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BackgroundTotal pancreatectomy (TP) is rarely performed due to concerns for endocrine and exocrine insufficiency and decreased quality of life (QoL). Renewed interest is seen in recent years, but large cohort studies remain scarce. This study was designed to evaluate endocrine and exocrine insufficiency after TP and its impact on QoL.MethodsAdult patients (age ≥ 18 years) who underwent TP between 2008 and 2017 at Karolinska University Hospital with at least 6 months follow-up were included. Endocrine and exocrine insufficiency and QoL were assessed using validated questionnaires (EORTC QLQ-C30, QLQ-PAN26, PAID20, and DTSQs). Both pre- and postoperative questionnaires were available in a subgroup.ResultsOf 145 TP, 60 patients were eligible of whom 53 (88.3%) with a median of 21 months (interquartile range [IQR] 13–54) follow-up were included. Symptomatic hypoglycemia occurred in 90.6% (48/53) of patients, and 25% (12/48) experienced ≥ 1 episodes of loss of consciousness. The PAID20 revealed emotional burnout in seven patients (13.2%), whereas a high satisfaction score of diabetes treatment (median 28, IQR 24–32) was measured according to the DTSQs. Overall, 27 patients (50.9%) reported to have steatorrhea during a median of 2 days (IQR 0–4) in the past week. Overall QoL was reduced compared with a general population (66.7% vs. 76.4%; Δ9.7%) but did not differ with preoperative outcomes (n = 39, 66.7%; IQR 41.7–83.3 vs. 66.7%, IQR 50.0–83.3; P = 0.553) according to the EORTC QLQ-C30.ConclusionsAlthough the impact of endocrine and exocrine insufficiency on QoL after TP seems acceptable, the management of both insufficiencies should be further improved.

BackgroundThe impact of high-volume care in total pancreatectomy (TP) is barely explored since annual numbers are mostly low. This study evaluated surgical outcomes after TP over time in a high-volume center.MethodsAll adult patients (age ≥ 18 years) who underwent an elective single-stage TP at Karolinska University Hospital were retrospectively analysed (2008–2017). High volume was defined as > 20 TPs/year.ResultsOverall, 145 patients after TP were included, including 86 (59.3%) extended resections. Major morbidity was 34.5% (50/145) and 90-day mortality 5.5% (8/145). The relative use of TP within all pancreatectomies increased from 5.4% (63/1175) in 2008–2015 to 17.3% (82/473) in 2016–2017 (p < 0.001). Over time, TP was more often performed to achieve radicality (n = 11, 17.5% to n = 31, 37.8%; p = 0.007). In multivariable logistic regression analysis, an annual TP-volume of > 20 was associated with reduced major morbidity (odds ratio [OR] = 0.225, 95% confidence interval [CI], 0.097–0.521; p < 0.001). In the high-volume years (2016–2017), major morbidity (n = 31, 49.2% to n = 19, 23.2%; p = 0.001) and relaparotomy rate (n = 13, 20.6% to n = 5, 6.1%; p = 0.009) improved. Improvements occurred mainly after extended TP, including lower major morbidity (n = 22, 57.9% to n = 12, 25.0%; p = 0.002) and in-hospital mortality (n = 3, 7.9% to n = 0, 0%; p = 0.082).ConclusionsIn a single, high-volume center study, an increase in surgical volume of TP was associated with improved perioperative outcomes, especially for extended resections.

Background Post-pancreatectomy acute pancreatitis (PPAP) is a recently identified clinical condition characterized by sustained elevated serum amylase levels for at least 48 h post-operatively, consistent radiological findings, and relevant clinical features. The purpose of this study was to determine the frequency of PPAP after DP, to investigate the rate of major complications in patients with sustained or transiently elevated serum amylase activity, and to explore the usability of CT as a prerequisite for the diagnosis of PPAP. Methods This retrospective single-center observational study included consecutive patients 18 years or older who underwent DP at Karolinska University Hospital between 2008 and 2020. The two serum amylase levels on post-operative days (POD) 1 and 2 were correlated with post-operative major complications by logistic regression analyses. Results Of the 403 patients who underwent DP, 14% ( n  = 58) had sustained elevated serum amylase levels according to PPAP criteria, and 31% ( n  = 126) had transiently elevated serum amylase levels on either POD1 or POD2. Of the patients with sustained elevated levels, 45% ( n  = 26) developed major complications, but less than 2% ( n  = 1) showed imaging findings consistent with acute pancreatitis. Of the 126 patients who exhibited only transiently elevated serum amylase on either POD1 or POD2, 38% ( n  = 48) developed major complications. The frequency of PPAP was 0.25% ( n  = 1). Conclusion These findings indicate that PPAP after DP is rare and that computed tomography has limited usability for diagnosing PPAP. The findings also suggest that transiently elevated serum amylase may be an early indicator of acute pancreatitis, especially when peaked.

