Morbidity and mortality after hepatectomy for perihilar cholangiocarcinoma are known to be high. However, reported postoperative outcomes vary, with notable differences between Western and Asian ...series. We aimed to determine morbidity and mortality rates after major hepatectomy in patients with perihilar cholangiocarcinoma and assess differences in outcome regarding geographic location and hospital volume.
A systematic review was performed by searching the MEDLINE and EMBASE databases through November 20, 2017. Risk of bias was assessed and meta-analysis and metaregression were performed using a random effects model.
A total of 51 studies were included, representing 4,634 patients. Pooled 30-day and 90-day mortality were 5% (95% CI 3%–6%) and 9% (95% CI 6%–12%), respectively. Pooled overall morbidity and severe morbidity were 57% (95% CI 50%–64%) and 40% (95% CI 34%–47%), respectively. Western studies compared with Asian studies had a significantly higher 30-day mortality, 90-day mortality, and overall morbidity: 8% versus 2% (P < .001), 12% versus 3% (P < .001), and 63% versus 54% (P = .048), respectively. This effect on mortality remained significant after correcting for hospital volume. Univariate metaregression analysis showed no influence of hospital volume on mortality or morbidity, but when corrected for geographic location, higher hospital volume was associated with higher severe morbidity (P = .039).
Morbidity and mortality rates after major hepatectomy for perihilar cholangiocarcinoma are high. The Western series showed a higher mortality compared with the Asian series, even when corrected for hospital volume. Standardized reporting of outcomes is necessary. Underlying causes for differences in outcomes between Asian and Western centers, such as differences in treatment strategies, should be further analyzed.
Background
Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma ...(pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers.
Methods
Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT.
Results
A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3–23).
Conclusion
Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed.
Outcomes for the four anatomical subtypes of biliary tract carcinoma (BTC) - intrahepatic, perihilar and distal cholangiocarcinoma (ICC, PHCC, DCC) and gallbladder carcinoma (GBC) - are often ...combined. However, large cohorts comparing short- and long-term outcomes for the anatomical subtypes of BTC are lacking.
All patients who underwent resection for pathology proven ICC, PHCC, DCC or GBC (2000–2016) from a single Western high-volume center were retrospectively selected. Clinicopathological characteristics, short- and long-term outcomes were compared between the four anatomical subtypes.
Overall, 361 patients with resected BTC were included (33 ICC, 135 PHCC, 148 DCC, 45 GBC). Clavien-Dindo grade III or higher complications were 48%, 51%, 36% and 8% (p < 0.001) and 90-day mortality was 9%, 15%, 3%, 4% (p < 0.001), for ICC, PHCC, DCC, GBC. Median overall survival was 37, 42, 29 and 41 months (p = 0.722), for ICC, PHCC, DCC, GBC. Five-year survival ranged between 29% and 37%. Anatomical subtype was not an independent predictor for overall survival.
In this large single-center cohort of resected BTC, major morbidity and 90-day mortality varied between the four anatomical subtypes of BTC, mainly due to differences in surgical approach However, a significant difference in overall survival was not detected.
•Induction therapy seems safe and promising for patients with cholangiocarcinoma.•There are still major differences in terms of resectability criteria.•Prospective randomized controlled trials are ...warranted to confirm these results.
According to international guidelines, induction therapy may be considered in selected patients with initially unresectable locally advanced cholangiocarcinoma. The criteria for (un)resectability in cholangiocarcinoma varies between studies and no consensus-based agreement is available about these criteria. By performing a systematic literature review, we aimed to investigate the efficacy and safety of systemic induction therapy in initially unresectable locally advanced perihilar (pCCA) and intrahepatic cholangiocarcinoma (iCCA) and summarize resectability criteria used across studies.
A literature search was performed in PubMed, EMBASE, Web of Science and Cochrane library to identify studies on systemic induction therapy in locally advanced pCCA and/or iCCA. The primary outcome was resection rate (RR) after induction therapy and secondary outcomes were overall survival (OS) and objective response rate (ORR).
Ten studies with a total of 1167 patients met the inclusion criteria and were included in this review. Among these patients, 334 (28.6%) were treated with systemic induction therapy. Across the studies, different types of chemotherapy regimens were administered (e.g., gemcitabine (based) chemotherapy and 5-FU (based) chemotherapy). Only six studies provided sufficient data and were used to analyze pooled (radical) resection rates. After induction therapy, 94 patients (39.2%) underwent a resection, of which R0 resections (22.9%). Pooled data on OS showed, better OS for chemotherapy plus resection versus chemotherapy only (pooled HR = 0.31, 95% CI = 0.19–0.50; P value < 0.0001).
Adequately selected patients with locally advanced pCCA or iCCA may benefit from induction therapy followed by surgical resection. Prospective randomized controlled trials are warranted.
Standard portal vein resection (PVR) has been proposed to improve oncological outcomes in patients with perihilar cholangiocarcinoma (PHC), however it potentially introduces an increased risk of ...morbidity. The policy in Amsterdam UMC(AMC) is to resect the portal vein bifurcation selectively when involved, while in Charité-Universitätsmedizin Berlin, standard PVR is performed with right trisectionectomy. The objective of this study was to analyze postoperative outcomes and survival after standard or selective PVR for PHC.
