Factors of oncological failure in two stage hepatectomy for colorectal liver metastases.

BACKGROUND: Two-stage hepatectomy (TSH) has increased the chance of surgical resections for bilobar colorectal liver metastases (CRLM). Nevertheless, drop-out between stages and early recurrence rates raise the question of surgical futility in some situations. This study aimed to identify factors of TSH oncological failure. METHODS: Patients with bilobar CRLM eligible for TSH in three tertiary centers between 2010 and 2021 were included, and divided in Failure and Success groups. Oncological failure was defined as failure of the second stage hepatectomy for tumor progression or recurrence within 6 months after resection. RESULTS: Among 95 patients, 18 (18.9%) had hepatic progression between the two stages, and 7 (7.4%) failed to complete the second stage hepatectomy. After TSH, 31 (32.6%) patients experienced early recurrence. Overall, 38 (40.0%) patients experienced oncological failure (Failure group). The Failure group had lower median DFS (3 vs. 32 months, p < 0.001) and median OS (29 vs. 70 months, p = 0.045) than the Success group. On multivariable analysis, progression between the two stages in the future liver remnant (OR = 15.0 (3.22-113.0), p = 0.002), and maximal tumor size ≥40 mm in the future liver remnant (OR = 13.1 (2.12-117.0), p = 0.009) were independent factors of oncological failure. CONCLUSION: Recurrence between the two stages and maximal tumor size ≥40 mm in the future liver remnant were associated with TSH failure for patients with bilobar CRLM.

Preoperative Endoscopic Ultrasound-Guided Hepaticogastrostomy for Definite Biliary Drainage in Hilar Cholangiocarcinoma Laparoscopic Resection: A Hybrid Minimal-Invasive Technique.

BACKGROUND AND STUDY AIMS: Laparoscopic approach of perihilar cholangiocarcinoma (PHC) is still challenging. We report the original use of a endoscopic hepaticogastrostomy (EHG) for definite biliary drainage in order to avoid biliary reconstruction. PATIENTS AND METHODS: A 70-year-old man presenting with jaundice was referred for resection of a Bismuth type IIIa PHC. Repeated endoscopic retrograde cholangiopancreatography failed to drain the future liver remnant, enabling only right anterior liver section drainage. EHG was performed three weeks before surgery. A hepatogastric anastomosis was created, placing a half-coated self-expanding endoprosthesis between biliary duct of segment 2 and the lesser gastric curvature. RESULTS: A laparoscopic right hepatectomy extended to segment 1, common bile duct, and hepatic pedicle lymphadenectomy was performed. The left hepatic duct was sectioned and ligated downstream to the biliary confluence of segment 2-3 and 4 allowing exclusive biliary flow through the EHG. The patient was disease free at 12 months, postoperative outcomes were uneventful except three readmissions for acute cholangitis due to prosthesis obstruction. CONCLUSIONS: EHG may be used as definite biliary drainage technique in laparoscopic PHC resection, at the expense of prosthesis obstruction and cholangitis.

Modified Appleby procedure for locally advanced pancreatic carcinoma: A primer for the radiologist.

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent pancreatic neoplasm accounting for more than 90% of pancreatic malignancies. Surgical resection with adequate lymphadenectomy remains the only available curative strategy for patients with PDAC. Despite improvements in both chemotherapy regimen and surgical care, body/neck PDAC still conveys a poor prognosis because of the vicinity of major vascular structures, including celiac trunk, which favors insidious disease spread at the time of diagnosis. Body/neck PDAC involving the celiac trunk is considered locally advanced PDAC in most guidelines and therefore not eligible for upfront resection. However, a more aggressive surgical approach (i.e., distal pancreatectomy with splenectomy and en-bloc celiac trunk resection [DP-CAR]) was recently proposed to offer hope for cure in selected patients with locally advanced body/neck PDAC responsive to induction therapy at the cost of higher morbidity. The so-called "modified Appleby procedure" is highly demanding and requires optimal preoperative staging as well as appropriate patient preparation for surgery (i.e., preoperative arterial embolization). Herein, we review current evidence regarding DP-CAR indications and outcomes as well as the critical role of diagnostic and interventional radiology in patient preparation before DP-CAR, and early identification and management of DP-CAR complications.

Assessing textbook outcome after single large hepatocellular carcinoma resection.

