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Duodenoscope-related multidrug-resistant organism (MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography (ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score (1 to 10) on performance rating of the single-use duodenoscope, and adverse event (AE) rate. A total of 66 patients (26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47 (71.2%) grade 3 and 19 (28.8%) grade 4. The technical success rate was 98.5% (65/66). Procedural duration was 64 (interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66 (1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients (6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis (PEP), 1 cholangitis and 1 bleeding. Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.
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Postoperative pancreatic fistula is the main cause of morbidity after pancreatic resection. This study aimed to quantify the clinical and economic consequences of pancreatic fistula in a medium-volume pancreatic surgery center. Hospital records from patients who had undergone elective pancreatic resection in our department were identified. Pancreatic fistula was defined according to the International Study Group on Pancreatic Fistula (ISGPF). The consequences of pancreatic fistula were determined by treatment cost, hospital stay, and out-patient follow-up until the pancreatic fistula was completely healed. All costs of the treatment are calculated in Euros. The cost increase index was calculated for pancreatic fistula of grades A, B, and C as multiples of the total cost for the no fistula group. In 54 months, 102 patients underwent elective pancreatic resections. Forty patients (39.2%) developed pancreatic fistula, and 54 patients (52.9%) had one or more complications. The median length of hospital stay for the no fistula, grades A, B, and C fistula groups was 12.5, 14, 20, and 59 days, respectively. The hospital stay of patients with fistula of grades B and C was significantly longer than that of patients with no fistula (P<0.001). The median total cost of the treatment was 4952, 4679, 8239, and 30 820 Euros in the no fistula, grades A, B, and C fistula groups, respectively. The grading recommended by the ISGPF is useful for comparing the clinical severity of fistula and for analyzing the clinical and economic consequences of pancreatic fistula. Pancreatic fistula prolongs the hospital stay and increases the cost of treatment in proportion to the severity of the fistula.
Early diagnosis of postoperative pancreatic fistula (POPF) is important for proper interventions. The preoperative, intraoperative and early postoperative biochemical markers have predictive value of POPF. The present study was to evaluate several simple biochemical parameters in the prediction of POPF. Patients who underwent pancreaticoduodenectomy in our center between 2006 and 2015 were reviewed retrospectively. Preoperative and early postoperative biochemical parameters were evaluated. Additionally, the relationship between POPF and pH and lactate level at the end of surgery were analyzed, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red cell distribution width-to-platelet ratio (RPR) were calculated for postoperative days (PODs) 1 and 3. Diagnosis and grading of POPF were performed according to the standards of the International Study Group on Pancreatic Fistula. The patients were divided into two groups: Group 1 with no fistula or grade-A fistula; group 2 with grade-B or -C fistula. These simple biochemical markers were then compared between the two groups. Serum amylase level was significantly higher at POD3, and pH level was significantly lower at the end of operation in group 2 compared with those in group 1. However, the serum amylase was below the upper limit of normal serum level and therefore, the difference was not significant in clinical practice. Receiver operating charecteristic curve analysis showed that pH level was a reliable predictor of POPF (area under the curve: 0.713; 95% CI: 0.573-0.853). A low pH level at the end of pancreaticoduodenectomy was a risk factor of POPF. NLR, PLR, and RPR had no predictive value of POPF after pancreaticoduodenectomy.
Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions (PCLs) by analyzing large epidemiologic data. Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea. The final number of patients with pancreatic cysts was 165 277 among the total claims for reimbursement of 855 983 associated with PCLs over 12 years. The total number of claims were increased from 19 453 in 2007 to 155 842 in 2018 and the prevalence increased from 0.04% to 0.23%. For 12 years, 2874 (1.7%) had pancreatic cancer and 8212 (5.0%) underwent surgery, and 36 had surgery for twice (total 8248 pancreatectomy). After ruling out claims from the first 3 years of washout period, the incidence increased from 9891 to 24 651 and the crude incidence rate of PCLs expanded from 19.96 per 100 000 to 47.77 per 100 000. Compared to specific neoplasm codes (D136 or D377), the use of pancreatic cyst code (K862) has been remarkably increased and the most common since 2010. The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012, and decreased to 596 until 2018. The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6% in 2007 to 11.7% in 2018. The incidence of PCLs is rapidly increasing. Among PCLs, indeterminate cyst is increasing outstandingly. A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.
