Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial.

BACKGROUND: Despite the increasing efficacy of chemotherapy, permanently unresectable colorectal liver metastases are associated with poor long-term survival. We aimed to assess whether liver transplantation plus chemotherapy could improve overall survival. METHODS: TransMet was a multicentre, open-label, prospective, randomised controlled trial done in 20 tertiary centres in Europe. Patients aged 18-65 years, with Eastern Cooperative Oncology Group performance score 0-1, permanently unresectable colorectal liver metastases from resected BRAF-non-mutated colorectal cancer responsive to systemic chemotherapy (≥3 months, ≤3 lines), and no extrahepatic disease, were eligible for enrolment. Patients were randomised (1:1) to liver transplantation plus chemotherapy or chemotherapy alone, using block randomisation. The liver transplantation plus chemotherapy group underwent liver transplantation for 2 months or less after the last chemotherapy cycle. At randomisation, the liver transplantation plus chemotherapy group received a median of 21·0 chemotherapy cycles (IQR 18·0-29·0) versus 17·0 cycles (12·0-24·0) in the chemotherapy alone group, in up to three lines of chemotherapy. During first-line chemotherapy, 64 (68%) of 94 patients had received doublet chemotherapy and 30 (32%) of 94 patients had received triplet regimens; 76 (80%) of 94 patients had targeted therapy. Transplanted patients received tailored immunosuppression (methylprednisolone 10 mg/kg intravenously on day 0; tacrolimus 0·1 mg/kg via gastric tube on day 0, 6-10 ng/mL days 1-14; mycophenolate mofetil 10 mg/kg intravenously day 0 to <2 months and switch to everolimus 5-8 ng/mL), and postoperative chemotherapy, and the chemotherapy group had continued chemotherapy. The primary endpoint was 5-year overall survival analysed in the intention to treat and per-protocol population. Safety events were assessed in the as-treated population. The study is registered with ClinicalTrials.gov (NCT02597348), and accrual is complete. FINDINGS: Between Feb 18, 2016, and July 5, 2021, 94 patients were randomly assigned and included in the intention-to-treat population, with 47 in the liver transplantation plus chemotherapy group and 47 in the chemotherapy alone group. 11 patients in the liver transplantation plus chemotherapy group and nine patients in the chemotherapy alone group did not receive the assigned treatment; 36 patients and 38 patients in each group, respectively, were included in the per-protocol analysis. Patients had a median age of 54·0 years (IQR 47·0-59·0), and 55 (59%) of 94 patients were male and 39 (41%) were female. Median follow-up was 59·3 months (IQR 42·4-60·2). In the intention-to-treat population, 5-year overall survival was 56·6% (95% CI 43·2-74·1) for liver transplantation plus chemotherapy and 12·6% (5·2-30·1) for chemotherapy alone (HR 0·37 [95% CI 0·21-0·65]; p=0·0003) and 73·3% (95% CI 59·6-90·0) and 9·3% (3·2-26·8), respectively, for the per-protocol population. Serious adverse events occurred in 32 (80%) of 40 patients who underwent liver transplantation (from either group), and 69 serious adverse events were observed in 45 (83%) of 54 patients treated with chemotherapy alone. Three patients in the liver transplantation plus chemotherapy group were retransplanted, one of whom died postoperatively of multi-organ failure. INTERPRETATION: In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases. FUNDING: French National Cancer Institute and Assistance Publique-Hôpitaux de Paris.

Comprehensive Review of Future Liver Remnant (FLR) Assessment and Hypertrophy Techniques Before Major Hepatectomy: How to Assess and Manage the FLR.

BACKGROUND: The regenerative capacities of the liver and improvements in surgical techniques have expanded the possibilities of resectability. Liver resection is often the only curative treatment for primary and secondary malignancies, despite the risk of post-hepatectomy liver failure (PHLF). This serious complication (with a 50% mortality rate) can be avoided by better assessment of liver volume and function of the future liver remnant (FLR). OBJECTIVE: The aim of this review was to understand and assess clinical, biological, and imaging predictors of PHLF risk, as well as the various hypertrophy techniques, to achieve an adequate FLR before hepatectomy. METHOD: We reviewed the state of the art in liver regeneration and FLR hypertrophy techniques. RESULTS: The use of new biological scores (such as the aspartate aminotransferase/platelet ratio index + albumin-bilirubin [APRI+ALBI] score), concurrent utilization of 99mTc-mebrofenin scintigraphy (HBS), or dynamic hepatocyte contrast-enhanced MRI (DHCE-MRI) for liver volumetry helps predict the risk of PHLF. Besides portal vein embolization, there are other FLR optimization techniques that have their indications in case of risk of failure (e.g., associating liver partition and portal vein ligation for staged hepatectomy, liver venous deprivation) or in specific situations (transarterial radioembolization). CONCLUSION: There is a need to standardize volumetry and function measurement techniques, as well as FLR hypertrophy techniques, to limit the risk of PHLF.

Impact of universal hepatitis B virus (HBV) screening using chemotherapy orders on the HBV reactivation in cancer patients.

INTRODUCTION: Hepatitis B virus (HBV) reactivation (HBVr) induced by chemotherapy in patients with resolved or chronic infection can lead to severe consequences. Despite recommendations, rates of HBV screening before chemotherapy are low due to poor recognition of risk factors by clinicians. The aim of the study is to assess whether routine HBV screening using universal HBV screening on chemotherapy orders (CO) could reduce HBVr incidence. METHODS: This is a 1-year retrospective single-center observational study of patients who received intravenous chemotherapy post implementation of CO. We compared the incidence of HBVr in three groups of patients: those screened through CO (group 1), those screened by the medical team (group 2), and those not screened (group 3). RESULTS: On a total of 1374 patients, 179 of 206 patients were screened as requested on CO (group 1) and 421 by the medical team (group 2), whereas 747 patients were not screened (group 3). Only one HBVr occurred, and no difference was seen on the incidence of HBVr between group 1 and group 3 (0% vs 0.1%; p = 1.00), probably because of a lack of follow-up after chemotherapy. Follow-up for HBVr was imperfect in group 1 and group 2 (16.7% vs 5.6%; p = 0.32). Screening was done for 92% of patients on anti-CD20 therapy. In group 3, 89 patients had ALT elevation during chemotherapy but only 17 (19%) were tested for HBVr. CONCLUSION: Systematic HBV detection requested on CO is an effective way to obtain a high percentage of patients with adequate screening, particularly when chemotherapy is at high risk of HBVr. Nevertheless, this screening method do not guarantee optimal follow-up and requires improvements.

Hypokalemia, hypomagnesemia, and hyponatremia are associated with acute kidney injury in patients treated with cisplatin.

INTRODUCTION: Cisplatin-associated acute kidney injury (C-AKI) is common. Predictive factors include age >60 years, hypertension, cisplatin dose, diabetes, and serum albumin < 3.5 g/L. The association between C-AKI and hypokalemia, hypomagnesemia or hyponatremia has not been well characterized. METHODS: Data from a previous retrospective observational study was obtained. Patients were separated into three groups with similar cisplatin doses and schedules. Group A received cisplatin 60-100 mg/m2 every three weeks with laboratory assessments before treatment, group B received cisplatin 60-75 mg/m2 every three weeks with laboratory assessments before days 1 and 8 and group C had weekly cisplatin 40 mg/m2 with weekly laboratories assessments. The association between hypomagnesemia, hypokalemia, hyponatremia, and risk of AKI was determined using a counting process specification of Cox's regression models. RESULTS: A total of 1301 patients were separated into groups A (n = 713), B (n = 204), and C (n = 384). The proportion of patients with at least one event of hypokalemia, hypomagnesemia, or hyponatremia was lower in group A (29.2%, 57.6%, 36.2%) compared to groups B (43.6%, 67.2%, 59.8%) and C (49.0%, 78.7%, 51.0%). The incidence of all grade C-AKI was 35.6% (group A), 46.6% (group B), and 18.2% (group C). In group A, the risk of AKI doubled with hyponatremia or hypomagnesemia and tripled with hypokalemia. This association was not seen with other groups. CONCLUSION: Among patients with the highest doses of cisplatin, the presence of one electrolyte disorder was associated with an increased risk of C-AKI. Other studies are needed to characterize the presence of an electrolyte disorder as a predictive risk factor of C-AKI in this subpopulation.

