Modified Appleby Procedure with Arterial Reconstruction for Locally Advanced Pancreatic Adenocarcinoma: A Literature Review and Report of Three Unusual Cases.

BACKGROUND: Pancreatic body and tail ductal adenocarcinomas are often diagnosed with local vascular invasion of the celiac axis (CA) and its various branches. With such involvement, these tumors have traditionally been considered unresectable. The modified Appleby procedure allows for margin negative resection of some such locally advanced tumors. This procedure involves distal pancreatectomy with en bloc splenectomy and CA resection and relies on the presence of collateral arterial circulation via an intact pancreaticoduodenal arcade and the gastroduodenal artery to maintain prograde hepatic arterial perfusion. When the resultant collateral circulation is inadequate to provide sufficient hepatic and gastric arterial inflow, arterial reconstruction (AR) is necessary to supercharge the inflow. Herein, we review all reported cases of AR with modified Appleby procedures that we have identified in the literature, and we report our experience of three recent cases with arterial reconstruction including two cases with arterial bypasses not requiring interposition grafting. METHODS: Perioperative and oncologic outcomes from our Institutional Review Board-approved database of pancreatic resections at the Thomas Jefferson University were reviewed. Additionally, PubMed search for cases of distal or total pancreatectomy with celiac axis resection and concurrent AR was performed. RESULTS: From the literature, 12 reports involving 28 patients were identified of distal and total pancreatectomy with AR after CA resection. The most common AR in the literature, performed in 12 patients, was a bypass from the aorta to the common hepatic artery (CHA) using a variety of interposition conduits. In our institutional experience, patient #1 had a primary side-to-end aorto-CHA bypass, patient #2 had a primary end-to-end bypass of the transected distal CHA to the left gastric artery in the setting a replaced left hepatic artery, and patient #3 required an aortic to proper hepatic artery bypass with saphenous vein graft and portal venous reconstruction. All patients recovered from their operations without ischemic complications, and they are currently 16, 15, and 13 months post-op, respectively. CONCLUSIONS: The criteria for resectability in patients with locally advanced pancreatic body and tail neoplasms are expanding due to increasing experience with AR in the setting of the modified Appleby procedure. When performing AR, primary arterial re-anastomosis may be considered preferable to interposition grafting as it decreases the potential for the infectious and thrombotic complications associated with conduits and it reduces the number of vascular anastomoses from two to one. Consideration must also be given to normal variant anatomy of the hepatic circulation during operative planning as the origin of the left gastric artery is resected with the CA. The modified Appleby procedure with AR, when used in appropriately selected patients, offers the potential for safe, margin negative resection of locally advanced pancreatic body and tail tumors

Robotic-assistance does not enhance standard laparoscopic technique for right-sided donor nephrectomy.

OBJECTIVE: To examine donor and recipient outcomes after right-sided robotic-assisted laparoscopic donor nephrectomy (RALDN) compared with standard laparoscopic donor nephrectomy (LDN) and to determine whether robotic-assistance enhances LDN. MATERIALS & METHODS: From December 2005 to January 2011, 25 patients underwent right-sided LDN or RALDN. An IRB-approved retrospective review was performed of both donor and recipient medical charts. Primary endpoints included both intraoperative and postoperative outcomes. RESULTS: Twenty right-sided LDNs and 5 RALDNs were performed during the study period. Neither estimated blood loss (76.4 mL vs. 30 mL, P = .07) nor operative time (231 min vs. 218 min, P = .61) were significantly different between either group (LDN vs. RALDN). Warm ischemia time for LDN was 2.6 min vs. 3.8 min for RALDN (P = .44). Donor postoperative serum estimated glomerular filtration rates (eGFR) were similar (53 vs. 59.6 mL/min/1.73 m2, LDN vs. RALDN, P = .26). For the recipient patients, posttransplant eGFR were similar at 6 months (53.4 vs. 59.8 mL/min/1.73 m2, LDN vs. RALDN, P = .53). CONCLUSION: In this study, robotic-assistance did not improve outcomes associated with LDN. Larger prospective studies are needed to confirm any perceived benefit of RALDN

Hepatocellular Carcinoma Treated with Microwave Ablation Prior to Liver Transplantation

Introduction: Ablation is a minimally invasive procedure that limits local liver tumor progression and prolongs patients’ transplantation eligibility. Microwave ablation (MWA) utilizes higher temperatures than the standard of care, radiofrequency ablation (RFA), which increases efficiency. Meta-analyses compared MWA with RFA for the treatment of HCC and showed similar efficacy and safety between these modalities. However, limited pathologic data exists determining whether explanted tumors remained viable after MWA. Methods: Our database was reviewed retrospectively for patients with HCC who underwent MWA prior to liver transplantation between 2013 and 2019. Patient demographics, etiology of disease, tumor size, procedure details, bilirubin, MELD, and Child-Pugh score were reviewed. Tumors were classified as viable or nonviable based on pathology. Imaging and clinical follow-up were available for surveillance and post-transplant. Results: 29 patients (23 males, 6 females) with 40 tumors underwent MWA. The average patient age was 60 years. The mean tumor size was 2.2 cm (range 1-3.7). Twenty-six patients were alive at follow-up. Pathological analysis showed 38 of the 40 tumors ablated to be non-viable at explant. Imaging prior to transplant reported one case with recurrent tumor at the ablation site and another case as equivocal. No cases of metastatic HCC were identified by imaging post-transplant. Discussion: Previous studies have not included this pathologic data. Determining tumor viability provides valuable information regarding whether tumors are likely to recur locally, even after transplantation. These results suggest that MWA is an effective treatment of small HCC prior to transplant with a low incidence of local tumor recurrence

The adipose tissue production of adiponectin is increased in end-stage renal disease.