BACKGROUND: This study aimed to investigate the impact and predictors of an ideal surgical care following SLHCC resection. METHODS: SLHCC patients who underwent LR in two tertiary hepatobiliary centers between 2000 and 2021 were retrieved from prospectively maintained databases. The quality of surgical care was measured by the textbook outcome (TO). Tumor burden was defined by the tumor burden score (TBS). Factors associated with TO were determined on multivariate analysis. The impact of TO on oncological outcomes was assessed using Cox regressions. RESULTS: Overall, 103 SLHCC patients were included. Laparoscopic approach was considered in 65 (63.1%) patients and 79 (76.7%) patients presented with moderate TBS. TO was achieved in 54 (52.4%) patients. Laparoscopic approach was independently associated with TO (OR 2.57; 95% CI 1.03-6.64; p = 0.045). Within 19 (6-38) months of median follow up, patients who achieved TO had better OS compared to non-TO patients (1-year OS: 91.7% vs. 66.9%; 5-year OS: 83.4% vs. 37.0%, p < 0.0001). On multivariate analysis, TO was independently associated with improved OS, especially in non-cirrhotic patients (HR 0.11; 95% CI 0.02-0.52, p = 0.005). CONCLUSIONS: TO achievement could be a relevant surrogate marker of improved oncological care following SLHCC resection in non-cirrhotic patients.

FCH-PET/CT in Primary Hyperparathyroidism With Discordant/Negative MIBI Scintigraphy and Ultrasonography.

CONTEXT: The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown. OBJECTIVE: To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX). DESIGN: Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism. SETTING: Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism. PATIENTS: Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX. MAIN OUTCOME MEASURES: To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT. RESULTS: The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients. CONCLUSION: This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon.

Safety and Feasibility of High-Pressure/High-Dose Pressurized Intraperitoneal Aerosol Chemotherapy (HP/HD-PIPAC) for Primary and Metastatic Peritoneal Surface Malignancies.

OBJECTIVE: The aim of this study was to evaluate the feasibility and perioperative safety of high-pressure/high-dose pressurized intraperitoneal aerosol chemotherapy (HP/HD-PIPAC) to manage peritoneal surface malignancies (PSM). METHODS: Retrospective analysis of a prospective database of about 130 consecutive patients scheduled for HP/HD-PIPACs for PSM. Doxorubicin plus cisplatin (PIPAC-C/D) or oxaliplatin (PIPAC-Ox) were nebulized into a constant capnoperitoneum of 20 mmHg at doses of 6, 30, or 120 mg/m2 of body surface area (BSA). Outcome criteria were perioperative complications (Clavien-Dindo). RESULTS: The median age of patients was 62 years (range 9-82), and the primary tumor site was of colorectal (CRC), upper gastrointestinal tract (UGI), unknown primary (CUP), malignant epithelioid mesothelioma of the peritoneum (MPM), hepato-pancreatic-biliary tract (HPB), and other origin in 30 (23.1%), 27 (20.8%), 16 (12.3%), 16 (12.3%), 6 (4.6%), and 35 (26.9%) patients, respectively. Abdominal access failed for a first, second, third, and fourth or more HP/HD-PIPAC in 12/130 (9.2%), 4/64 (6.3%), 6/40 (15.0%), and 2/33 (6.1%) patients. A total of 243 procedures were performed in 118 patients. No intraoperative complications related to increased capnoperitoneal pressure occurred, but an intraoperative bleeding complication was observed in 1/243 (0.4%) patients. The overall rate of postoperative procedure-related complications was 19.3% (47/243), while 15.3% (37/243), 1.6% (6/243), 1.6% (1/243), 0.4% (1/243), and 0.4% (1/243) were Grade I, II, III, IV, and V complications, respectively. CONCLUSIONS: Perioperative complications of HP/HD-PIPAC are comparable with standard pressure/dose PIPAC treatment protocols. Prospective studies are warranted to examine potential improvement in therapy outcomes.