Waiting for bile duct dilation before repair of bile duct injury: a worthwhile strategy?

BACKGROUND: Hepaticojejunostomy (HJ) is the gold standard procedure for repairing major bile duct injury (BDI). Dilation status of the BD before repair has not been assessed as a risk factor for anastomotic stricture. METHOD: This retrospective single-centre study was performed on a population of 87 patients with BDI repaired by HJ between 2007 and 2021. Dilation status was assessed preoperatively, and dilation was defined as the presence of visible peripheral intrahepatic BDs with remaining BD diameter > 8 mm. The short- and long-term outcomes of HJ were assessed according to preoperative dilation status. RESULTS: Before final repair, the BDs were dilated (dBD) in 56.3% of patients and not dilated (ND) in 43.7%. Patients with ND at the time of repair had more severe BDI injury than those with dBD (94.7% vs. 77.6%, p = 0.026). The rate of preoperative cholangitis was lower in patients with ND than in those with dBD (10.5% vs. 44.9%, p = 0.001). The rate of short-term morbidity after HJ was 33.3% (ND vs. dBD: 38.8% vs. 26.3%, p = 0.32). Long-term anastomotic stricture rate was 5.7% with a mean follow-up period of 61.3 months. There were no differences in long-term biliary complications according to dilation status (ND vs. dBD: 12.2% vs. 10.5%, p = 1). CONCLUSION: Dilation status of the BD before HJ for BDI seemed to have no impact on short- or long-term outcomes. Both surgical and radiological external biliary drainages after BDI appear to be acceptable options to reduce cholangitis before repair without increasing risk for long-term anastomotic stricture.

Liver transplantation and hepatocellular carcinoma: is TIPS deleterious? A multicentric retrospective study of the ARCHET research group with propensity score matching.

PURPOSE: A transjugular intrahepatic portosystemic shunt (TIPS) before the liver transplantation (LT) has been considered a contraindication in cases of hepatocellular carcinoma (HCC) because of the risk of tumour growth. We aimed to assess the impact of TIPS on incidental HCC and oncological outcomes in transplanted patients with pre-existing HCC. METHODS: All consecutive transplanted patients for cirrhosis who had a previous TIPS with or without HCC were included. Between 2007 and 2014, 1912 patients were transplanted. We included 122 (6.3%) patients having TIPS before LT. A 1:3 matched cohort of 366 patients (18.9%) having LT without previous TIPS was selected using a propensity score. Incidental HCC rate and risk factor of HCC recurrence were evaluated using multivariate analysis with a competing risk model. RESULTS: Before LT, in the TIPS group, 27 (22.1%) had an HCC vs. 81 (22.1%) in the control group (p = 1). The incidental HCC rate was similar: 10.5% (10/95) in the TIPS group vs. 6.3% (18/285) in the control group (p = 0.17). Recurrence occurred in 1/27 (3.7%) patient in the TIPS group and in 7/81 (8.6%) patients in the control group, without significant difference (p = 0.51). After multivariate regression, patient's gender (p < 0.01) was significantly associated with HCC recurrence while a tumour within Milan criteria (p = 0.01, sHR: 0.17 [0.04; 0.7]) and an incidental HCC (p<0.01) were found to be protector factors against HCC recurrence. CONCLUSION: TIPS did not worsen the prognosis of transplanted patients for HCC. TIPS should no longer be contraindicated for oncological reasons in patients with HCC waiting for an LT.

Cyclin-dependent kinase 4/6 inhibitor treatment use in women treated for advanced breast cancer: Integrating ASCO/NCODA patient-centered standards in a community pharmacy.

