Incidental findings during donor liver assessment: Single center experience.

Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18-70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.

Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.

BACKGROUND: The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection. AIMS: To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance. METHODS: Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined. RESULTS: In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies. CONCLUSIONS: Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.

The number and ratio of positive lymph nodes affect pancreatic cancer patient survival after neoadjuvant therapy and pancreaticoduodenectomy.

AIMS: This study is to examine the significance of the number and ratio of positive nodes in post-neoadjuvant therapy pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Our study population consisted of 398 consecutive PDAC patients, who completed neoadjuvant therapy and PD between 1999 and 2012. Lymph node status was classified as ypN0 (node-negative), ypN1 (1-2 positive nodes) and ypN2 (≥3 positive nodes) and correlated with disease-free survival (DFS) and overall survival (OS). The ypN0, ypN1 and ypN2 was present in 183 (46.0%), 117 (29.4%) and 98 (24.6%) patients, respectively. Additionally, 162 (40.7%) had a lymph node ratio (LNR) ≤0.19 and 53 (13.3%) had a LNR >0.19. Patients with ypN1 disease had shorter DFS and OS than those with ypN0 disease, but better DFS and OS than those with ypN2 disease (P < 0.05). Similarly, patients with a LNR ≤ 0.19 had better DFS and OS than those with a LNR > 0.19 (P < 0.001). In multivariate analysis, both the number of positive nodes and LNR were independent prognostic factors for DFS and OS. CONCLUSIONS: Subclassification of post-therapy node-positive group into ypN1 (1-2 positive nodes) and ypN2 (≥3 positive nodes) should be incorporated into the American Joint Committee on Cancer (AJCC) staging of PDAC patients.

Changes in the levels of beta-thromboglobulin and inflammatory mediators during extracorporeal membrane oxygenation support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been associated with platelet dysfunction, but no markers of platelet dysfunction during ECMO have been identified. METHODS: We investigated the potential uses of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) as markers of platelet activation induced by ECMO in vivo. RESULTS: 13 patients who received ECMO for acute respiratory failure were included. Generalized estimating equations were used to examine the associations between days on ECMO and the plasma levels of beta-TG and PF4 and of proinflammatory markers. Analyses were performed before ECMO (baseline) and 24, 48, 72 and 168 hours after the commencement of ECMO. The plasma levels of biomolecules were measured by ELISA and Luminex assay.Percentages of platelets varied widely without statistical significance (p = 0.17). Beta-TG levels significantly decreased over the first 72 hours (p<0.001), but PF4 levels decreased nonsignificantly (p = 0.17). Inflammatory markers, that is, plasma IL-6 (p = 0.03), IL-18 (p<0.001), and MMP-8 (p<0.01) levels stabilized during an early period of ECMO support. CONCLUSIONS: Our data suggest that ECMO use may not affect platelet activation during the first 3 days of ECMO. Plasma beta-TG levels may allow assessment of the time-dependent extent of ECMO-induced platelet dysfunction in patients with acute respiratory failure.

Superior Mesenteric Artery Margin of Posttherapy Pancreaticoduodenectomy and Prognosis in Patients With Pancreatic Ductal Adenocarcinoma.

Negative-margin resection is crucial to favorable prognosis in patients with pancreatic ductal adenocarcinoma. However, the definition of a negative superior mesenteric artery margin (SMAM) varies. The College of American Pathologists defines positive SMAM as the presence of tumor cells at the margin, whereas the European protocol is based on a 1 mm clearance. In this study, we examined the prognostic significance of the SMAM distance in 411 consecutive pancreatic ductal adenocarcinoma patients who completed neoadjuvant therapy and pancreaticoduodenectomy. Per College of American Pathologists criteria, 32 (7.8%) had positive margins, and 379 (92.2%) had negative margins. Among margin-negative group, SMAM was ≤ 1, 1.0 to 5.0, and >5.0 mm in 66, 145, and 168 patients, respectively. There was no difference in either disease-free survival (DFS) or overall survival (OS) between the positive-margin group and SMAM ≤ 1 mm (P > 0.05). However, patients with SMAM 1.0 to 5.0 mm had better OS than those with positive margins or SMAM ≤ 1 mm (P = 0.02). Patients with SMAM > 5.0 mm had better DFS and OS than those with SMAM 1.0 to 5.0 mm and those with positive margins or SMAM ≤ 1 mm (P < 0.01). By multivariate analysis, the SMAM distance, tumor differentiation, lymph node metastasis, and histopathologic tumor response grade were independent prognostic factors for both DFS and OS. SMAM distance correlated with lower ypT and AJCC stages, smaller tumor size, better histopathologic tumor response grade, fewer lymph node metastases, and recurrences (P < 0.05). Thus our results strongly support use of SMAM > 1 mm for R0 resection in posttherapy pancreaticoduodenectomy specimens.

Doxorubicin-polyphosphazene conjugate hydrogels for locally controlled delivery of cancer therapeutics.

Poly(organophosphazene)-doxorubicin (DOX) conjugate bearing hydrophobic L-isoleucine ethyl ester (IleOEt) and hydrophilic alpha-amino-omega-methoxy-poly(ethylene glycol) with molecular weight of 550 Da (AMPEG 550) along with carboxylic acid as a functional group was synthesized to create a drug delivery system, which is based on locally injectable, biodegradable, and thermosensitive hydrogels. In addition to the evaluation of the in vitro and in vivo antitumor activities, the physicochemical properties, hydrolytic degradation, and DOX release profile of the poly(organophosphazene)-DOX conjugate were determined. The aqueous solution of the polymer-DOX conjugate showed a sol-gel transition behavior depending on temperature changes. Based on the in vivo antitumor activities of the locally injected poly(organophosphazene)-DOX conjugate into the tumor-induced nude mice, the conjugate hydrogel after the local injection at the tumor site was shown to inhibit tumor growth more effectively with less toxicity and much longer than doxorubicin and saline as controls, indicating that tumor active DOX from the conjugate hydrogel is released slowly over a longer period of time and effectively accumulated locally in the tumor sites. These results suggest that the poly(organophosphazene)-doxorubicin conjugates hold great potential for use in preclinical and clinical studies as single and/or combination therapies.

Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis.

BACKGROUND: Prostaglandins, synthesized by cyclooxygenase (COX), play an important role in the pathophysiology of inflammation. Severe injuries result in immunosuppression, mediated, in part, by maladaptive changes in macrophages. Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on liver function and damage after trauma and sepsis. MATERIALS AND METHODS: To ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received sham operations. After 24 h, liver samples were obtained, and mRNA and protein expression were determined by PCR, Western blot, and immunohistochemistry. Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT) levels were determined to assess liver function and damage, respectively. One-way analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess statistical significance. RESULTS: After CLP alone, FFx+CLP, and GdCl3+FFx+CLP, clearance of ICG decreased. Plasma ALT levels increased in parallel with severity of injury. Kupffer cell depletion attenuated the increased ALT levels after FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By contrast, COX-2 protein increased after CLP and was potentiated by sequential stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be Kupffer cells. CONCLUSIONS: In this study, sequential stress increased hepatic COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways may contribute to the inflammatory response leading to increased mortality after sequential stress.