| 1. |
- D'Souza, Melroy Alistair
(författare)
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Hepatic ischemia-reperfusion injury
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hepatic ischemia-reperfusion (I/R) injury is a complex phenomenon occuring in response to interruption of the liver’s blood and oxygen supply and the subsequent restoration of blood flow and tissue oxygenation. Techniques to reduce blood loss and other intra-operative manoeuvers during liver resection can cause hepatic I/R injury. I/R injury to the liver is also unavoidable during the transplantation procedure. This directly impacts liver viability with consequences ranging from mild organ dysfunction to hepatic failure. Hepatic I/R injury has been extensively studied but there is still much to be understood. Paper I studied the effect of portal triad clamping (PTC) on hepatic metabolism in patients undergoing liver resection using intrahepatic microdialysis to monitor glucose, lactate and pyruvate as markers of ischemia and glycerol as a marker of cell membrane damage. The lactate/pyruvate ratio (L/Pr) was also calculated. PTC induced considerable alterations, with anaerobic metabolism and increased glycogenolysis manifested by increased levels of glucose, lactate and L/Pr and cell membrane damage evidenced by increased levels of glycerol Papers II and III were methodological studies of hepatic microdialysis in pig models. We could show that microdialysis catheters with membrane cut-off of 20 and 100 kDa could be used equally in hepatic microdialysis for monitoring the products of glucose metabolism and glycerol. However, microdialysis performed using a catheter placed directly in the middle hepatic vein was not equivalent to direct intrahepatic monitoring of the same metabolites. Paper IV investigated the effects of warm I/R injury induced by PTC on hepatic morphology at the ultrastructural level and on the expression of the thioredoxin and glutaredoxin redox systems. On electron microscopy, a significant loss of the liver sinusoidal endothelial cell (LSEC) lining was observed and a decrease of hepatocyte microvilli. Hepatocellular morphology was well preserved apart from the appearance of crystalline mitochondrial inclusions. After reperfusion the LSEC lining showed signs of reactivation. No significant changes were observed in the TRX and GRX redox systems. Paper V explored the value of L/Pr measured by microdialysis as a marker for ischemic complications in 45 patients undergoing liver transplantation (LT). Raised L/Pr defined according to protocol were identified in 24 patients but none were predictive of clinically significant ischemic complications. L/Pr is thus not a reliable marker of clinically significant ischemic events after LT. Paper VI evaluated microdialysis as a postoperative monitoring tool for detection of acute cellular rejection (ACR) in patients undergoing LT. ACR was diagnosed in 33 of 71 transplanted patients. Results revealed metabolic patterns indicating a possible relation between the severity of primary I/R injury and the development of ACR. In conclusion, warm ischemia induced by PTC causes significant alterations in hepatic metabolism and ultrastructure. L/Pr measured by microdialysis is not a reliable marker for detecting clinically significant ischemic complications early after LT. Primary I/R injury experienced by the organ during the LT procedure may be associated with the development of ACR. It may be possible to monitor larger molecules using microdialysis with 100kDa catheters without affecting the monitoring of small molecules. To get reliable results when monitoring hepatic metabolism by microdialysis the catheter should be placed intrahepatically.
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| 2. |
- D'Souza, Melroy A., et al.
(författare)
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Hepatopancreatoduodenectomy –a controversial treatment for bile duct and gallbladder cancer from a European perspective
- 2020
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Ingår i: HPB. - : Elsevier BV. - 1365-182X. ; 22:9, s. 1339-1348
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. Method: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. Results: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. Conclusion: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.
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| 3. |
- D'souza, Melroy A., et al.