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Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis with a discrete pathophysiology, occasional diagnostic radiological findings, and characteristic histological features. Its etiology and pathogenesis are still under investigation, especially during the last decade. Another aspect of interest is the attempt to establish specific criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer, entities that are frequently indistinguishable. An extensive search of the PubMed database was performed with emphasis on articles about the differential diagnosis between autoimmune pancreatitis and pancreatic cancer up to the present. The most interesting outcome of recent research is the theory that autoimmune pancreatitis and its various extra-pancreatic manifestations represent a systemic fibro-inflammatory process called IgG4-related systemic disease. The diagnostic criteria proposed by the Japanese Pancreatic Society, the more expanded HISORt criteria, the new definitions of histological types, and the new guidelines of the International Association of Pancreatology help to establish the diagnosis of the disease types. The valuable help of the proposed criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer may lead to avoidance of pointless surgical treatments and increased patient morbidity.
Neural invasion is a special metastatic route in pancreatic cancer and responsible for the high recurrence in curatively resected cases. To summarize the characteristics and mechanisms of neural invasion in pancreatic carcinoma for the better treatment of this disease. The international literatures were reviewed about the definition, incidence and mechanisms of neural invasion and its clinicopathology, diagnosis and treatment. Neural invasion is defined when the medial perineurium is involved by cancer cells, accounting for 45%-100% of all cases. It can be divided into different kinds or stages according to its locations and the number of nerve fascicles involved. Invasion along vascularity, lymphatic vessels, perineural space and neurotropism is considered as its primary mechanisms. No clinicopathologic factors are correlated with neural invasion. Intravascular ultrasound, CT scan and immunostaining K-ras gene analysis can be used to diagnose neural invasion pre-, intra- or postoperatively. Neural invasion is an important prognostic factor for the recurrence of pancreatic carcinoma after pancreatectomy. Because of its high incidence, pancreatectomy with extended radical retroperitoneal dissection should be considered as a basic procedure in the treatment of pancreatic carcinoma.
Postoperative pancreatic fistula is one of the most common complications after pancreatectomy. This study aimed to assess the occurrence and severity of pancreatic fistula after central pancreatectomy. The medical records of 13 patients who had undergone central pancreatectomy were retrospectively studied, together with a literature review of studies including at least five cases of central pancreatectomy. Pancreatic fistula was defined and graded according to the recommendations of the International Study Group on Pancreatic Fistula (ISGPF). No death was observed in the 13 patients. Pancreatic fistula developed in 7 patients and was successfully treated non-operatively. None of these patients required re-operation. A total of 40 studies involving 867 patients who underwent central pancreatectomy were reviewed. The overall pancreatic fistula rate of the patients was 33.4% (0-100%). Of 279 patients, 250 (89.6%) had grade A or B fistulae of ISGPF and were treated non-operatively, and the remaining 29 (10.4%) had grade C fistulae of ISGPF. In 194 patients, 15 (7.7%) were re-operated upon. Only one patient with grade C fistula of ISGPF died from multiple organ failure after re-operation. Despite the relatively high occurrence, most pancreatic fistulae after central pancreatectomy are recognized a grade A or B fistula of ISGPF, which can be treated conservatively or by mini-invasive approaches.
