Bibek Aryal

A Switch in the Dynamics of Intra-Platelet VEGF-A from Cancer to the Later Phase of Liver Regeneration after Partial Hepatectomy in Humans

Background Liver regeneration (LR) involves an early inductive phase characterized by the proliferation of hepatocytes, and a delayed angiogenic phase distinguished by the expansion of non-parenchymal compartment. The interest in understanding the mechanism of LR has lately shifted from the proliferation and growth of parenchymal cells to vascular remodeling during LR. Angiogenesis accompanied by LR exerts a pivotal role to accomplish the process. Vascular endothelial growth factor (VEGF) has been elucidated as the most dynamic regulator of angiogenesis. From this perspective, platelet derived/Intra-platelet (IP) VEGF-A should be associated with LR. Material and Methods Thirty-seven patients diagnosed with hepatocellular carcinoma and undergoing partial hepatectomy (PH) were enrolled in the study. Serum and IP VEGF-A was monitored preoperatively and at four weeks of PH. Liver volumetry was determined on computer models derived from computed tomography (CT) scan. Results Serum and IP VEGF-A was significantly elevated at four weeks of PH. Preoperative IP VEGF-A was higher in patients with advanced cancer and vascular invasion. Postoperative IP VEGF-A was higher after major liver resection. There was a statistically significant correlation between postoperative IP VEGF-A and the future remnant liver volume. Moreover, the soluble vascular endothelial growth factor receptor-1 (sVEGFR1) was distinctly down-regulated suggesting a fine-tuned angiogenesis at the later phase of LR. Conclusion IP VEGF-A is overexpressed during later phase of LR suggesting its implications in inducing angiogenesis during LR.

HMGB1 is secreted by 3T3-L1 adipocytes through JNK signaling and the secretion is partially inhibited by adiponectin

Obesity is a chronic inflammatory disease, and adipocytes contribute to obesity‐associated inflammation by releasing inflammatory mediators. High mobility group box 1 (HMGB1), a highly conserved DNA‐binding protein, mainly localized to cell nuclei, has been recently recognized as an innate pro‐inflammatory mediator when released extracellularly. It was hypothesized that HMGB1 is an adipocytokine that acts as an innate pro‐inflammatory mediator in white adipose tissue (WAT) of patients with obesity and is associated with insulin resistance. Additionally, it was hypothesized that HMGB1 secretion is regulated by adiponectin.

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

Purpose: Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth stimulatory effect on several types of carcinoma and tumor cells. Since a large portion of 5-HT is stored and transported by platelets, the aim of this study was to assess the influence of platelet-sequestered 5-HT on post-resection hepatocellular carcinoma (HCC) recurrence. Methods: This pilot study was conducted in a cohort of forty patients diagnosed with HCC undergoing partial hepatectomy. 5-HT levels in serum, plasma and intra-platelet (IP) were monitored preoperatively and four weeks after liver resection. The patients were followed every three months after the surgery. Results: Follow-up was standardized to a fixed length of time. Fifteen patients (37.5%) developed HCC recurrence during 18 months follow-up. Patients with recurrence had significantly reduced serum and IP 5-HT levels at four weeks of liver resection (P = 0.003 and P = 0.014 respectively). Accordingly, in the Cox regression hazard model, serum and IP 5-HT were able to independently predict the recurrence (hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.75 and hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.89 respectively). The optimal cut-off value of 42.77 ng/ml for serum [area under the curve (AUC): 0.78, P = 0.003] and 0.3117 ng per 106 platelets (AUC: 0.733, P = 0.015), on receiver operating characteristic (ROC) curve corresponded to maximum sensitivity and specificity of prediction. The disease free interval was significantly worse in patients with low serum and IP 5-HT (P = 0.001 and P = 0.029 respectively). Conclusion: IP 5-HT monitored during early follow-up, after liver resection may represent a useful marker of early HCC recurrence.

Middle-preserving pancreatectomy with reversed pancreaticogastrostomy: report of a case

Parenchyma-sparing pancreatic resections have been reported increasingly in recent years; however, for multifocal diseases involving the head and the tail of the pancreas, total pancreatectomy is still the preferred procedure. The possible consequence of this procedure is loss of normal pancreatic parenchyma, resulting in insufficiency of pancreatic exocrine and endocrine functions. Various types of limited resection have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor. Even for multifocal diseases, if the pancreatic body is spared, a middle-preserving pancreatectomy (MPP) can be performed to assure maximal pancreatic function and uncompromised quality of life. Yet, few papers have introduced the feasibility of MPP for a better outcome. This report describes a new surgical technique for MPP using an alternative approach for the remnant pancreas anastomosis. We used this technique successfully to remove a bifocal neoplasm: adenocarcinoma of the distal bile duct and mucinous cyst adenoma in the tail of the pancreas.

Deciphering Platelet Kinetics in Diagnostic and Prognostic Evaluation of Hepatocellular Carcinoma

Liver pathophysiology can, directly and indirectly, impose morphological or biochemical abnormalities of the platelets. Conversely, platelets are also able to regulate the promitogenic and profibrotic signals on liver pathobiology. Platelet contribution to the liver pathophysiology is typically facilitated by the platelet-derived growth factors that are sequestered in different subsets of alpha and dense granules, and the release of these growth factors is synchronized according to the stage and type of liver disease or injury. Thus, platelets harbor clinically relevant information with potential diagnostic and prognostic implications in liver diseases. Hepatocellular carcinoma (HCC) largely influences the platelet kinetics, and a growing body of evidence has recognized its association with HCC occurrence or prognosis. This narrative review summarizes the progress made on implicating platelet as a diagnostic and prognostic tool for HCC; the review also dissects the contradictory results from earlier studies and reflects how combining platelet-based information may enable more reliable test for diagnostic and prognostic evaluation of HCC.

First jejunal artery, an alternative graft for right hepatic artery reconstruction

Common bile duct cancer invading right hepatic artery is sometimes diagnosed intraoperatively. Excision and safe reconstruction of the artery with suitable graft is essential. Arterial reconstruction with autologous saphenous vein graft is the preferred method practiced routinely. However the right hepatic artery reconstruction has also been carried out with several other vessels like gastroduodenal artery, right gastroepiploic artery or the splenic artery. We report a case of 63-year-old man presenting with history of progressive jaundice, pruritus and impaired appetite. Following various imaging modalities including computed tomography, endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography, intraductal ultrasound extrahepatic bile duct cancer was diagnosed; however, none of those detected vessel invasion. Intraoperatively, right hepatic artery invasion was revealed. Right hepatic artery was resected and reconstructed with a graft harvested from the first jejunal artery (JA). Postoperative outcome was satisfactory with a long-term graft patency. First JA can be a reliable graft option for right hepatic artery reconstruction.

Therapeutic implication of platelets in liver regeneration –hopes and hues

ABSTRACT Introduction: Mounting evidence highlights platelet involvement in liver regeneration via interaction with liver cells, growth factors release, and signaling contributions. Existing research suggests a compelling biological rationale for utilizing platelet biology, with the goal of improving liver function and accelerating its regenerative potential. Despite its expanding application in several clinical areas, the contribution of the platelet and its therapeutic implementation in liver regeneration so far has not yet fulfilled the initial high expectations. Areas covered: This review scrutinizes the progress, current updates, and discusses how recent understanding – particularly in the clinical implications of platelet-based therapy – may enable strategies to introduce and harness the therapeutic potential of the platelet during liver regeneration. Expert commentary: Several clinical and translational studies have facilitated a platform for the development of platelet-based therapy to enhance liver regeneration. While some of these therapies are effective to augment liver regeneration, the others have had some detrimental outcomes. The existing evidence represents a challenge for future projects that are focused on directly incorporating platelet-based therapies to induce liver regeneration.

Conquering the deadly stroke: Perspective on a surgeon's odyssey

Highlights • An odyssey of a Japanese surgeon, who survived a life-threatening hemorrhagic stroke.• Self-motivation and adherence to work ethics displayed by the surgeon to return to work is admirable.• Passion is a detrimental factor that enables surgeons to overcome a roadblock to their career.