Factors of Early Recurrence After Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Two-thirds of patients undergoing liver resection for intrahepatic cholangiocarcinoma experience recurrence after surgery. Our aim was to identify factors associated with early recurrence after resection for intrahepatic cholangiocarcinoma. METHODS: Patients with intrahepatic cholangiocarcinoma undergoing curative intent resection (complete resection and lymphadenectomy) were included in two centers between 2005 and 2021 and were divided into three groups: early recurrence (< 12 months after resection), delayed recurrence (> 12 months), and no recurrence. Patients experiencing early (< 90 days) postoperative mortality were excluded. RESULTS: Among 120 included patients, 44 (36.7%) experienced early recurrence, 24 (20.0%) experienced delayed recurrence, and 52 (43.3%) did not experience recurrence after a median follow-up of 59 months (IQR: 26-113). The median recurrence-free survival was 16 months (95% CI: 9.6-22.4). Median overall survival was 55 months (95% CI: 45.7-64.3), while it was 25 months for patients with early recurrence (p < 0.001). Patients with early recurrence had significantly larger tumors (59.1% of tumors > 70 mm in early vs. 58.3% in delayed vs. 26.9% in no recurrence group, p = 0.002), multiple lesions (65.9% vs. 29.2% vs. 11.5%, p < 0.001), and positive lymph nodes (N +) (38.6% vs. 37.5% vs. 11.5%, p = 0.005). In multivariable analysis, presence of multiple lesions (OR: 9.324; 95% CI: 3.051-28.489; p < 0.001) and positive lymph nodes (OR: 3.307. 95% CI: 1.001-11.011. p = 0.05) were associated with early recurrence. CONCLUSION: Early recurrence after curative resection of intrahepatic cholangiocarcinoma is frequent and is associated with the presence of multiple lesions and positive lymph nodes, raising the question of surgery's futility in this context.

Simultaneous or staged resection for synchronous liver metastasis and primary rectal cancer: a propensity score matching analysis.

BACKGROUND: Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15-25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. METHODS: We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. RESULTS: There were 70 patients (55/15 males, female respectively) with median age 60 (54-68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). CONCLUSIONS: Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

Impact of Modern Management Strategies on the Clinical Outcome of Patients With Low Rectal Cancer - A Retrospective, Monocentric Cohort Study.

BACKGROUND: The aim of this study was to retrospectively investigate the impact of intersphincteric resection (ISR) and Enhanced Recovery After Surgery (ERAS) protocols for rectal cancer. PATIENTS AND METHODS: Since we implemented rectal ERAS protocol and ISR in 2016, we retrospectively assessed and compared clinical, pathological and survival outcomes of two groups of patients: group 1, treated 2000-2015 (n=242); and group 2, treated 2016-2020 (n=108). Propensity score matching using nearest-neighbor method was used to match each patient of group 1 to a patient of group 2. RESULTS: Before and after matching, the American Society of Anesthesiology score for patients in group 1 was significantly lower than in group 2 (score of 3: 9.9% vs. 25.9%, p<0.0001) as were grade I-II complications (27.7% vs. 45.4% p<0.001). Before and after matching, the quality of the mesorectum excision was significantly lower in group 1 (complete in 31% vs. 59.2% p<0.0001). After matching, 3-year overall survival for groups 1 and 2 were similar (88.2% vs. 92.6%; p=0.988). CONCLUSION: ERAS and ISR had no negative impact on the oncological outcome of our patients and increased the preservation of bowel continuity.

Perihilar cholangiocarcinoma: What the radiologist needs to know.

Perihilar cholangiocarcinoma (PHC) is a common and highly intractable malignancy of the main biliary tree confluence. PHC is associated with a poor prognosis because of its insidious local spread that makes it challenging to diagnose and assess. Surgical resection remains the standard curative treatment (up to 50% 5-year overall survival after negative-margin resection). More aggressive surgical approaches have recently emerged, pushing the boundaries of PHC resectability at the cost of a higher morbidity. As such, adequate preoperative preparation (i.e., biliary drainage, venous embolization) is now regarded as a critical issue to increase the number of patients amenable to extended liver resection. Thorough imaging plays a pivotal role in the preoperative setting in both PHC resectability assessment and patient preparation to surgery. Despite recent improvement in PHC imaging, its assessment remains challenging and only 50-60% of patients who are scheduled to undergo surgery are ultimately amenable to curative resection. Therefore, a knowledge of available diagnostic and interventional imaging techniques is important to improve PHC management. Herein, we review the various imaging techniques and preoperative radiological interventions such as biliary drainage, portal vein embolization and liver venous deprivation that are available in PHC management focusing on the anatomical and oncological considerations that are crucial to prepare and guide curative surgical resection.

Predictors of discharge timing and unplanned readmission after laparoscopic liver resection.