Pancreatic fistula (PF) remains the most challenging complication in pancreatic surgery, yet few published studies have focused on the risk factors for postoperative PF in patients undergoing surgery for insulinomas. From January 1990 to February 2010, a total of 292 patients with insulinomas underwent surgery at Peking Union Medical College Hospital. Demographic data, intraoperative procedures, and postoperative data were collected. Particular attention was paid to variables associated with PF as defined by the International Study Group of Pancreatic Fistula (ISGPF). Univariate and multivariate analyses were used to identify possible risk factors for PF. PF was found in 132 (45.2%) patients, of whom 90 were classified into ISGPF grade A, 33 grade B, and 9 grade C. Multivariate analysis showed that male patients (OR=2.56; P=0.007) and operative time >180 minutes (OR=3.756; P<0.0001) were independent risk factors for clinical PF. Pancreatic resection with stapler was a protective factor for both total PF (OR=0.022; P=0.010) and clinical PF (OR=0.097; P=0.007). Male gender and operative time >180 minutes were independent risk factors for clinical PF, while pancreatic resection with a stapler was a protective factor. Whether body mass index (BMI) and other variables during operation are risk factors of PF needs further study.
Soft pancreatic texture and a small main pancreatic duct are thought to be the most significant risk factors for the occurrence of pancreatic fistula (PF), a common and serious complication after pancreaticoduodenectomy (PD). This is in part due to the technical difficulties of pancreaticojejunostomy (PJ) posed by a soft gland with a normal-sized duct. To deal with this problem, we developed a new anastomotic technique which combines the two most widely used techniques, namely, the invagination technique and the duct-to-mucosa technique, with a modification of the suture route and insertion of a temporary stent tube. Between January 2003 and December 2009, ninety-two consecutive patients underwent PD in which the new PJ technique was used. Charts and follow-up data of these patients were reviewed for operative details, early postoperative events, and outcomes at 6 months after the operation. PF was defined by the International Study Group on Pancreatic Fistula (ISGPF) guidelines and graded (A, B or C) according to the clinical procedures and outcome. In this group of 92 patients, there was only 1 early death from acute renal failure. PF was observed in 11 patients (12.0%), 8 in grade A, 1 in grade B, and 2 in grade C. For the 2 patients in grade C, PF was surgically managed. There were no early or late deaths attributable to PF. Six months after the operation, all of the patients were free of PJ-related symptoms except for 2, who were found to have steatorrhea. Our modified technique is simple and safe in PD. Present data suggest that this technique produces excellent early and medium-term results.
Recent international multidisciplinary consultation proposed the use of local (sterile or infected pancreatic necrosis) and/or systemic determinants (organ failure) in the stratification of acute pancreatitis. The present study was to validate the moderate severity category by international multidisciplinary consultation definitions. Ninety-two consecutive patients with severe acute pancreatitis (according to the 1992 Atlanta classification) were classified into (i) moderate acute pancreatitis group with the presence of sterile (peri-) pancreatic necrosis and/or transient organ failure; and (ii) severe/critical acute pancreatitis group with the presence of sterile or infected pancreatic necrosis and/or persistent organ failure. Demographic and clinical outcomes were compared between the two groups. Compared with the severe/critical group (n=59), the moderate group (n=33) had lower clinical and computerized tomographic scores (both P<0.05). They also had a lower incidence of pancreatic necrosis (45.5% vs 71.2%, P=0.015), infection (9.1% vs 37.3%, P=0.004), ICU admission (0% vs 27.1%, P=0.001), and shorter hospital stay (15+/-5 vs 27+/-12 days; P<0.001). A subgroup analysis showed that the moderate group also had significantly lower ICU admission rates, shorter hospital stay and lower rate of infection compared with the severe group (n=51). No patients died in the moderate group but 7 patients died in the severe/critical group (4 for severe group). Our data suggest that the definition of moderate acute pancreatitis, as suggested by the international multidisciplinary consultation as sterile (peri-) pancreatic necrosis and/or transient organ failure, is an accurate category of acute pancreatitis.
Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common and severe complication after pancreaticoduodenectomy (PD). Despite the development of numerous anastomotic surgical techniques to minimize CR-POPF, more than 30% of patients who undergo PD develop CR-POPF. Herein, we propose a novel pancreaticojejunostomy (PJ) technique and evaluate its efficacy and safety compared to traditional PJ. This retrospective study enrolled 164 consecutive patients who underwent PJ after PD between January 2012 and June 2017. Of them, 78 (47.6%) underwent traditional PJ and 86 (52.4%) underwent six-stitch PJ. The primary outcome was CR-POPF at 1-month follow-up defined according to the revised 2016 International Study Group on Pancreatic Fistula definition. To adjust for baseline differences and selection bias, patients were matched by propensity scores, which left 63 patients with traditional PJ and 63 with six-stitch PJ. Compared to patients who underwent traditional PJ (mean age 56.2 ± 9.4 years), patients who underwent six-stitch PJ (mean age 57.4 ± 11.4 years) had a lower CR-POPF rate. The risk of CR-POPF among patients who underwent six-stitch PJ was decreased by 81.7% after adjustment for age, sex, body mass index, and disease severity compared to patients who underwent traditional PJ. Additionally, the surgery time was reduced from 29 min for traditional PJ to 15 min for six-stitch PJ (P <0.001). Adverse effects such as abdominal fluid collection, abdominal bleeding, and wound infection were similar between two groups. Six-stitch PJ may be an effective and efficient PJ technique for patients who undergo PD surgery.
Tumor micronecrosis is a feature of hepatocellular carcinoma (HCC) and might mirror tumor characteristics and patient prognosis. However, the specific influence of tumor micronecrosis on the recurrence patterns of HCC remains unclear. This study aimed to investigate the effects of tumor micronecrosis on HCC recurrence patterns, particularly examining any changes after liver resection. A cohort of 938 patients with primary HCC who underwent R0 liver resection between June 2014 and October 2019 were included in the study. A second R0 resection was performed in 340 patients with tumor recurrence between November 2014 and October 2021. Tumor micronecrosis was evaluated for primary (938 cases) and recurrent (340 cases) tumors. The recurrence pattern and prognosis were analyzed, and independent prognostic factors were identified using Cox regression analysis. Nomograms were then constructed to predict tumor recurrence and prognosis after liver resection. HCC recurrence was observed in 400 (42.6%) patients during the follow-up period. Tumor micronecrosis independently affected recurrence-free survival (P = 0.002). Among micronecrosis (+) patients, a higher extrahepatic recurrence, multiple tumors, elevated albumin-bilirubin grade, advanced Barcelona Clinic Liver Cancer stage, and increased alpha-fetoprotein level were observed. Additionally, more micronecrosis (-) patients underwent positive treatments after recurrence (P = 0.017), leading to a superior post-recurrence prognosis in this group (P < 0.001). Nearly half of the recurrent HCCs displayed changes in tumor micronecrosis scores. The presence of micronecrosis in primary lesions was significantly associated with poor patient survival after recurrence (P = 0.006), whereas no significant association was observed in patients with recurrent lesions after second R0 resection (P = 0.138). Furthermore, early recurrence, multinodular recurrence, intrahepatic and extrahepatic recurrent tumors, and the treatment modality were identified as independent prognostic factors. The developed nomogram for patient survival achieved a concordance index of 0.753. Patients with HCC displaying tumor micronecrosis experienced increased recurrent risks and more aggressive recurrent patterns, and encountered poorer prognosis compared to those without micronecrosis. Notably, micronecrosis status often varied between primary and recurrent HCCs. However, micronecrosis predicted survival only when evaluated in the primary tumor, not in the recurrent tumors.
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Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis (AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKKβ/NF-κB signaling and pro-inflammatory cytokine production. Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKKβ/NF-κB activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-α and IL-1β levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKKβ, and p-IKKβ were detected by Western blotting. In rat AP models, AP severity was correlated with increased IKKβ/NF-κB activation, pro-inflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-α and IL-1β as well as IKKβ/NF-κB signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. Serum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKKβ/NF-κB signaling pathway.
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