Pancreatic cancer is an aggressive disease with a dense fibrotic stroma and is often accompanied by chronic inflammation. Peritumoral inflammation is typically viewed as a reaction to nearby tumor growth. Here, we report that the inflamed pancreatic lobules are frequently invaded by tumor cells, forming a distinct, non-fibrotic tumor niche. Using a semi-supervised machine learning approach for annotations of clinical samples and multiplex protein profiling, we show that tumor cells at the invasion front are closely associated with acinar cells undergoing damage-induced changes, and with activated fibroblasts expressing markers of injury. The invaded lobules are linked to classical tumor phenotypes, in contrast to fibrotic areas where tumor cells display a more basal profile, highlighting microenvironment-dependent tumor subtype differences. In female mice, lobular invasion similarly aligns with the classical tumor phenotype. Together, our data reveal that pancreatic tumors colonize injured lobules, creating a unique niche that shapes tumor characteristics and contributes to disease biology. Peritumoural pancreatitis and lobular injury are commonly seen in pancreatic cancer. Here, the authors reveal interactions between invading tumour cells and inflammation-related lobular cells, linked to switching from a basal to classical tumor cell phenotype.

Background Clinically relevant (CR) postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) are common. Endoscopic treatment (ET) has only scarcely been explored. The aim of this study was to evaluate risk factors for CR POPF after DP and the efficacy of ET in adjunct to standard therapy. Methods Consecutive patients without previous pancreatic surgery who underwent DP between 2011 and 2020 were evaluated, analyzing risk factors for CR POPF. The choice and performance of ET, main pancreatic duct (MPD) stenting, was not standardized. Healing time and complications after ET were registered. Results 406 patients underwent DP, CR POPF occurred in 29.6%. ET was performed in 17 patients 27 days (median) after index surgery. Risk for CR POPF was increased in ASA-PS 1–2 patients, MPD  ≤  3 mm, procedure time  ≥  3 h, and CRP  ≥  180 on postoperative day 3. POPF resolved with standard treatment after 32 days and 59 days in the ET group (p < 0.001). There was one mortality in the ET-group (not procedure related). Mild post-ERCP pancreatitis occurred in three patients. Conclusions CR POPF is common after DP. Long operating time, a narrow MPD, low ASA score, and high postoperative CRP were risk factors for CR POPF. ET was not beneficial but proper evaluation was not possible due to few patients and non-standardized treatment. Complications after ET appeared mild.

Introduction Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. The majority of patients are diagnosed at an advanced stage, and for these patients, the only possible treatment is palliative chemotherapy. There are increasing data from retrospective studies indicating that a subgroup of patients with liver-limited metastases may benefit from surgical treatment of liver metastases. However, there is a need for prospective trials. Objective The aim of this study is to prospectively investigate the safety and feasibility of surgically treating patients who are resectable, including those with borderline venous resectable, histopathologically confirmed PDAC, and histopathologically or radiologically confirmed liver metastases. Methods Five Swedish and one Finnish hepatopancreaticobiliary (HPB) centre will participate. Eligible patients will be identified at regional multidisciplinary conferences (MDTs). Before inclusion, they will undergo computed tomography (CT), magnetic resonance imaging (MRI, ) and (positron emission tomography computed tomography)PET-CT to rule out extrahepatic metastases. To be included, patients will have to have four or fewer liver metastases, which must be no larger than 5 cm for patients planning for resection and no larger than 2 cm for patients planning for ablation. The metastases may be either synchronous or metachronous. Patients will undergo four months of chemotherapy before surgical treatment (either resection or ablation), and postoperatively, they will undergo two months of chemotherapy. For those with synchronous metastases, resection of the pancreatic tumour will be performed. Follow-up will be performed over two years postoperatively with regular CT scans and assessments of quality of life. Conclusions In conclusion, this trial will provide increased knowledge concerning whether surgical treatment of liver metastases from pancreatic cancer can result in improved survival. Clinical Trial Number Clinical.Trials.gov (NCT05271110), registered February 26 th 2022

