Inhibition of RIPK1-dependent regulated acinar cell necrosis provides protection against acute pancreatitis via the RIPK1/NF-κB/AQP8 pathway.

Currently, preliminary results have confirmed the existence of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL)-dependent necroptosis of pancreatic acinar cells during early acute pancreatitis (AP), which might be a potential target for the effective regulation of necroinflammatory injury. However, the exact effect of receptor-interacting protein kinase 1 (RIPK1)-dependent regulated acinar cell necrosis on AP is still uncertain. In our study, we first explored the changes in the degree of local and systemic inflammation in AP rats when the activation of acinar cell RIPK1 was inhibited. The RIPK1 inhibitor Nec-1 was used to treat rats, and the levels of related inflammatory markers, necrosis indicators and apoptotic indicators were measured. Changes in pancreatic nuclear factor κB (NF-κB) and aquaporin 8 (AQP8) expression were noted. Next, the expression of AQP8 in AR42J cells was inhibited, and the degree of cell necrosis and inflammatory damage was found to be significantly reduced. Most importantly, we demonstrated that the RIPK1/NF-ĸB/AQP8 axis might be a potential regulatory pathway mediating RIPK1-dependent regulated acinar cell necrosis in early AP. Finally, we used the NF-κB inhibitor PDTC and Nec-1 to treat rats in different groups and measured the degree of pathological pancreatic injury, the activation of RIPK1, and the expression of NF-κB and AQP8. In summary, we hypothesized that there might be a RIPK1/NF-ĸB/AQP8 pathway controlling RIPK1-dependent regulated necrosis of acinar cells in AP, which might be a promising therapeutic target against AP-related injury.

Acute pancreatitis induced by etoposide-lobaplatin combination chemotherapy used for the treatment of lung cancer: A case report and literature review.

RATIONALE: Drug-induced pancreatitis (DIP) is a rare type of pancreatitis that is not usually observed in the clinical practice. It is generally difficult to distinguish from acute pancreatitis (AP) induced by other causes. PATIENT CONCERNS: Here, we report a 62-year-old Chinese female patient with "small cell lung cancer" as the initial presentation. Because the patient could not bear the surgical treatment, the chemotherapy composed of lobaplatin and etoposide was performed. Three days later, the patient displayed sudden abdominal pain, distension, nausea, and vomiting without obvious inducements. Laboratory tests showed that the levels of serum and urine amylase were enhanced; abdominal computed tomography (CT) result showed the enlargement of the pancreas, peripancreatic effusion, and a rough edge, which suggested the diagnosis of AP. The patient had no history of biliary tract disease, alcoholism, binge overeating, hyperlipidemia, and hereditary pancreatitis. DIAGNOSES: The patient was diagnosed with DIP. INTERVENTIONS: The chemotherapy was stopped at once and we performed fluid resuscitation, pain alleviation, prophylactic antibiotics, and nutritional support, etc on the patient. Later, the patient's clinical symptoms were obviously relieved, and she recovered successfully. OUTCOMES: The chemotherapy was continued, but later, the patient showed abdominal pain, distension, nausea, and vomiting again. The levels of serum amylase and urine amylase were enhanced again. Further imaging examination strongly indicated the recurrence of AP. LESSONS: We should raise awareness of the clinicians regarding DIP, thereby enabling its timely diagnosis and accurate treatment, as well as promoting the rational and safe use of drugs.

Anatomic Characteristics, Identification, and Protection of the Nonrecurrent Laryngeal Nerve during Thyroidectomy.

