Liver innervation and hepatic function: new insights.

The hepatic nervous system has a well-known impact on the regulation of liver function and organism homeostasis. The aim of this review is to summarize the new available data regarding the role of hepatic nerves. In the last decade, studies have shown that hepatic nerves exert subtle but significant modifications on the regulation of glucose and lipid metabolism, food intake, and liver regeneration. They also play a role in liver disease pathogenesis, and hepatic denervation has beneficial results to liver graft ischemia-reperfusion injury. Available data are still limited, and further research toward neural pathways involving the liver that can modify response to disease is required.

Liver regeneration: immunohistochemical study of intrinsic hepatic innervation after partial hepatectomy in rats.

BACKGROUND: We examined the intrinsic hepatic innervation after partial hepatectomy (PH) in rats and the presence and pattern of neural sprouting in regenerating liver. METHODS: Male Wistar rats (age 9-13 weeks-w, weight 204-356 g), were submitted to two-thirds PH. Rats were sacrificed at postoperative days (d) 1, 3, 5, 7, at 2 and 4 w, and at 3 and 6 months (m) (6-7 animals/group, control group n = 4). Immunohistochemistry for the pan-neural marker protein gene product 9.5 (PGP9.5) and growth-associated protein 43 (GAP-43), a marker of regenerating nerve axons, was performed on tissue sections from the R1 lobe of the regenerating liver. Portal tracts (PTs) with immunoreactive fibers were counted in each section and computer-assisted morphometric analysis (Image Pro Plus) was used to measure nerve fiber density (number of immuno-positive nerve fibers/mm2 (40x)). RESULTS: Immunoreactivity for PGP9.5 was positive in all groups. The number of PGP9.5 (+) nerve fibers decreased from 0.32 +/- 0.12 (control group) to 0.18 +/- 0.09 (1d post-PH group), and gradually increased reaching pre-PH levels at 6 m (0.3 +/- 0.01). In contrast, immunoreactivity for GAP-43 was observed at 5d post-PH, and GAP-43 (+) PTs percentage increased thereafter with a peak at 3 m post-PH. GAP-43 (+) nerve fiber density increased gradually from 5d (0.05 +/- 0.06) with a peak at 3 m post-PH (0.21 +/- 0.027). At 6 m post-PH, immunoreactivity for GAP-43 was not detectable. CONCLUSIONS: Following PH in rats: 1) nerve fiber density in portal tracts decreases temporarily, and 2) neural sprouting in the regenerating liver lobes starts at 5d, reaches peak levels at 3 m and disappears at 6 m post-PH, indicating that the increase in hepatic mass after PH provides an adequate stimulus for the sprouting process.

Residual lymph node disease and mortality following neoadjuvant chemoradiation and curative esophagectomy for distal esophageal adenocarcinoma.

Objectives: Neoadjuvant chemoradiation has been shown to improve survival in locally advanced esophageal and gastroesophageal junction cancer. The purpose of our study was to examine the effects of posttreatment persistent lymph node (LN) disease on overall survival (OS) and recurrence in patients with esophageal adenocarcinoma after neoadjuvant chemoradiation as well as the effect of LN harvest and the potential benefit of adjuvant chemotherapy. Methods: The records of patients who underwent esophagectomy in our hospital from January 2005 until December 2016 were analyzed. Our study group consisted of 509 patients. Results: Patient groups were created based on pathologic staging after esophagectomy (ypT N) as 22.0% of patients were ypT0 N0, 46.2% had incomplete response only at the primary tumor level (ypT + N0), and 31.8% had at least 1 metastatic lymph node (ypTx N+). Median OS was 58.3 months. The ypTx N+ group was divided into ypTx N1 and ypTx N2 or N3 subgroups based on the number of metastatic lymph nodes. The OS between the 2 groups was not significantly different (median OS, 37.6 vs 29.8 months; P = .097). The disease-free survival did show a statistically significant difference (median disease-free survival, 27.6 vs 13.7 months; P = .007). The LN harvest was not found to be significantly associated with OS. However, administration of adjuvant chemotherapy was a significant prognosticator for increased OS (hazard ratio, 0.590; P = .043). Conclusions: Our results demonstrate that residual LN disease after neoadjuvant chemoradiation is associated with increased mortality. Adjuvant chemotherapy, but not number of LNs resected, was correlated with increased OS in this subset of patients.

Tityus: a forgotten myth of liver regeneration.

The ancient Greek myth of Tityus is related to liver regeneration in the same way as the well known myth of Prometheus is. Depictions of the punishment of Prometheus are frequently used by lecturers on liver regeneration; however, Tityus remains unknown despite the fact that he received the same punishment and his myth could also be used as a paradigm for the organ's extraordinary ability to regenerate. Nevertheless, there is no convincing evidence that ancient Greeks had any specific knowledge about liver regeneration, a concept introduced in the early 19th century. We describe and analyze the myth of Tityus and compare it to the myth of Prometheus. We also explore artistic and literary links and summarize recent scientific data on the mechanisms of liver regeneration. Finally, we highlight links of the legend of Tityus with other sciences.

Liver regeneration: focus on cell types and topographic differences.

