Blood and necrosectomy cultures were analysed to identify pathogens, antibiotic sensitivity and resistance patterns as well as pre-operative white cell count (WCC) and C-reactive protein (CRP).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Conclusion: The aneuploidy displayed by chromosomes 1, 6, 9 and 18 in pancreatic intraepithelial neoplasia appears to be related to chromosomal instability generated by abnormal expression of the ...mitotic checkpoint proteins Mad2 and BubR1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Background
Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease ...showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP.
Methods/design
DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (
α
), 80% power (1-
β
), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively.
Discussion
The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.
Trial registration
ISRCTN registry
ISRCTN44897265
. Prospectively registered on 16 April 2018.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To compare the procedural outcomes of minimally invasive and open central pancreatectomy. A systematic review in compliance with PRISMA statement standards was conducted to identify and analyze ...studies comparing the procedural outcomes of minimally invasive (laparoscopic or robotic) central pancreatectomy with the open approach. Random effects modeling using intention to treat data, and individual patient as unit of analysis, was used for analyses. Seven comparative studies including 289 patients were included. The two groups were comparable in terms of baseline characteristics. The minimally invasive approach was associated with less intraoperative blood loss (mean difference MD: -153.13 mL, p = 0.0004); however, this did not translate into less need for blood transfusion (odds ratio OR: 0.30, p = 0.06). The minimally invasive approach resulted in less grade B-C postoperative pancreatic fistula (OR: 0.54, p = 0.03); this did not remain consistent through sensitivity analyses. There was no difference between the two approaches in operative time (MD: 60.17 minutes, p = 0.31), Clavien-Dindo ≥ 3 complications (OR: 1.11, p = 0.78), postoperative mortality (risk difference: -0.00, p = 0.81), and length of stay in hospital (MD: -3.77 days, p = 0.08). Minimally invasive central pancreatectomy may be as safe as the open approach; however, whether it confers advantage over the open approach remains the subject of debate. Type 2 error is a possibility, hence adequately powered studies are required for definite conclusions; future studies may use our data for power analysis.To compare the procedural outcomes of minimally invasive and open central pancreatectomy. A systematic review in compliance with PRISMA statement standards was conducted to identify and analyze studies comparing the procedural outcomes of minimally invasive (laparoscopic or robotic) central pancreatectomy with the open approach. Random effects modeling using intention to treat data, and individual patient as unit of analysis, was used for analyses. Seven comparative studies including 289 patients were included. The two groups were comparable in terms of baseline characteristics. The minimally invasive approach was associated with less intraoperative blood loss (mean difference MD: -153.13 mL, p = 0.0004); however, this did not translate into less need for blood transfusion (odds ratio OR: 0.30, p = 0.06). The minimally invasive approach resulted in less grade B-C postoperative pancreatic fistula (OR: 0.54, p = 0.03); this did not remain consistent through sensitivity analyses. There was no difference between the two approaches in operative time (MD: 60.17 minutes, p = 0.31), Clavien-Dindo ≥ 3 complications (OR: 1.11, p = 0.78), postoperative mortality (risk difference: -0.00, p = 0.81), and length of stay in hospital (MD: -3.77 days, p = 0.08). Minimally invasive central pancreatectomy may be as safe as the open approach; however, whether it confers advantage over the open approach remains the subject of debate. Type 2 error is a possibility, hence adequately powered studies are required for definite conclusions; future studies may use our data for power analysis.
Familial adenomatous polyposis affects around 2-10 per 100,000 population. Untreated, it inevitably leads to colon cancer. Prophylactic panproctocolectomy has led to improved survival. The resulting ...extension to follow-up has revealed that 70-100% of patients with familial adenomatous polyposis go on to develop duodenal polyposis and the lifetime risk of duodenal carcinoma in this group is up to 10%. Treatment for those not locally resectable requires pancreaticoduodenectomy. In recent years, pancreas-preserving total duodenectomy has emerged as a safe alternative to pancreaticoduodenectomy. Endoscopy has previously been safely performed in patients following pancreas-preserving total duodenectomy.
We report successful endoscopic ultrasound (EUS) assessment and trans-neoduodenal EUS-guided fine needle aspiration biopsy (EUS-FNA) of the pancreas and adjacent tissue in a 45-year-old man with familial adenomatous polyposis who has previously undergone pancreas-preserving total duodenectomy. EUS confirmed the mass was most likely to represent a metastasis in a local lymph node. EUS-FNA confirmed invasive malignancy. A Kausch-Whipple pancreaticoduodenectomy was performed successfully and post-operative recovery has been excellent.
The authors consider this to be the first report of successful EUS and EUS-FNA performed through the neoduodenum fashioned during pancreas-preserving total duodenectomy.
Evidence currently available suggests that in established, progressively growing solid tumours, tumour associated macrophages (TAMs) are reprogrammed to induce immune suppression of host defenses in ...situ, through release of specific cytokines, prostanoids and other humoral mediators. This disordered response, results in the inhibition of effective anti-cancer cell-mediated immune mechanisms. Concurrently, TAMs produce tumour growth promoting factors. The summation of this complex interplay of biological factors results in progressive tumour growth and tumour cell dissemination. A better understanding of these complex inter-relationships should form the basis of novel strategies designed to eradicate tumour cells in man and animals. These various biological aspects and processes are discussed in detail and critically evaluated in this review article.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections ...including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 0.84–1.29, p = 0.711 and HR 1.18 0.95–1.46, p = 0.13 respectively) or OS (HR 0.96 0.79–1.17, p = 0.67 and HR 1.48 1.16–1.88, p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 1.02–1.74, p = 0.037) and OS (HR 1.26 1.03–1.53, p = 0.022). Furthermore, EBDR (OR 2.86 2.3–3.52, p < 0.0010), resection of additional organs (OR 2.22 1.62–3.02, p < 0.0010) and major hepatectomy (OR 3.81 2.55–5.73, p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 1.02–1.37, p = 0.031) but not OS (HR 1.05 0.91–1.22, p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP