OBJECTIVESGuidelines advocate minimally invasive drainage rather than open surgery for infected pancreatic necrosis (IPN) after acute pancreatitis. We hypothesized that the conservative approach ...could be extended even further by treating patients using an antibiotics-only protocol.
PATIENTS AND METHODSBetween June 2009 and July 2017, patients with IPN were selectively managed with carbapenem antibiotics for a minimum of 6 weeks. We compared these patients with patients who underwent minimal access retroperitoneal pancreatic necrosectomy (MARPN) for IPN to identify characteristics of this patient group.
RESULTSOf 33 patients with radiologically proven IPN, 13 patients received antibiotics without any surgical or radiological intervention and resulted in no disease-specific mortality and one case of pancreatic insufficiency. In comparison, 44 patients underwent MARPN with a mortality of 20%, and 81.8% developed pancreatic insufficiency. The modified Glasgow score and computed tomography severity score was less in the antibiotic-only group (P<0.001 and P=0.014, respectively). Patients who underwent MARPN had lower serum haemoglobin and albumin levels (P=0.030 and 0.001, respectively), and a higher C-reactive protein (P=0.027).
CONCLUSIONConservative treatment of IPN with antibiotics is a valid management option for haemodynamically stable patients experiencing less severe disease, requiring careful selection by experienced clinicians.
Background
Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ...ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior.
Methods
This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC.
Results
Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%,
P
< 0.001), dCCA (26.4%,
P
= 0.020), and finally PDAC (12.9%,
P
< 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size.
Conclusions
Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for “periampullary cancers” or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal ...pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data. OBJECTIVE: To evaluate the length of pooled learning curves of MIDP in experienced centers. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022. EXPOSURES: The learning curve for MIDP was estimated by pooling data from all centers. MAIN OUTCOMES AND MEASURES: The learning curve was assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix–expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C. RESULTS: From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean SD patient age, 58 15.3 years; among 2040 with reported sex, 1249 were female 61.2% and 791 male 38.8%). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at 70%. The learning-associated loss of TBO rate was estimated at 3.3%. For conversion, a break point was estimated at 40 procedures (95% CI, 11-68 procedures); for operation time, at 56 procedures (95% CI, 35-77 procedures); and for intraoperative blood loss, at 71 procedures (95% CI, 28-114 procedures). For postoperative pancreatic fistula, no break point could be estimated. CONCLUSION AND RELEVANCE: In experienced international centers, the learning curve length of MIDP for TBO was considerable with 85 procedures. These findings suggest that although learning curves for conversion, operation time, and intraoperative blood loss are completed earlier, extensive experience may be needed to master the learning curve of MIDP.
Objectives: The objective of this study was to compare short-term outcomes of pancreatoduodenectomy between patients with and without liver cirrhosis (LC). Background: It is not uncommon to encounter ...a patient with LC and with an indication for pancreatoduodenectomy; however, the knowledge on the outcomes after pancreatoduodenectomy in patients with LC is poorly developed. Methods: A systematic review and meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards. Short-term outcomes of pancreatoduodenectomy between patients with and without LC were compared using random effects modeling and the certainty of the evidence was assessed using the GRADE system. Results: Analysis of 18,184 patients from 11 studies suggested LC increased the risk of postoperative mortality (odds ratio OR: 3.94, P < 0.00001), major complications (OR: 2.25, P = 0.0002), and pancreatic fistula (OR: 1.73, P = 0.03); it resulted in more blood loss (mean difference MD: 204.74 ml, P = 0.0003) and longer hospital stay (MD: 2.05 days, P < 0.00001). LC did not affect delayed gastric emptying (OR: 1.33, P = 0.21), postoperative bleeding (OR: 1.28, P = 0.42), and operative time (MD: 3.47 minutes, P = 0.51). Among the patients with LC, Child-Pugh B or C class increased blood loss (MD: 293.33 ml, P < 0.00001), and portal hypertension increased postoperative mortality (OR: 2.41, P = 0.01); the other outcomes were not affected. Conclusions: Robust evidence with high certainty suggests LC of any severity with or without portal hypertension results in at least a fourfold increase in mortality and a twofold increase in morbidity after pancreatoduodenectomy. Whether such risks increase with the severity of the liver disease or decrease with optimization of underlying liver disease should be the focus of future research.
Aims: A bibliometric analysis identifies the major publications that influence the clinical management of Hepatocellular Carcinoma (HCC). Within this study, the 100 most cited HCC articles are noted ...and analysed.