Objective We aimed to investigate the anatomical features and variation pattern of the nonrecurrent laryngeal nerve (NRLN), summarize the methods for identifying the NRLN before and during thyroidectomy, and share experiences regarding preventing and treating its injury. Study Design Retrospective case data analysis. Setting First Affiliated Hospital of Harbin Medical University. Subjects and Methods Between January 2002 and May 2016, 7392 patients underwent thyroidectomy in our hospital. Of them, 28 patients with NRLN were identified, and their clinical data were retrospectively analyzed. Results This study included 7392 patients in which the recurrent laryngeal nerves (RLNs) were routinely identified during surgery. The presence of NRLN was intraoperatively confirmed in 28 patients. All the NRLNs were located on the right side and its overall incidence was 0.37%. Five of the NRLNs were classified as type I, 19 as type IIa, and 4 as type IIb. Of the 28 cases, 4 NRLNs were injured during surgery, in which primary end-to-end anastomosis or local seal with corticosteroid injection was performed as a remedy. In the 4 patients with NRLN injury, 2 presented with postoperative hoarseness that indicated vocal cord paralysis confirmed by laryngoscope; the other 2 patients' voices had no significant changes. Conclusion The NRLN, which is rare in clinical practice and predominantly right-sided, is anatomically more complex and variant at a higher risk of surgical injury. The key factors to accurately identify NRLN and to effectively prevent its injury include careful interpretation of auxiliary examination results before surgery, raising awareness of its presence, meticulous dissection, and routine exposure of the RLN during surgery.

Acinar cell cystadenoma of the pancreas: A retrospective analysis of ten-year experience from a single academic institution.

BACKGROUND/OBJECTIVE: Acinar cell cystadenoma (ACA), also referred to as "acinar cystic transformation", is a rare and newly recognized cystic lesion of the pancreas displaying apparent acinar cell differentiation with benign outcomes. We summarized our experience with the diagnosis, clinicopathologic feature, treatment and prognosis of ACA to provide a reference for the disposal of this uncommon condition. METHODS: We retrospectively analyzed the clinical data from eight patients with ACA treated in our hospital between March, 2005 and January, 2015. RESULTS: Among eight patients, five of whom were female and the age at diagnosis ranged from 33 to 67 years (mean, 49.8 y). The most commonly clinical symptom was abdominal pain. Eight lesions were unifocal and either unilocular (n = 5) or multilocular (n = 3) with average size of 10.5 cm (range, 5.1-19.7 cm). All the patients were treated surgically and a definite diagnosis of ACA was obtained by the histopathological, histochemical and immunohistochemical tests. The length of stay range was from 11 to 17 days and there were no perioperative deaths. At a median follow-up of 57.3 months, all the patients were alive and there was no evidence of recurrence, distant metastasis or malignant transformation. CONCLUSIONS: Appropriately preoperative differential diagnosis of ACA remains challenging and the final result is usually gained by the histopathology and immunohistochemistry. Although the origin of ACA is still contradictory, surgery is actively advocated as the most effective method for relieving the symptoms and preventing the tumor from local extension or malignant transformation so as to obtain an optimal long-term survival.

External Versus Internal Pancreatic Duct Drainage for the Early Efficacy After Pancreaticoduodenectomy: A Retrospectively Comparative Study.

PURPOSE: To compare the early efficacy of external versus internal pancreatic duct drainage after pancreaticoduodenectomy (PD), providing clinical evidence for selecting the optimal approach to pancreatic duct drainage. MATERIAL AND METHODS: The clinical data of 395 consecutive patients undergoing PD from 2006 to 2013 were analyzed retrospectively. All the patients were divided into external and internal drainage group. Intraoperative blood loss, surgery duration, postoperative hospitalization duration, mortality rate, PF, and other complications were compared between the two groups. The perioperative relative risk factors that might induce PF were analyzed. RESULTS: External drainage significantly reduced the incidences of post-PD PF, delayed gastric emptying, abdominal infection, bowel obstruction, overall complications, and shortened the healing time of PF (p < .05). The univariate analysis showed that the pancreatic duct drainage method, body mass index (BMI), preoperative serum bilirubin level, perioperative blood transfusion, pancreaticojejunostomy approach, pancreatic texture, pancreatic duct diameter, and primary disease differed markedly between the two groups (p < .05). A multivariate analysis revealed that BMI ≥ 25 kg/m(2), internal pancreatic duct drainage, pancreatic duct diameter <3 mm, soft pancreatic texture, and ampullary disease were independent risk factors for PF. CONCLUSIONS: External pancreatic duct drainage can effectively reduce the morbidity of PF and overall complications after PD.

Necroptosis: a potential, promising target and switch in acute pancreatitis.

Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.