Artemether-Lumefantrine Treatment Failure despite adequate lumefantrine day 7 Concentration in a Traveller with Plasmodium Falciparum Malaria after Returning from Tanzania.

Artemether-lumefantrine is currently first-line therapy of Plasmodium falciparum malaria in many countries. This report describes a treatment failure despite adequate drug concentrations in a traveller returning from sub-Saharan Africa. Genotyping confirmed recrudescence and suggested reduced sensitivity. Potential sub-optimal effect of artemether-lumefantrine highlights the need to follow non-immune individuals the weeks after treatment

Liver regeneration and function following portal vein occlusion and hepatectomy

Background: Portal vein occlusion (PVO) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are two strategies employed to render patients with unresectable liver tumours resectable by increasing the size of the future liver remnant (FLR). There is still limited knowledge about several aspects of PVO and most aspects of ALPPS. Aims: To evaluate tumour progression after portal vein embolization (PVE) in patients with colorectal liver metastases (CRLM) treated with pre-procedural chemotherapy. To investigate if ALPPS performed after failed PVO in patients with CRLM treated with neoadjuvant chemotherapy is safe and feasible. To assess and compare liver volume and function in patients subjected to ALPPS. To study the levels of liver regenerative growth factors in ALPPS. Methods: In paper I, patients with CRLM and response to neoadjuvant chemotherapy, subjected to PVE at Skåne University Hospital (2005-2013) and Karolinska University Hospital (2004-2010) were included in the study and assessed for tumour progression. In paper II, patients subjected to ALPPS after failed PVO at Karolinska University Hospital were included and efficacy and safety of the procedure in these patients was evaluated. In paper III, the liver volume and function in patients subjected to ALPPS was studied with a multimodal approach (including repeated computed tomography and hepatobiliary scintigraphy). In paper IV, sequentially sampled tissue from patients operated with ALPPS was analysed to assess the levels of liver regenerative growth factors. Results: In paper I, 34 patients were identified and included. The median time between ended chemotherapy and PVE was 16 days. Three patients had tumour progression in the embolized liver lobe and three in the non-embolized lobe. Only two patients experienced tumour progression in the FLR that inhibited curative resection. In paper II, eleven patients operated with ALPPS after failed PVO were included. Six days after stage 1 the median growth of the FLR was 61.8% and all patients could proceed to stage 2 and resection of the liver tumours on day 7, with low morbidity and no 90-day mortality. In paper III, nine patients were studied and the increase in FLR-volume exceeded the increase in FLR-function at day 6 after stage 1, where functional increase only reached 50% of the volume increase in the FLR. In paper IV, ten patients were studied. The levels of HGF in plasma correlated with the degree of growth of the FLR and the levels of IL-6 correlated with the HGF levels. Conclusions: The rate of progression of CRLM after PVE with pre-procedural chemotherapy is lower than previously reported if the time between the end of chemotherapy and PVE is short. The powerful growth of the FLR associated with ALPPS seems to be maintained in patients with CRLM treated with neoadjuvant chemotherapy and previously failed PVO. In the interstage period of ALPPS the high volume increase is not paralleled by a corresponding functional increase. The levels of HGF in plasma correlates with the degree of growth of the FLR and the levels of IL-6 correlates with the HGF levels in patients operated with ALPPS

Development and external validation of DISPAIR fistula risk score for clinically relevant postoperative pancreatic fistula risk after distal pancreatectomy

This study describes the development and external validation of the DISPAIR score, a preoperative clinical prediction model to estimate the risk of postoperative pancreatic fistula after distal pancreatectomy. It is based on three variables measured before operation: pancreatic thickness, transection site, and history of diabetes. On external validation, it showed satisfactory discrimination (area under the curve 0.80) and calibration (slope 0.719, intercept 0.192) for predicting pancreatic fistula. Background Highly utilized risk scores for clinically relevant postoperative pancreatic fistula (CR-POPF) have guided clinical decision-making in pancreatoduodenectomy. However, none has been successfully developed for distal pancreatectomy. This study aimed to develop and validate a new fistula risk score for distal pancreatectomy. Methods Patients undergoing distal pancreatectomy at Helsinki University Hospital, Finland from 2013 to 2021, and at Karolinska University Hospital, Sweden, from 2010 to 2020, were included retrospectively. The outcome was CR-POPF, according to the 2016 International Study Group of Pancreatic Surgery definition. Preoperative clinical demographics and radiological parameters such as pancreatic thickness and duct diameter were measured. A logistic regression model was developed, internally validated with bootstrapping, and the performance assessed in an external validation cohort. Results Of 668 patients from Helsinki (266) and Stockholm (402), 173 (25.9 per cent) developed CR-POPF. The final model consisted of three variables assessed before surgery: transection site (neck versus body/tail), pancreatic thickness at transection site, and diabetes. The model had an area under the receiver operating characteristic curve (AUROC) of 0.904 (95 per cent c.i. 0.855 to 0.949) after internal validation, and 0.798 (0.748 to 0.848) after external validation. The calibration slope and intercept on external validation were 0.719 and 0.192 respectively. Four risk groups were defined in the validation cohort for clinical applicability: low (below 5 per cent), moderate (at least 5 but below 30 per cent), high (at least 30 but below 75 per cent), and extreme (75 per cent or more). The incidences in these groups were 8.7 per cent (11 of 126), 22.0 per cent (36 of 164), 63 per cent (57 of 91), and 81 per cent (17 of 21) respectively. Conclusion The DISPAIR score after distal pancreatectomy may guide decision-making and allow a risk-adjusted outcome comparison for CR-POPF.Peer reviewe