Methods: The search terminology “Hepatocellular carcinoma” and “HCC” were used to search through the Thomson Reuters Web of Science database. The inclusion criteria consisted of English language full articles. The subject matter, author and institution details, year of publication and journal were recorded for the 100 most cited HCC articles. Citation rate index was calculated by dividing the number of citations by the number of years since publication.
Results: The search through the Thomson Reuters Web of Science database identified 39,518 eligible papers. The median (range) citation number was 909 (4419 to 458). The most cited article (produced by Llovet et al) discussed the role of Sorafenib in advanced HCC (4419 citations). Hepatology published the most articles (n=20, 20,533 citations), however the Lancet had the overall highest citation number of 39219, across 9 published articles. The most discussed topic was HCC management (n=31), followed by prognosis (n=18) and aetiology (n=15).
Conclusion: This bibliometric analysis has identified the 100 most cited HCC articles. Through integrating new knowledge into clinical practice, this has enabled novel treatment strategies to be utilised for patients with HCC. This study highlights what makes a citable article and may aid in the development for future HCC research themes.
Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform ...surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA.
Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence.
In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion.
Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell ...functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation.
Pseudoaneurysms in the celiac territory are mostly managed conservatively. Endovascular thromboembolisation with or without stenting is currently the standard treatment with good outcome. We present ...a case of a patient with chronic pancreatitis who initially underwent endovascular treatment for presumed splenic artery pseudoaneurysm and subsequently required surgical intervention for complicated unnamed artery pseudoaneurysm. Radiological diagnosis was instrumental in guiding the ensuing surgical procedure and the patient made a good postoperative recovery.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Kidins220 (Kinase D-Interacting Substrate, 220kDa), also known as ARMS (ankyrin repeat-rich membrane spanning) is a transmembrane scaffolding protein. Kidins220 acts as a platform for ...protein-protein interactions to coordinate cell plasticity, migration and neural growth receptor signalling. Present study aims to investigate the involvement of Kidins220 in the disease progression of pancreatic cancer. Pancreatic tumors (n=149) together with paired adjacent background tissues were collected at Peking University Cancer Hospital with written consent from the patients and also an ethical approval from the Peking University Cancer Hospital Research Ethics Committee. Kidins220 transcript levels were determined using real-time PCR. Relevance of Kidins220 transcript levels and pathologic/clinical features was analyzed. Knockdown of Kidins220 was carried out with a lentiviral Kidins220 shRNA. Immunohistochemical (IHC) staining of Kidins220 was performed on a pancreatic tissue microarray (TMA) (PA2081a, US Biomax, Inc., Rockville, MD, USA). A decreased expression of Kidins220 transcripts was observed in pancreatic cancer tissues in comparison with the paired background control (P=0.029). According to the TNM staging, early stage tumors (TNM 1&2) expressed higher levels of Kidins220 transcripts compared with its expression in more advanced tumors (TNM 3&4 stage, p=0.0034). In line with the finding from the Beijing pancreatic cancer cohort, a reduced expression of Kidins220 protein was seen in the pancreatic carcinomas of the TMA using IHC, p<0.001 compared with normal control. Moreover, based on the IHC results, primary tumors with distance metastases exhibited a decreased level of Kidins220 expression compared to those without metastasis. Knockdown of Kidins220 in pancreatic cancer cell lines PANC1 and MIA-PaCa-2 promoted migration and invasion of both cell lines. A protein array analysis (KinexTM) revealed an increased EGFR phosphorylation in the Kidins220 knockdown pancreatic cancer cell lines which was confirmed with Western blot. The Kidins220 knockdown-resulted increased invasion was eliminated by targeting EGFR using both gefitinib or with the irreversible pan-HER tyrosine kinase inhibitor, neratinib. Proliferation assays showed that neratinib was more effective to inhibit proliferation of PANC-1 and Mia-PaCa-2 cells at a range of concentration from 20nM to 2μM. In conclusion, the expression of Kidins220 was reduced in pancreatic cancer and the reduced expression in primary tumors was associated with distant metastases. Reduced Kidins220 expression promoted migration and invasion of pancreatic cancer cells through an upregulation of EGFR. The therapeutic potential of neratinib or gefitinib for reduced kidins220 relevant disease progression and metastasis in pancreatic cancers is yet to fully investigated.
Citation Format: Shuo Cai, Ping-Hui Sun, Xiangyu Gao, Ke Ji, Xiuyun Tian, Chunyi Hao, Bilal Al-Sarireh, Paul Griffiths, Steven Hiscox, Jared Tonkington, Jun Cai, Wen G. Jiang, Lin Ye. Reduced kinase D-interacting substrate of 220kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signaling and disease progression abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 89.
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