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease

Transplantation of Kidneys from Donors with Acute Renal Failure Five-Year Results from Double Center Experience

Background: Transplantation of kidneys from deceased donors with acute renal failure (ARF) has been described and represents an underutilized source of renal grafts. We reviewed retrospectively our double center experience with transplantation of ARF donor kidneys. Methods: Between January 2009 and June 2014, we performed a total of 397 kidney transplants at the two hospitals. Of which, 65 came from donors with ARF. The outcome was compared with 62 expanded criteria donor kidneys and 270 standard criteria donor kidneys. ARF was defined as donor terminal creatinine higher than 2. All kidneys from ARF donors had acceptable biopsies and were pumped. The immunosuppression was similar in all three groups (Thymoglobulin for induction and Prograf, Cellcept and steroids for maintenance). The outcome measurements included recipient serum creatinine, patient and graft survival at 6 months, 1 year and 3 years. We also reviewed the delayed graft function (DGF) rates and cold ischemic time in all groups. Results: Mean donor creatinine was 3.84±1.3. The 6 month, 1 and 3 year patient survival rates were 98.5%, 96.8% and 92.0% in ARF group, 98.1%, 97.0% and 93.4% SCD group and 98.4%, 93.2% and 77.7% in ECD group. The 6 month, 1 and 3 year death censored graft survival was 96.9%, 96.9%, 96.9% in ARF group, 97.7, 96.5, 91.8 in SCD group and 95.1%, 93.2%, 90.1% in ECD group. The mean 6mo, 1 year and 3 year recipient creatinine was 1.49, 1.46 and 1.51 in ARF group, 1.61, 1.72 and 1.77 in SCD group and 1.91, 1.92 and 2.15 in ECD group, respectively. ARF kidneys are noted to be associated with more DGF (58.5% in ARF group VS 41.5% in non ARF group), longer cold ischemic time (857.79 min in ARF group vs 589.32 min in non ARF group) and younger donor age (32.25 years in ARF group vs 40.65 years in non ARF group). Conclusion: Elevated terminal donor creatinine is not a risk factor for graft loss after deceased donor kidney transplantation. Although there is increased risk of DGF and longer cold ischemic time, transplantation of ARF kidneys provides comparable short and long term graft function and patient survival compared to kidneys from non ARF donors

Image analysis for classification of dysplasia in Barrett’s esophagus using endoscopic optical coherence tomography

Barrett’s esophagus (BE) and associated adenocarcinoma have emerged as a major health care problem. Endoscopic optical coherence tomography is a microscopic sub-surface imaging technology that has been shown to differentiate tissue layers of the gastrointestinal wall and identify dysplasia in the mucosa, and is proposed as a surveillance tool to aid in management of BE. In this work a computer-aided diagnosis (CAD) system has been demonstrated for classification of dysplasia in Barrett’s esophagus using EOCT. The system is composed of four modules: region of interest segmentation, dysplasia-related image feature extraction, feature selection, and site classification and validation. Multiple feature extraction and classification methods were evaluated and the process of developing the CAD system is described in detail. Use of multiple EOCT images to classify a single site was also investigated. A total of 96 EOCT image-biopsy pairs (63 non-dysplastic, 26 low-grade and 7 high-grade dysplastic biopsy sites) from a previously described clinical study were analyzed using the CAD system, yielding an accuracy of 84% for classification of non-dysplastic vs. dysplastic BE tissue. The results motivate continued development of CAD to potentially enable EOCT surveillance of large surface areas of Barrett’s mucosa to identify dysplasia

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Combined US-triggered microbubble destruction and hepatocellular carcinoma radioembolization showed improved treatment response compared with radioembolization alone and no changes in vital signs or liver function. Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P \u3e .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response

Neptune to the Common-wealth of England (1652): the republican Britannia and the continuity of interests

In the seventeenth century, John Kerrigan reminds us, “models of empire did not always turn on monarchy”. In this essay, I trace a vision of “Neptune’s empire” shared by royalists and republicans, binding English national interest to British overseas expansion. I take as my text a poem entitled “Neptune to the Common-wealth of England”, prefixed to Marchamont Nedham’s 1652 English translation of Mare Clausum (1635), John Selden’s response to Mare Liberum (1609) by Hugo Grotius. This minor work is read alongside some equally obscure and more familiar texts in order to point up the ways in which it speaks to persistent cultural and political interests. I trace the afterlife of this verse, its critical reception and its unique status as a fragment that exemplifies the crossover between colonial republic and imperial monarchy at a crucial moment in British history, a moment that, with Brexit, remains resonant

Transmission of Yellow Fever Vaccine Virus Through Blood Transfusion and Organ Transplantation in the USA in 2021: Report of an Investigation

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases