosmids with single deletions were transfected into melanoma cells along with the three intact VZV cosmids. In contrast, VZV was not detected in transfections carried out with a dual deletion cosmid. Infectious virus was recovered when ORF63 was cloned into a nonnative AvrII site in this cosmid, confirming that failure to generate virus was due to the dual ORF63/70 deletion and that replication required at least one gene copy. This requirement may be related to our observation that ORF63 interacts directly with ORF62, the major immediate-early transactivating protein of VZV. ORF64 is located within the inverted repeat region between nucleotides 111565 and 112107; it has some homology to the HSV-1 Us10 gene and is duplicated as ORF69 (nucleotides 117790 to 118332). ORF64 and ORF69 were deleted individually or simultaneously using the VZV cosmid system. Single deletions of ORF64 or ORF69 yielded viral plaques with the same kinetics and morphology as viruses generated with the parental cosmids. The dual deletion of ORF64 and ORF69 was associated with an abnormal plaque phenotype characterized by very large, multinucleated syncytia. Finally, all of the deletion mutants that yielded recombinants retained infectivity for human T cells in vitro and replicated efficiently in human skin in the SCIDhu mouse model of VZV pathogenesis.

Intracellular pH in isolated rat renal papillary thin limbs of Henle's loop.

Intracellular pH (pHi) was measured in isolated, nonperfused and perfused rat papillary thin limbs of Henle's loops in N-2-hydroxyethylpiperazine-N'-2-ethansulfonic acid (HEPES)- or HEPES/bicarbonate-buffered medium at pH 7.4 using the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF). Resting pHi was about 6.7 in descending thin limbs (DTL) and about 6.9 in ascending thin limbs (ATL), even with a medium pH of 7.4. These values appeared to reflect the acid pH of the blood in the neighboring vasa recta found in vivo. The resting pHi did not differ whether or not the medium contained bicarbonate although the total buffering capacity of the tubule cells was increased in the presence of bicarbonate. In nonperfused DTL and ATL, pHi was further acidified following an NH4Cl pulse. The rate of recovery of pHi from this level to the resting pHi was reduced by Na+ removal from the bath in both DTL and ATL and by the addition of ethylisopropylamiloride (EIPA) to the bath in the presence of Na+ in DTL. The rate of recovery was not affected by Cl- removal from the bath or K+ (75 mM) or 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) addition to the bath in either DTL or ATL. These results suggest that the common, amiloride-sensitive, basolateral Na+/H+ exchanger plays a role in the regulation of pHi in rat papillary DTL but that a different basolateral Na+/H+ exchanger or a luminal Na+/H+ exchanger is important in rat papillary ATL.

Basolateral regulation of pHi in isolated snake renal proximal tubules in presence and absence of bicarbonate.

Intracellular pH (pHi) and its basolateral regulation were studied in isolated proximal-proximal and distal-proximal segments of garter snake (Thamnophis spp.) renal tubules with oil-filled lumens in HEPES-buffered and in HEPES-HCO-3-buffered media (pH 7.4 at 25 degrees C). pHi was measured with the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) under resting conditions and in response to NH4Cl pulse. Resting pHi (approximately 7.1-7.2) and its response to and rate of recovery (dpHi/dt) from an NH4Cl pulse were not affected by the presence or absence of HCO-3 in either segment. Rate of recovery was depressed by Na+ removal in distal-proximal segments only and only in HEPES buffer. It was not affected by removal of Cl- or of both Na+ and Cl- or by reduction in membrane potential through addition of Ba2+ (5 mM) or high K+ (75 mM) in either segment in either HEPES or HEPES-HCO-3 buffer. The Na+/H+ exchange inhibitor ethylisopropylamiloride (EIPA) (100 microM) and the anion exchange inhibitor DIDS (100 microM) reduced dpHi/dt in the distal-proximal segments only and only in HEPES-HCO-3 buffer. The H+-ATPase inhibitor bafilomycin (1 microM), H+-K+-ATPase and K+/NH+4 exchange inhibitor Schering 28080 (10-100 microM), organic cation efflux inhibitor tetrapentylammonium (25 microM-20 mM), and K+ channel blocker tetraethylammonium (20 mM) had no effect on dpHi/dt in either segment. These data do not clearly support basolateral regulation of pHi in snake proximal renal tubules by commonly recognized Na+-dependent or Na+-independent acid or base transporters.

Inhibition of both Na/H and bicarbonate-dependent exchange is required to prevent recovery of intracellular pH in single cardiomyocytes exposed to metabolic stress.

Although tight regulation of intracellular pH (pHi) is critical for the survival under stress, paradoxically a slowed recovery of pHi under hypoxic injury may be cardioprotective. In this study, we investigated the recovery of pHi after hypoxia-induced intracellular acidosis in cardiomyocytes loaded with the H+-sensitive dye SNARF-1. Exposure of single cardiomyocytes to 2,4-dinitrophenol (DNP), an inhibitor of mitochondrial oxidative phosphorylation, induced significant intracellular acidification. However, within 10-12 min upon removal of DNP, cardiomyocytes restituted their intracellular H+ concentration. The presence either of 5-N-ethyl-N-isopropylamiloride (EIPA) an inhibitor of Na/H antiporter, or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of bicarbonate-dependent exchange, did not modify the cellular response to DNP. But, combined use of EIPA and DIDS prevented the restitution of intracellular pH following removal of DNP. This study, thus, demonstrated, for the first time, that blockade of both Na/H and bicarbonate-dependent exchange is necessary and sufficient to maintain the hypoxia-induced intracellular acidification. Therefore, concomitant blockade of both pH-regulating mechanisms deserves to be further considered as a novel strategy against hypoxia-reoxygenation injury in the heart.