(författare)
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The clinicopathological spectrum and management of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B)
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 48:4, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is a rare but increasingly diagnosed clinical entity. Typical cholangioscopic findings usually include intraductal protruding papillary tumors that secrete mucus.METHODS: Clinical, radiological and histopathological data of seven consecutive patients who were found to have IPMN-B were analyzed.RESULTS: Six of the seven patients presented with obstructive jaundice/cholangitis as the presenting complaint. ERCP and other imaging were equivocal in five of these patients and peroral cholangioscopy (POCS, single-operator cholangioscopy system) was performed. This revealed mucin-producing intraductal tumors with numerous frond-like papillary projections; a macroscopic appearance consistent with IPMN-B. Preoperative biopsy revealed adenoma, with low-grade dysplasia in two patients and high-grade dysplasia in three. Three patients underwent Whipple resection; one underwent total pancreatectomy with left hepatectomy, one patient a pancreas preserving duodenectomy with common bile duct reimplantation and one patient an extended right hepatectomy. These patients were found to have IPMN-B with adenomatous changes with varying grades of dysplasia and even cholangiocarcinoma on final histopathology. One patient first underwent endoscopic papillectomy and on follow-up was found to have cholangiocarcinoma with metastases to the liver.CONCLUSION: POCS can be a key diagnostic investigation in the evaluation of patients with papillary tumors of the bile duct. IPMN-B has a heterogenous pathology and varying grades of dysplasia and even carcinoma may exist in the same patient. Surgical management should be radical and based on tumor extent.
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| 4. |
- Gilg, Stefan, et al.
(författare)
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Molecular adsorbent recirculating system treatment in patients with post-hepatectomy liver failure : Long-term results of a pilot study
- 2022
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Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 111:3, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post-hepatectomy liver failure (PHLF) is the leading cause of postoperative mortality following major liver resection. Between December 2012 and May 2015, 10 consecutive patients with PHLF (according to the Balzan criteria) following major/extended hepatectomy were included in a prospective treatment study with the molecular adsorbent recirculating system (MARS). Sixty- and 90-day mortality rates were 0% and 10%, respectively. Of the nine survivors, four still had liver dysfunction at 90 days postoperatively. One-year overall survival (OS) of the MARS-PHLF cohort was 50%. The present study aims to assess long-term outcome of this cohort compared to a historical control cohort.Methods: To compare long-term outcome of the MARS-PHLF treatment cohort with PHLF patients not treated with MARS, the present study includes all 655 patients who underwent major hepatectomy at Karolinska University Hospital between 2010 and 2018. Patients with PHLF were identified according to the Balzan criteria.Results: The cohort was split into three time periods: pre-MARS period (n = 192), MARS study period (n = 207), and post-MARS period (n = 256). The 90-day mortality of patients with PHLF was 55% (6/11) in the pre-MARS period, 14% during the MARS study period (2/14), and 50% (3/6) in the post-MARS period (p = 0.084). Median OS (95% confidence interval (CI)) was 37.8 months (29.3–51.7) in the pre-MARS cohort, 57 months (40.7–75.6) in the MARS cohort, and 38.8 months (31.4–51.2) in the post-MARS cohort. The 5-year OS of 10 patients included in the MARS study was 40% and the median survival 11.6 months (95% CI: 3 to not releasable). In contrast, for the remaining 21 patients fulfilling the Balzan criteria during the study period but not treated with MARS, the 5-year OS and median survival were 9.5% and 7.3 months (95% CI, 0.5–25.9), respectively (p = 0.138)).Conclusions: MARS treatment may contribute to improved outcome of patients with PHLF. Further studies are needed.The initial pilot study was registered at ClinicalTrials.gov (NCT03011424).
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| 5. |
- Lluis, Nuria, et al.
(författare)
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Intraductal papillary neoplasms of the bile duct: a European retrospective multicenter observational study (EUR-IPNB study)
- 2023
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Ingår i: International Journal of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 1743-9191 .- 1743-9159. ; 109:4, s. 760-771
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose:Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers. Methods:A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days. Results:A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 (P=0.016), intrahepatic versus extrahepatic tumor (P=0.027), single versus multiple tumors (P=0.007), those who underwent hepatic versus pancreatic resection (P=0.017), or achieved versus failed TO (P=0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P=0.03) was an independent prognostic factor of poor overall survival. Conclusions:Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.
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| 6. |
- Lluís, Núria, et al.
(författare)
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Intraductal papillary neoplasms of the bile ducts : a comparative study of a rare disease in Europe and Nagoya, Japan
- 2024
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Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 26:4, s. 565-575
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. Methods: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. Results: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. Discussion: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.
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