Objectives: Autoimmune pancreatitis (AIP) type 1, paraduodenal (groove) pancreatitis, and follicular pancreatitis are rare clinical entities whose diagnosis may be challenging, given the potential imaging overlap with pancreatic cancer. Methods: We performed a retrospective analysis of the medical chart of a patient with multiple pancreas pathologies. Results: We present a case with multiple pancreas pathologies, including a poorly differentiated ductal adenocarcinoma of pancreatobiliary type, an intraductal papillary mucinous lesion (pre-existing lesion of IPMN type), and an inflammatory process with complex features, in which paraduodenal (groove) pancreatitis, follicular pancreatitis, and IgG4-related pancreatitis (AIP type 1) were also present. Conclusions: The diagnosis of AIP and paraduodenal pancreatitis is not always straightforward, and in some cases, it is not easy to differentiate them from pancreatic cancer. Surgery should be considered in patients when a suspicion of malignant/premalignant lesions cannot be excluded after a complete diagnostic work-up.

BackgroundGastric venous congestion (GVC) after total pancreatectomy (TP) is rarely studied despite its high 5% to 28% incidence and possible association with mortality. This study aimed to provide insight about incidence, risk factors, management, and outcome of GVC after TP.MethodsThis retrospective observational single-center study included all patients undergoing elective TP from 2008 to 2021. The exclusion criteria ruled out a history of gastric resection, concomitant (sub)total gastrectomy for oncologic indication(s) or celiac axis resection, and postoperative (sub)total gastrectomy for indication(s) other than GVC.ResultsThe study enrolled 268 patients. The in-hospital major morbidity (Clavien-Dindo grade ≥IIIa) rate was 28%, and the 90-day mortality rate was 3%. GVC was identified in 21% of patients, particularly occurring during index surgery (93%). Intraoperative GVC was managed with (sub)total gastrectomy for 55% of the patients. The major morbidity rate was higher for the patients with GVC (44% vs 24%; p = 0.003), whereas the 90-day mortality did not differ significantly (5% vs 3%; p = 0.406). The predictors for major morbidity were intraoperative GVC (odds ratio [OR], 2.207; 95% confidence interval [CI], 1.142–4.268) and high TP volume (> 20 TPs/year: OR, 0.360; 95% CI, 0.175–0.738). The predictors for GVC were portomesenteric venous resection (PVR) (OR, 2.103; 95% CI, 1.034–4.278) and left coronary vein ligation (OR, 11.858; 95% CI, 5.772–24.362).ConclusionsAfter TP, GVC is rather common (in 1 of 5 patients). GVC during index surgery is predictive for major morbidity, although not translating into higher mortality. Left coronary vein ligation and PVR are predictive for GVC, requiring vigilance during and after surgery, although gastric resection is not always necessary. More evidence on prevention, identification, classification, and management of GVC is needed.

Background Post-pancreatectomy acute pancreatitis (PPAP) is a newly described clinical entity defined as elevated serum amylase sustained ≥ 48 h postoperatively, radiological findings consistent with acute pancreatitis, and associated clinically relevant features. This study aimed to investigate the incidence of PPAP and the rate of major complications after pancreatoduodenectomy (PD) in patients with only transiently elevated serum amylase. Methods A retrospective single-center observational study was conducted including consecutive patients ≥ 18 years of age undergoing PD at Karolinska University Hospital, between 2008 and 2020. Serum amylase on postoperative day (POD) 1 and 2 and records from computer tomography were analyzed and correlated with postoperative major complications by logistic regressions. Results Of some 1078 patients that underwent PD, 284 exhibited sustained elevated serum amylase (according to PPAP criteria) and 183 transiently elevated serum amylase on either POD1 or POD2. Of the patients with sustained elevated levels, 43% ( n  = 123) developed major complications, but only 6.3% ( n  = 18) showed findings consistent with acute pancreatitis on imaging. Of the 183 cases that exhibited only transiently elevated serum amylase on either POD1 or POD2, 32% ( n  = 58) developed major complications. Conclusion Sustained hyperamylasemia was observed in 26% of patients after PD, and an additional 17% of patients had a transient elevation of serum amylase postoperatively. Acute pancreatitis after PD may be underdiagnosed, partly by overlooking transiently elevated serum amylase and partly by requiring imaging that potentially fails to recognize mild but complication-prone acute pancreatitis.