BACKGROUND: The aim of the study was to determine the predictors of discharge timing and 90-day unplanned readmission after laparoscopic liver resection (LLR). METHODS: Consecutive LLR performed at the "Institut Mutualiste Montsouris" between 2000 and 2019 were retrieved from a prospectively maintained database. Length of stay (LOS) was stratified according to surgical difficulty and was categorized as early (LOS<25th percentile), routine (25th percentile<75th percentile), and delayed discharge otherwise. Uni-and-multivariate analyses were conducted to determine the factors associated with the time of discharge and 90-day unplanned readmission. RESULTS: Early discharge occurred in 15.7% patients whereas delayed discharge occurred in 20.6% patients. Concomitant pancreatic resections (OR 26.8, 95% CI 5.75-125, p < 0.0001) and removal of colorectal primary tumors (OR 7.14, 95% CI 3.98-12.8, p < 0.0001) were the strongest predictors of delayed discharge whereas ERP implementation was the strongest predictor of early discharge (OR 7.4, 95% CI 4.60-11.9, p < 0.0001). Unplanned readmission rate was lower among early discharged patients (7.4% vs. 23.8%, p < 0.0001). Bile leakage was the strongest predictor of 90-day unplanned readmission (OR 3.8, 95% CI 1.12-15.8, p = 0.045). CONCLUSION: Concomitant colorectal or pancreatic resections were the strongest predictors of delayed discharge. Postoperative bile leakage was the strongest predictor of 90-day unplanned readmission following LLR.

Clinical Outcome for Patients Managed with Low-Dose Cisplatin and Doxorubicin Delivered as Pressurized Intraperitoneal Aerosol Chemotherapy for Unresectable Peritoneal Metastases of Gastric Cancer.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to manage gastric cancer peritoneal metastasis (GCPM). METHODS: This study analyzed a prospective database of GCPM patients treated with cisplatin and doxorubicin PIPAC (PIPAC-C/D). The outcome criteria were adverse events, pathologic response [peritoneal regression grading score (PRGS)], and overall survival (OS). RESULTS: The PIPAC-C/D procedure was scheduled for 144 patients with a median age of 57 years (range 22-88 years). Access to the abdominal cavity for the first PIPAC failed in 11 patients (7.7 %). A total of 296 procedures were performed for 131 patients. Of the 144 patients, 52 (36.1%) underwent one PIPAC, 32 (22.2%) underwent two PIPACs, 24 (16.7%) underwent three PIPACs, and 21 (14.6%) underwent four or more PIPACs. The overall morbidity/mortality was grade 1 for 22 patients (15.3%), grade 2 for 32 patients (22.2%), grade 3 for 7 patients (4.9%), grade 4 for no patients (0%), and grade 5 for 2 patients (1.4%). Of the 37 patients who had three or more PIPACs eligible for histopathologic response analysis, 27 (73%) had major or complete regression (PRGS 1/2). A median OS of 11 months (range 0-61 months) for the total study population and 16 months (range 2-61 months) for the patients with three or more PIPACs was observed. For 10 patients (7%) who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, the median OS was 15 months (minimum, 4 months; maximum, 27 months). Multivariate analysis showed three or more PIPACs to be an independent prognostic factor for improved OS (hazard ratio, 0.36; p < 0.0001). CONCLUSIONS: Repetitive PIPAC-C/D ± systemic chemotherapy is associated with low morbidity and mortality rates. Prospective randomized trials are needed to confirm whether three or more PIPAC-C/Ds improve clinical outcome.

Prognostic Impact of Upfront Surgery for Locally Advanced Upper Rectal Adenocarcinoma.

BACKGROUND/AIM: Impact of neoadjuvant chemoradiotherapy (CRT) in locally advanced upper rectal adenocarcinoma (LAURC) is debated. The aim of this study was to compare outcomes between LAURC and locally advanced sigmoid and recto-sigmoid junction cancer (LASC). PATIENTS AND METHODS: This retrospective study included 149 consecutive patients [42 CRT/LAURC, 16 upfront surgery (US/LAURC) and 91 LASC]. Partial mesorectum excision (PME) was performed for all LAURC. Pathology results as well as short-and-long-term outcomes were compared between the three groups. RESULTS: Overall mortality was nil. Morbidity was comparable (CRT/LAURC 23.8% vs. LASC: 20.8% vs. US/LAURC: 37.5%, p=0.2354). CRT was associated with a reduced risk of positive circumferential margin (CRT/LAURC: 9.5% vs. US/LAURC: 18.7%, p<0.0001). Recurrence rate, 5-year disease-free survival and overall survival were similar between the three groups. CONCLUSION: CRT and PME did not improve LAURC oncological outcomes but were associated with improved margins. CRT for LAURC was not associated with increased morbidity.

Endogenous Interleukin-33 Acts as an Alarmin in Liver Ischemia-Reperfusion and Is Associated With Injury After Human Liver Transplantation.