BACKGROUND: Outpatients treated with oral anti-cancer drugs, including selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), may benefit from a pharmacy practice setting adapted to support proper oral anti-cancer drug monitoring. This real-world study aimed to characterize patient-centered pharmacy practice aligned with American Society of Clinical Oncology (ASCO)/National Community Oncology Dispensing Association (NCODA) standards and to describe its impact on CDK4/6i treatment use. METHODS: This retrospective study included women with confirmed hormone receptor-positive/human epidermal growth factor 2 negative locally advanced or metastatic breast cancer treated with either palbociclib, abemaciclib or ribociclib combined with letrozole or fulvestrant. Pharmacists collected patient characteristics, clinical activities, and treatment patterns using data from the pharmacy chart. CDK4/6i treatment adherence rates were estimated based on medication claims data. Time-to-treatment discontinuation, a proxy for time-to-event, was assessed using the Kaplan-Meier estimate. RESULTS: Of the 195 patients assessed for eligibility, 65 were included in this study. The median observation duration was 13.6 months. An average of seven pharmaceutical care activities (range 2.8-21.7) per patient was documented for each treatment cycle. The mean proportion of days covered was 89.6%. The median time-to-treatment discontinuation was estimated at 44.2 months in patients treated with CDK4/6i + letrozole and 17.0 months in patients treated with CDK4/6i + fulvestrant. The average relative dose intensity was 85%, and the benefits of treatment were maintained regardless of the relative dose intensity levels. CONCLUSION: A structured patient-centered pharmacy practice model integrating the ASCO/NCODA patient-centered standards and ongoing communication with patients and healthcare providers ensure timely refills, close monitoring, and allows patients to achieve high adherence and persistence rates comparable to those reported in clinical trials.

Preemptive wirsungostomy: a safe fistula for avoiding a dreadful fistula in elective or planned pancreatoduodenectomy.

BACKGROUND: High-risk pancreatic anastomosis can lead to a high mortality rate after PD due to the development of postoperative pancreatic fistula (POPF). Performing a wirsungostomy by externalizing the pancreatic duct is a poorly known alternative to anastomosis which could reduce the risk of POPF and the associated severe morbidity METHODS: We retrospectively evaluated patients who underwent primary wirsungostomy with PD from January 2007 to December 2021 in our tertiary referral center. Rates of morbidity and mortality with long-term pancreatic functions were studied. RESULTS: Sixty patients were included. The median Updated Alternative Fistula Risk Score (ua-FRS) was 52%, with 95% patients in the high-risk ua-FRS category and 88.3% patients with stage D risk of developing POPF according to the classification of the ISGPS. The mortality rate was 3.3%, and overall 90-day postoperative morbidity was 63.7% with 50% of patients developing major complications. Mean follow-up was 29.8 months. Twelve patients (20%) became diabetic and 35 patients (58.3%) had preserved pancreatic endocrine function CONCLUSION: Preemptive wirsungostomy with PD could be an appropriate procedure for patients with high-risk pancreatic anastomosis. The high associated morbidity could be compromised by the low mortality and preservation of endocrine function compared to total pancreatectomy or severe POPF.

Use of midostaurin in mixed phenotype acute leukemia with FLT3 mutation: A case series.

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia where blasts present phenotypes from more than one lineage. A poor prognostic has been associated with this disease, and limited data are currently available to guide the choice of therapy. Regarding FLT3-positive MPAL, only one case treated with midostaurin has been published to date. Here, we report the successful use of midostaurin to treat three FLT3-positive MPAL T/myeloid and B/myeloid patients. Midostaurin was successfully added to intensive induction (two patients) and consolidation chemotherapy (three patients) without significant adverse events requiring a dose adjustment or discontinuation. The therapy received resulted in complete remission for two patients and complete remission with an incomplete hematologic recovery for the third. All patients proceeded to HSCT and stayed in remission after an extended follow-up respectively at 28, 31, and 11 months later. These results suggest that the addition of midostaurin during induction and consolidation therapy may represent a treatment option for FLT3-positive MPAL.

Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review.

OBJECTIVE: The aim of this article is to conduct a literature review on first-generation TRK inhibitors (TRKi), namely entrectinib and larotrectinib, to describe the most common adverse events (AEs) and their management in adults. METHODS: A search strategy was conducted in MEDLINE, EMBASE, and Google Scholar using a list of predetermined keywords. Peer-reviewed articles written in English and published through June 2021 were included. Articles covered included randomized clinical trials and expert recommendations, as well as patent and other types of reviews. RESULTS: The discussed AEs include weight gain and withdrawal pain, as well as neuromuscular, central nervous system (dysesthesias and peripheral sensory neuropathies, dizziness and ataxia, and dysgeusia), gastrointestinal (nausea, vomiting, and diarrhea), and respiratory symptoms. Additionally, several AEs encountered with entrectinib specifically (cognitive and vision disorders, congestive heart failure, QTc elongation, and skeletal fractures) are discussed. First, an overall mechanism of action explaining these AEs is presented. Then, for each AE, incidence and severity are stated and followed by practical management recommendations. While nearly all AEs were reversible upon TRKi suspension, the proposed managements are mainly constituted of pharmacological and non-pharmacological interventions. CONCLUSION: With the estimated growth of gene sequencing in the coming years, it is foreseeable that TRKi will take a larger position in the oncologic therapeutic arsenal. Therefore, adequate management of AEs associated with TRKi in adults should be a prime focus.

Liver transplantation for iatrogenic bile duct injury during cholecystectomy: a French retrospective multicenter study.

BACKGROUND: Major bile duct injuries (BDI) following cholecystectomy require complex reconstructive surgery. The aim was to collect the liver transplantations (LT) performed in France for major BDI following cholecystectomy, to analyze the risk factors and to report the results. METHODS: National multicenter observational retrospective study. All the patients who underwent a LT in France between 1994 and 2017, for BDI following cholecystectomy, were included. RESULTS: 30 patients were included. 25 BDI occurred in non hepato-biliary expert centers, 20 were initially treated in these centers. Median time between injury and LT was 3 years in case of an associated vascular injury (11 injuries), versus 11.7 years without vascular injury (p = 0.006). Post-transplant morbidity rate was 86.7%, mortality 23.5% at 5 years. CONCLUSION: Iatrogenic BDI remains a real concern with severe cases, associated with vascular damages or leading to cirrhosis, with no solution but LT. It is associated with high morbidity and not optimal results. This enlights the necessity of early referral of all major BDI in expert centers to prevent dramatic outcome. Decision to perform transplantation should be taken before dismal infectious situations or biliary cirrhosis and access to graft should be facilitated by Organ Sharing Organizations.

Hepatocellular Adenoma Risk Factors of Hemorrhage: Size Is Not the Only Concern!: Single-center Retrospective Experience of 261 Patients.

OBJECTIVE: Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) to define a better management strategy. SUMMARY BACKGROUND DATA: HCA is a rare benign liver tumor with severe complications: malignant transformation that is rare (5%-8%) and more often, hemorrhage (20%-27%). To date, only size > 5 cm and histological subtype (possibly sonic hedgehog) are associated with bleeding, but these criteria are not clearly established. METHODS: We retrospectively collected data from a cohort of 268 patients with HCA managed in our tertiary center, from 1984 to 2020 and focused on clinical bleeding. Hemorrhage was considered severe when it required intensive care and moderate when bleeding symptoms required a hospitalization. We included 261 patients, of whom 130 (49.8%) had multiple HCAs or liver adenomatosis. All surgical specimen and liver biopsy were reviewed by an experienced liver pathologist and reclassified in the light of the current immunohistochemistry. Mean duration of follow-up was 93.3 months (range 1-363). We analyzed type, frequency, consequences of bleeding, and risk factors among clinical data and HCA characteristics. RESULTS: Eighty-three HCA (31.8%) were hemorrhagic. There were 4 pregnant women with 1 newborn death. One patient died before treatment. Surgery was performed in 78 (94.0%) patients. Mortality was nil and severe complications occurred in 11.5%. Multivariate analysis identified size (OR 1.02 [1.01-1.02], P < 0.001), shHCA (OR 21.02 [5.05-87.52], P < 0.001), b-catenin mutation on exon 7/8 (OR 6.47 [1.78-23.55], P = 0.0046), chronic alcohol consumption (OR 9.16 [2.47-34.01], P < 0.001) as independent risk factors of clinical bleeding. CONCLUSIONS: This series, focused on the hemorrhagic risk of HCA, shows that size, but rather more molecular subtype is determinant in the natural history of HCA.

Effect of mannitol on acute kidney injury induced by cisplatin.

PURPOSE: Acute kidney injury (AKI) is a frequent dose-limiting toxicity induced by cisplatin. Mannitol has been used in hydration protocols to mitigate this adverse event but its role remains controversial. The aim of this study is to define the impact of mannitol on AKI in patients receiving cisplatin. METHODS: This retrospective observational study was conducted in cancer patients who received at least one dose of cisplatin between September 2010 and December 2016 at the Centre hospitalier de l'Université de Montréal. The primary outcome of this study was the comparison of all grade cisplatin-associated AKI between hydration protocols with or without mannitol. RESULTS: A total of 1821 patients were included of which 658 received mannitol whilst 1163 received hydration alone. The risk of all grade cisplatin-associated AKI was significantly lower for the mannitol group (Hazard Ratio (HR) = 0.62; 95% CI [0.42, 0.89]). This result was mainly driven by gynecologic (HR = 0.50), upper gastrointestinal (HR = 0.32), urinary tract malignancies (HR = 0.29) and lymphoma (HR = 0.33). No significant difference was seen for head and neck (HN), lung, germ cells and other cancers. However, HN cancers patients receiving mannitol had fewer grade 2 and 3 AKI. Significantly fewer AKI events were observed in HN, lung, upper gastrointestinal and urinary tract cancer when mannitol was added for cisplatin dose <75 mg/m2. CONCLUSION: Although the results were generally driven by a decrease of grade 1 AKI for most cancers, the greatest benefit of mannitol was seen with cisplatin doses lower than 75 mg/m2 and should probably be reinstated in this setting.

Risks of hepatitis C virus reactivation in a real-life population of oncology patients treated in an academic center.

BACKGROUND: Chemotherapy has been associated with a theoretical risk of hepatitis C virus (HCV) reactivation. However, little is known about the amplitude of viral replication and the incidence of subsequent hepatic exacerbation. METHOD: We aimed to describe the occurrence of hepatitis flare and HCV reactivation at our center. We included, over a period of 5 years, adult patients with chronic HCV receiving intravenous chemotherapy. We excluded patients with undetectable HCV RNA, hepatocellular carcinoma, liver metastases or other etiologies of hepatic disease. The primary objective was to identify hepatic flares (elevation of alanine aminotransferase 3 times above the upper limit of normal). Secondary objectives were to assess viral reactivation (HCVr, HCV-RNA ≥1 log10 IU/mL when compared to baseline value), hepatic decompensation, mortality and the impact on the chemotherapy. Descriptive statistics were used. RESULTS: A total of 11 patients with chronic HCV were identified among the 5761 oncology patients. Five patients experienced a hepatic flare with median maximal ALT value of 139 U/L (IQR 133-237). Only 2 patients met criteria for HCVr with a median RNA increase of 1.16 log IU/mL (IQR 1.1-1.2). One patient presented with both HCVr and a hepatic flare. Only one patient required chemotherapy discontinuation following hepatic flare. No hepatic decompensation or related mortality were observed. CONCLUSION: We identified a very small number of HCV cases among our population. We observed HCVr and hepatic flares, but only one consequence on cancer treatment. Nonetheless, HCV screening is encouraged among patients undergoing chemotherapy to allow close follow-up of hepatic function.

Does pre-operative embolization of a replaced right hepatic artery before pancreaticoduodenectomy for pancreatic adenocarcinoma affect postoperative morbidity and R0 resection? A bi-centric French cohort study.

BACKGROUND: Sacrificing a replaced right hepatic artery (rRHA) from the superior mesenteric artery is occasionally necessary to obtain an R0 resection after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). Preoperative embolization (PEA) of the rRHA has been proposed to avoid the onset of postoperative biliary and ischemic liver complications. METHODS: Eighteen patients with cephalic PA with an rRHA underwent PEA of the rRHA from 2013 to 2019. The monitoring after embolization and PD was systematic and included a clinical-biological evaluation and a computed tomography scan. This study aimed to determine the feasibility of PEA of the rRHA, postoperative morbidity at 90 days, and quality of oncologic resection after PD. RESULTS: Feasibility of PEA was 100% without complications. A PD was performed in 16/18 patients. Mortality was 2/16 with one death after septic shock with hepatic ischemia without an arterial obstruction. Overall morbidity was 44% including one hepatic abscess after hepatic ischemia (6%). Two resections were R1 (<1 mm) in contact with the origin of the rRHA (2/4 R1). CONCLUSION: PEA of the rRHA before PD was safe and reproducible. PEA of the rRHA followed by en bloc PD resection seems to limit the risk of bilio-hepatic ischemia and could facilitate oncologic resection.

Radiological Simultaneous Portohepatic Vein Embolization (RASPE) Before Major Hepatectomy: A Better Way to Optimize Liver Hypertrophy Compared to Portal Vein Embolization.

OBJECTIVE: The aim of this retrospective study was to compare portal vein embolization (PVE) and radiologica simultaneous portohepatic vein embolization (RASPE) for future liver remnant (FLR) growth in terms of feasibility, safety, and efficacy. SUMMARY OF BACKGROUND DATA: After portal vein embolization (PVE), 15% of patients remain ineligible for hepatic resection due to insufficient hypertrophy of the FLR. RASPE has been proposed to induce FLR growth. MATERIALS AND METHODS: Between 2016 and 2018, 73 patients were included in the study. RASPE was proposed for patients with a ratio of FLR to total liver volume (FLR/TLV) of <25% (RASPE group). This group was compared to patients who underwent PVE for a FLR/TLV <30% (PVE group). Patients in the 2 groups were matched for age, sex, type of tumor, and number of chemotherapy treatments. FLR was assessed by computed tomography before and 4 weeks after the procedure. RESULTS: The technical success rate in both groups was 100%. Morbidity post-embolization, and the time between embolization and surgery were similar between the groups. In the PVE group, the FLR/TLV ratio before embolization was 31.03% (range: 18.33%-38.95%) versus 22.91% (range: 16.55-32.15) in the RASPE group (P < 0.0001). Four weeks after the procedure, the liver volume increased by 28.98% (range: 9.31%-61.23%) in the PVE group and by 61.18% (range: 23.18%-201.56%) in the RASPE group (P < 0.0001). Seven patients in the PVE group, but none in the RASPE group, had postoperative liver failure (P = 0.012). CONCLUSIONS: RASPE can be considered as "radiological associating liver partition and portal vein ligation for staged hepatectomy." RASPE induced safe and profound growth of the FLR and was more efficient than PVE. RASPE also allowed for extended hepatectomy with less risk of post-operative liver failure.

Safety of trastuzumab after trastuzumab emtansine-induced nodular regenerative hyperplasia: A case report.

INTRODUCTION: Trastuzumab emtansine is an antibody-drug conjugate targeting the human epidermal growth factor receptor 2 use in recurrent metastatic breast cancer. Cases of trastuzumab emtansine-induced nodular regenerative hyperplasia are often reported as overt noncirrhotic portal hypertension with ascites and variceal bleeding. CASE REPORT: We report the case of a 61-year-old woman who present multiple stellate angiomas with gradual increased liver transaminases and reduced platelet count during a 27-months course on trastuzumab emtansine therapy for recurrent metastatic breast cancer. After the nodular regenerative hyperplasia was histologically confirmed, the trastuzumab emtansine was stopped. After two months, trastuzumab was restarted together with exemestane. During trastuzumab therapy, the patient had a normalization of liver transaminases, platelet count and a gradual improvement of her stellate angiomas. Trastuzumab was continued for 15 months without any reoccurrence of nodular regenerative hyperplasia. MANAGEMENT AND OUTCOME: Nodular regenerative hyperplasia should be suspected after one year of trastuzumab emtansine treatment in patients with signs of portal hypertension without cirrhosis. Definitive cessation of trastuzumab emtansine is required after a diagnosis of nodular regenerative hyperplasia and complete resolution of symptoms generally takes several months. DISCUSSION: Based on fundamental studies, nodular regenerative hyperplasia is probably caused by the emtansine (DM1) part of the trastuzumab emtansine. It is still unclear if trastuzumab therapy can be reintroduced after nodular regenerative hyperplasia induced by trastuzumab emtansine, depriving the patient of a HER2-targeted therapy. Only one case reported having given trastuzumab in this situation over one month. In our case, trastuzumab was reintroduced without any complications for a long extent following TDM1-associated nodular regenerative hyperplasia.