A retrospective study was performed including PHC-patients undergoing right-sided resection in Amsterdam (2000–2018) and Berlin (2005–2015). Primary outcomes were 90-day mortality, severe morbidity (Clavien-Dindo≥3), and overall survival (OS). A propensity score comparison (1:1 ratio) was performed corrected for age/sex/ASA/jaundice/tumor diameter/N-stage/Bismuth-Corlette type-IV.
A total of 251 patients who underwent right-sided resection for PHC were evaluated: 87 in the selective (Amsterdam) and 164 in the standard PVR-group (Berlin). Major differences in baseline characteristics were observed, with higher ASA and AJCC-stage in the standard PVR-group (Berlin). Severe morbidity and 90-day mortality were comparable before matching (selective/Amsterdam:68% and 19%, standard/Berlin:61% and 17%,p = 0.284 and p = 0.746, respectively). After propensity score matching, both short term outcomes and OS were comparable (selective/Amsterdam (n = 45) 33 months (95%CI:20–45), standard/Berlin (n = 45) 31 months (95%CI:24–38,p = 0.747)).
In this combined cohort, standard PVR was not associated with increased severe morbidity or mortality. After propensity score matching, survival was comparable after selective (Amsterdam) and standard PVR (Berlin).
Choledochoduodenostomy (CD) is believed to cause certain long-term complications, such as sump syndrome and reflux gastritis. Therefore, CD is considered inferior to a Roux-and-Y hepaticojejunostomy ...(HJ). The aim of this study was to compare short- and long-term outcomes following CD and HJ for benign biliary diseases.
This was a retrospective, matched case-control study of patients undergoing biliary-digestive anastomosis for benign diseases between 2000 and 2016 in a tertiary centre. Patients undergoing CD and HJ were matched 1:1 based on age, sex, ASA-classification, indication, history of abdominal surgery or acute cholecystitis/pancreatitis. Short- and long-term outcomes were compared.
Of 336 patients undergoing biliary-digestive anastomoses, 27 patients underwent CD. Matching resulted in two comparable groups of 26 patients each. Overall morbidity after HJ and CD was comparable: 30.8% versus 26.9% (p>0.999). Long-term complications occurred in 23.1% after HJ, and in 50% after CD (p=0.118). After CD, 2 patients (7.7%) developed sump syndrome. Both patients with an anastomotic stricture after HJ could be managed by endoscopic/radiological re-intervention, whilst all six patients with a stricture after CD required surgical re-intervention (p=0.016).
Although short-term complications were comparable, the number of anastomotic strictures was higher in patients undergoing CD. We therefore conclude that HJ is the biliary bypass of choice while CD should be performed in selected patients only.
In perihilar cholangiocarcinoma (PHC), interpretation of the resection specimen is challenging for pathologists and clinicians alike. Thorough and correct reporting is necessary for reliable ...interpretation of residual disease status. The aim of this study is to assess completeness of PHC pathology reports in a single center and assess what hampers interpretation of pathology reports by clinicians. Pathology reports of patients resected for PHC at a single expert tertiary center drafted between 2000 and 2018 were assessed. Reports were assessed regarding completeness, according to the guideline of the International Collaboration on Cancer Reporting (ICCR). A total of 146 reports were assessed. Prognostic tumor characteristics such as vasoinvasive growth and perineural growth were missing in 30/146 (34%) and 22/146 (15%), respectively. One or more planes were missing in 94/146 (64%) of the reports, with the periductal dissection plane missing in 51/145 (35%). Residual disease could be re-classified from R0 to R1 in 22 patients (15%). Reasons for R1 in these patients were the presence of a positive periductal dissection plane (
n
= 2), < 1-mm margin at the periductal dissection plane (
n
= 11), or liver parenchyma (
n
= 9). Completeness of reports improved significantly when drafted by an expert HPB pathologist. This study demonstrates that pathology reporting of PHC is challenging. Reports are frequently incomplete and often do not incorporate assessment of all resection planes and the dissection plane. The periductal dissection plane is frequently overlooked, but is a major cause of residual disease.
In this retrospective cohort study, the potential of gemcitabine (gem)/cisplatin (cis) chemotherapy as future preoperative therapy for patients with unresectable locally advanced or borderline ...resectable intrahepatic, perihilar, and mid-cholangiocarcinoma was investigated.
All patients with intrahepatic, perihilar, and mid-cholangiocarcinoma presented at Amsterdam UMC between January 2016 and October 2019 were included. The radiologic response after 3 and/or 6 cycles of gem/cis chemotherapy in patients with unresectable locally advanced or borderline resectable disease was derived from the original radiologic reports and subsequently re-evaluated for surgical exploration by consensus reading of 2 HPB surgeons and 1 radiologist.
Overall, 65 of 364 patients had a locally advanced or borderline resectable disease. Twenty-eight patients were treated with palliative chemotherapy, including 25 (89.3%) patients who received more than 3 cycles. Twenty-two patients (88.0%) and 13 patients (46.4%) showed RECIST stable disease or partial response after 3 and 6 cycles of chemotherapy, respectively. Three patients experienced grade 3 adverse events. Consensus reading concluded that exploration could have been reconsidered in 7 of 28 patients (25.0%).
Gem/cis may be a safe and feasible preoperative treatment in initially unresectable locally advanced or borderline resectable cholangiocarcinoma. In addition, the findings of this study support to always rediscuss patients with stable or responsive disease in multidisciplinary team meetings to reconsider resection. Besides, prospective studies are needed to investigate this effect further and, based on these preliminary data, seem feasible in this setting.
The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and ...its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm
2
(p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm
2
(p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm
2
(p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters.
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