Ischemia and reperfusion injury is an early inflammatory process during liver transplantation that impacts on graft function and clinical outcomes. Interleukin (IL)-33 is a danger-associated molecular pattern involved in kidney ischemia/reperfusion injury and several liver diseases. The aims were to assess whether IL-33 was released as an alarmin responsible for ischemia/reperfusion injury in a mouse model of warm hepatic ischemia, and whether this hypothesis could also apply in the setting of human liver transplantation. First, a model of warm hepatic ischemia/reperfusion was used in wild-type and IL-33-deficient mice. Severity of ischemia/reperfusion injury was assessed with ALT and histological analysis. Then, serum IL-33 was measured in a pilot cohort of 40 liver transplant patients. Hemodynamic postreperfusion syndrome, graft dysfunction (assessed by model for early allograft scoring >6), renal failure, and tissue lesions on time-zero biopsies were assessed. In the mouse model, IL-33 was constitutively expressed in the nucleus of endothelial cells, immediately released in response to hepatic pedicle clamping without neosynthesis, and participated in the recruitment of neutrophils and tissue injury on site. The kinetics of IL-33 in liver transplant patients strikingly matched the ones in the animal model, as attested by serum levels reaching a peak immediately after reperfusion, which correlated to clinical outcomes including postreperfusion syndrome, posttransplant renal failure, graft dysfunction, and histological lesions of ischemia/reperfusion injury. IL-33 was an independent factor of graft dysfunction with a cutoff of IL-33 at 73 pg/ml after reperfusion (73% sensitivity, area under the curve of 0.76). Taken together, these findings establish the immediate implication of IL-33 acting as an alarmin in liver I/R injury and provide evidence of its close association with cardinal features of early liver injury-associated disorders in LT patients.

Surgical management of pancreatic neuroendocrine tumors: an introduction.

Introduction: Neuroendocrine tumors of the pancreas (pNETs) represent only 1% to 2% of all pancreatic neoplasms. These tumors can be classified as functional or nonfunctional tumors; as sporadic or from a genetic origin; as neuroendocrine neoplasms or carcinoma. Over the last decade, diagnosis of pNETs has increased significantly mainly due to the widespread use of cross-sectional imaging. Those tumors are usually associated with a good prognosis. Surgery, the only curative option for those patients, should always be discussed, ideally in a multidisciplinary team setting.Areas covered: We discuss i), the preoperative management of pNETs and the importance of accurate diagnosis, localization, grading and staging with computed tomography, magnetic resonance imaging, endoscopic ultrasound, and nuclear medicine imaging; ii), surgical indications and iii), the surgical approach (standard pancreatectomy vs pancreatic-sparing surgery).Expert opinion: The treatment option of all patients presenting with pNETs should be discussed in a multidisciplinary team setting with surgeon's experienced in both pancreatic surgery and neuroendocrine tumor management. A complete preoperative imaging assessment - morphological and functional - must be performed. Surgery is usually recommended for functional pNETs, nonfunctional pNETs >2 cm (nf-pNETs) or for symptomatic nf-pNETs.

Robot-Assisted Total Gastrectomy: Preliminary Evaluation.

Background: Laparoscopic total gastrectomy with extended lymphadenectomy is a technically demanding surgical procedure with steep learning curve that has limited its widespread use. The aim of this study was to evaluate the feasibility of the robotic approach in total gastrectomy for cancer. We present our experience of 17 consecutive patients who underwent robotic total gastrectomy with intracorporal sutured Roux-en-Y esophagojejunostomy and jejuno jejunostomy between 2014 and 2017. Methods: Data were collected, and patients' demographics and outcomes were examined retrospectively. Results: Seventeen patients with a median age of 68 years (range 32-81) were identified (10 males, 7 females). Mean operative time was 198 minutes (range 108-277) including mean anastomosis time of 25 minutes (range 18-35). There was no conversion to open surgery or requirement for perioperative blood transfusion. Median length of hospital stay was 9 days (range 2-30). Two patients developed postoperative complications including one anastomotic leakage treated conservatively and one internal hernia requiring surgical revision. There was no 90-day mortality or readmission. Conclusion: Robot-assisted total gastrectomy is feasible and reproducible. It overcomes several laparoscopic technical difficulties especially regarding anastomosis. It has the potential to become an alternative to open gastrectomy for gastric cancer. Nevertheless, further follow-up and randomized clinical trials are needed to evaluate mid-term and long-term outcomes of this approach.