Very high-dose methylprednisolone for treatment of nivolumab-induced limbic encephalitis: A case report.

INTRODUCTION: Nivolumab is a programmed death 1 (PD-1) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of eight different cancers including metastatic melanoma. Immune checkpoint blockade may lead to a range of neurologic immune-related adverse events (irAEs) with severity varying from mild to life-threatening, including encephalitis. CASE REPORT: We describe a case of a 68-year-old man who developed alteration in mental status, physical weakness and fatigue after nine cycles of nivolumab 3 mg/kg every two weeks. These symptoms were compatible with a clinical diagnosis of autoimmune limbic encephalitis, although no specific antibodies were detected and the initial MRI was normal. MANAGEMENT AND OUTCOME: The patient received intravenous methylprednisolone 1 g daily for 5 days, which was then converted to a maintenance dose of oral prednisone. The patient made a full clinical recovery but relapsed clinically upon steroid tapering, while hypersignal in the left mesial temporal suggestive of limbic encephalitis was observed on repeated MRI. DISCUSSION: Because of the prevailing usage of nivolumab in many cancer protocols, this case highlights the importance of rapidly recognising neurological impairment in patients treated with nivolumab and of initiating very high doses of corticosteroids.

Toxic epidermal necrolysis associated with pembrolizumab.

INTRODUCTION: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous drug eruptions characterized by epidermal detachment. Pembrolizumab is a monoclonal antibody that binds to the programmed death-1 receptor, and it has been associated with numerous cutaneous adverse side-effects, including Stevens-Johnson syndrome. CASE REPORT: We describe a 63-year-old male with metastatic lung adenocarcinoma who developed a rapidly progressing maculopapular rash three days after a first dose of pembrolizumab. On day 16, the rash affected more than 80% of body surface area with detachment of large sheets of necrolytic epidermis in 30-40% of body surface area. However, the patient only presented with mild mucosal involvement. Histopathologic examination of a skin biopsy showed a subepidermal blister with overlying prominent full thickness epidermal keratinocytic necrosis and a superficial perivascular infiltrate of lymphocytes. A toxic epidermal necrolysis secondary to pembrolizumab was then diagnosed. Management and outcome: In addition to supportive cares, the patient received corticosteroids and cyclosporine. The patient responded rapidly to the immunosuppressant therapy, and nearly complete re-epithelialization was achieved 24 days after the start of the reaction. DISCUSSION: In our review of the literature, 15 other cases of Stevens-Johnson syndrome/toxic epidermal necrolysis were reported with programmed death-1/programmed cell death ligand-1 inhibitors. To our knowledge, this is the first case of toxic epidermal necrolysis secondary to pembrolizumab published in the literature. The American Society of Clinical Oncology guidelines suggest that cyclosporine, in addition to corticosteroids, be initiated when toxic epidermal necrolysis is suspected. Clinicians should be aware of this rare dermatological emergency with the increasing use of pembrolizumab in oncology.

Durable complete remission following anti-EGFR antibodies in recurrent metastatic colorectal cancer.

In this case report, we describe a patient who remains in complete remission two years after the discontinuation of anti-EGFR monotherapy as a third-line treatment, accompanied by persistent severe hypomagnesemia. A 45-year-old Caucasian woman with mCRC started chemotherapy with weekly cetuximab. After ten months of treatment, the therapy was stopped because the patient had persistent grade III hypomagnesemia despite amiloride, oral, and intravenous magnesium. A month later, the patient was switched to panitumumab 6 mg/kg every two weeks for four additional months to avoid weekly visits to the clinic. Following discontinuation of panitumumab, PET scans remain negative to this day, two years after anti-EGFR therapy discontinuation. No factor has been identified to explain the complete and sustained response experienced by this patient. Hypomagnesemia is a common adverse effect of anti-EGFR therapy that can lead to treatment interruption and discontinuation if severe. This case highlights the importance of pursuing anti-EGFR therapy when a response is observed in spite of severe hypomagnesemia. It also provides preliminary information that anti-EGFR therapy could be stopped after a complete response is obtained.