BACKGROUND/AIMS: The liver has a remarkable capacity to regenerate after injury or resection. The aim of the current review is to outline the morphological changes at the cellular level and the intralobular differences during the regenerative response after partial hepatectomy. METHODS: Relevant studies were reviewed using the Medline database. RESULTS: At 24 h after partial hepatectomy, many alterations between the periportal and pericentral regions of the hepatic lobule occur, which coincide with the peak of hepatocellular proliferation in the periportal areas. Questions unanswered involve the precise role of Kupffer cells and whether the regenerative process is characterized by a net increase in the number of lobules or by an increase in the size of the existing lobules. CONCLUSIONS: Liver regeneration has been studied for many years, but further research is essential, since in-depth knowledge of the mechanisms that govern the regenerative process may expand the treatment options in patients with hepatic disease.

Distal pancreatectomy outcomes: Perspectives from a community-based teaching institution.

BACKGROUNDS/AIMS: Distal pancreatic resections are intricate operations with potential for significant morbidity; there is controversy surrounding the appropriate setting regarding surgeon/hospital volume. We report our distal pancreatectomy experience from a community-based teaching hospital. METHODS: This study includes all patients who underwent laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for benign and malignant lesions between June 2004 and October 2017. Both groups were compared for perioperative characteristics, parenchymal resection technique, and outcomes. RESULTS: 138 patients underwent distal pancreatectomy during this time. The distribution of LDP and ODP was 68 and 70 respectively. Operative time (146 vs. 174 min), blood loss (139 vs. 395 ml) and mean length of stay (4.8 vs. 8.0 days) were significantly lower in the laparoscopic group. The 30-day Clavien Grade 2/3 morbidity rate was 13.7% (19/138) and the incidence of Grade B/C pancreatic fistula was 6.5% (9/138), with no difference between ODP and LDP. 30-day mortality was 0.7% (1/138). 61/138 resections had a malignancy on final pathology. ODP mean tumor diameter was greater (6.4 cm vs. 2.9 cm), but there was no significant difference in the mean number of harvested nodes (8.6 vs. 7.4). The cost of hospitalization, including readmissions and surgery was significantly lower for LDP ($7558 vs. $11610). CONCLUSIONS: This series of distal pancreatectomies indicates a shorter hospital stay, less operative blood loss and reduced cost in the LDP group, and comparable morbidity and oncologic outcomes between LDP and ODP. It highlights the feasibility and safety of these complex surgeries in a community setting.

Salvage of a Live-Related Transplant Kidney Using an Interposition Polytetrafluoroethylene Vascular Graft: A Unique Case.

We describe a case of polytetrafluoroethylene vascular graft interposition between the internal iliac artery and the renal artery in a live-related kidney transplant. To the best of our knowledge, we present the first case in the literature that describes the salvage of a transplant kidney using this technique.

Rescue of Transplanted Kidney Thanks to an Implantable Doppler Probe: Is This the Future?

Observing graft blood supply post kidney transplantation is essential. Compromised graft perfusion must be identified without delay to preserve organ survival. Implantable probes have revolutionised the graft monitoring process in kidney transplantation leading to safe, continuous, and distinct monitoring of blood supply. The Implantable Cook-Swartz Doppler Flow Monitoring System allows immediate salvaging of a compressed kidney. The implantable Doppler probe can easily and effectively identify such cases and save the limited number of organs that are available to today's patients.

Surgical Stapler for Right Renal Vein Elongation Using the Inferior Vena Cava in Kidney Transplant.

Elongation of the right renal vein with the inferior vena cava (caval patch) using a vascular stapler offers a safe means of extending the deceased-donor right renal vein, while minimizing the ischemic time of the kidney during preparatory dissection. The aortic patch of the right renal artery also can be preserved, which minimize the danger of arterial stenosis, kinking, and dissection.

Paratransplant Hernia: A True Emergency After Renal Transplant.

We report a case of paratransplant hernia, a rare surgical complication of a renal transplant. It is caused by entrapment of the bowel through a defect in the peritoneum, which lines on the transplanted kidney. Careful dissection and meticulous surgical technique during transplant, closing any peritoneal defect, regardless of size, can avoid this complication. The prognosis depends on clinical suspicion, prompt diagnosis, and early surgical intervention. If strangulation occurs, the associated mortality is high.

Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury?

INTRODUCTION: The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the treatment of ischemia-reperfusion injury (IRI). AREAS COVERED: Data were reviewed from the published literature using the Medline database. The effect of PIs on IRI is dependent on the dosage, time of administration (prior to or post IRI induction), the affected organ, and the experimental model used. Undoubtedly, in most cases PIs' application resulted in attenuated IRI, although it was uniformly shown that inhibition of the UPS prior to ischemic preconditioning (IPC) abolished the protective effect of IPC in IRI. Mechanism of action involves several pathways, including nuclear factor kappa-B (NF-κB) inactivation, antineutrophil action, decreased intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, and the cytoprotective proteins eNOS, heme oxigenase 1 and hsp70 up-regulation. EXPERT OPINION: Current data are limited, but appear promising with regard to PI consideration as an effective future therapeutic strategy for IRI. Nevertheless, further investigation is required in terms of safety and validation of the appropriate for each agent dosage, in order to establish their possible contribution in human IRI.

A Case of Retroperitoneal Castleman's Disease and an Update on the Latest Evidence.

Castleman's disease is a benign lymphoproliferative condition with three distinct histological subtypes. Clinically it presents in either a unicentric or multicentric manner and can affect various anatomic regions, the mediastinum being the most frequent location. We herein present a rare case of unifocal retroperitoneal mass proved to be hyaline vascular Castleman's disease. We perform a review of the current literature pertaining to such lesions, focusing on the management of the various clinical and histological variants of the disease. Surgical excision is the treatment of choice for unifocal Castleman's disease.