Secondary effects of the COVID-19 pandemic on surgical management of hepatopancreatobiliary malignancies in the Nordic capitals

Non peer reviewe

Liver transplantation in patients with post-hepatectomy liver failure - A Northern European multicenter cohort study

Background: Liver transplantation (LTX) has been described as a rescue treatment option in severe, intractable post-hepatectomy liver failure (PHLF), but is not considered to be indicated for this condition by many hepatobiliary and transplant surgeons. In this article we describe the clinical experience of five northern European tertiary centers in using LTX to treat selected patients with severe PHLF. Methods: All patients subjected to LTX due to PHLF at the participating centers were identified from prospective clinical databases. Preoperative variables, surgical outcome (both resection surgery and LTX) and follow-up data were assessed.Results: A total of 10 patients treated with LTX due to severe PHLF from September 2008 to May 2020 were identified and included in the study. All patients but one were male and the median age was 70 years (range 49-72). In all patients the indication for liver resection was suspected malignancy, but in six patients post-resection pathology revealed benign or pre-malignant disease. There was no 90-day mortality after LTX. Patients were followed for a median of 49 months (13-153) and eight patients were alive without recurrence at last follow-up.Discussion: In selected patients with PHLF LTX can be a life-saving procedure with low short-term risk.Peer reviewe

Surgery for Bismuth-Corlette Type 4 Perihilar Cholangiocarcinoma:Results from a Western Multicenter Collaborative Group

Contains fulltext : 239075.pdf (Publisher’s version ) (Open Access)BACKGROUND: Although Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database. METHODS: Uni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA. RESULTS: Among 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60). CONCLUSIONS: In this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required

Preoperative immunological plasma markers TRAIL, CSF1 and TIE2 predict survival after resection for biliary tract cancer

IntroductionSystemic inflammatory markers have been validated as prognostic factors for patients with biliary tract cancer (BTC). The aim of this study was to evaluate specific immunologic prognostic markers and immune responses by analyzing preoperative plasma samples from a large prospectively collected biobank.MethodsExpression of 92 proteins representing adaptive and innate immune responses was investigated in plasma from 102 patients undergoing resection for BTC 2009-2017 (perihilar cholangiocarcinoma n=46, intrahepatic cholangiocarcinoma n=27, gallbladder cancer n=29), by means of a high-throughput multiplexed immunoassay. Association with overall survival was analyzed by Cox regression, with internal validation and calibration. Tumor tissue bulk and single-cell gene expression of identified markers and receptors/ligands was analyzed in external cohorts.ResultsThree preoperative plasma markers were independently associated with survival: TRAIL, TIE2 and CSF1, with hazard ratios (95% confidence intervals) 0.30 (0.16-0.56), 2.78 (1.20-6.48) and 4.02 (1.40-11.59) respectively. The discrimination of a preoperative prognostic model with the three plasma markers was assessed with concordance-index 0.70, while the concordance-index of a postoperative model with histopathological staging was 0.66. Accounting for subgroup differences, prognostic factors were assessed for each type of BTC. TRAIL and CSF1 were prognostic factors in intrahepatic cholangiocarcinoma. In independent cohorts, TRAIL-receptor expression was higher in tumor tissue and seen in malignant cells, with TRAIL and CSF1 expressed by intra- and peritumoral immune cells. Intratumoral TRAIL-activity was decreased compared to peritumoral immune cells, while CSF1-activity was increased. The highest CSF1 activity was seen in intratumoral macrophages, while the highest TRAIL-activity was seen in peritumoral T-cells.DiscussionIn conclusion, three preoperative immunological plasma markers were prognostic for survival after surgery for BTC, providing good discrimination, even compared to postoperative pathology. TRAIL and CSF1, prognostic factors in intrahepatic cholangiocarcinoma, showed marked differences in expression and activity between intra- and peritumoral immune cells

Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection - A DRAGON collaborative analysis of 306 patients

Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p &lt; 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR ≥2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.</p

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review

Background: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. Methods: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010–2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. Results: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). Conclusion: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers

Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15–18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12–14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.publishedVersio