The Impact of Portal Hypertension Assessment Method on the Outcomes of Hepatocellular Carcinoma Resection: A Meta-Analysis of Matched Cohort and Prospective Studies.

OBJECTIVE: Examine portal hypertension (PHT) impact on postoperative and survival outcomes in hepatocellular carcinoma (HCC) patients after liver resection (LR), specifically exploring distinctions between indirect signs and invasive measurements of PHT. BACKGROUND: PHT has historically discouraged LR in individuals with HCC due to the elevated risk of morbidity, including liver decompensation (LD). METHODS: A systematic review was conducted using 3 databases to identify prospective-controlled and matched cohort studies until December 28, 2022. Focus on comparing postoperative outcomes (mortality, morbidity, and liver-related complications) and overall survival in HCC patients with and without PHT undergoing LR. Three meta-analysis models were utilized: for aggregated data (fixed-effects inverse variance model), for patient-level survival data (one-stage frequentist meta-analysis with gamma-shared frailty Cox proportional hazards model), and for pooled data (Freeman-Tukey exact and double arcsine method). RESULTS: Nine studies involving 1124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with hepatic venous pressure gradient (HVPG) ≥10 mm Hg significantly increased the risk of overall complications, PHLF, and LD. Despite elevated risks, the procedure resulted in a 5-year overall survival rate of 55.2%. Open LR significantly increased the risk of overall complications, PHLF, and LD. Conversely, PHT did not show a significant association with worse postoperative outcomes in minimally invasive LR. CONCLUSIONS: LR in the presence of indirect signs of PHT poses no increased risk of complications. Yet, in HVPG ≥10 mm Hg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions. Minimally invasive approach seems to be vital for favorable outcomes, especially in HVPG ≥10 mm Hg patients.

Tailoring the Use of Central Pancreatectomy Through Prediction Models for Major Morbidity and Postoperative Diabetes: International Retrospective Multicenter Study.

OBJECTIVE: To develop a prediction model for major morbidity and endocrine dysfunction after CP which could help in tailoring the use of this procedure. SUMMARY BACKGROUND DATA: Central pancreatectomy (CP) is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and pre-malignant tumors in body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared to distal pancreatectomy but it is thought to increase the risk of short-term complications including postoperative pancreatic fistula (POPF). METHODS: International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010-2021). Primary endpoint was major morbidity. Secondary endpoints included POPF grade B/C, endocrine dysfunction, and the use of pancreatic enzymes. Two risk model were designed for major morbidity and endocrine dysfunction utilizing multivariable logistic regression and internal and external validation. RESULTS: 838 patients after CP were included (301 (36%) minimally invasive) and major morbidity occurred in 248 (30%) patients, POPF B/C in 365 (44%), and 30-day mortality in 4 (1%). Endocrine dysfunction in 91 patients (11%) and use of pancreatic enzymes in 108 (12%). The risk model for major morbidity included male sex, age, BMI, and ASA score≥3. The model performed acceptable with an area under curve (AUC) of 0.72(CI:0.68-0.76). The risk model for endocrine dysfunction included higher BMI and male sex and performed well (AUC:0.83 (CI:0.77-0.89)). CONCLUSIONS: The proposed risk models help in tailoring the use of CP in patients with symptomatic benign and premalignant lesions in the body and neck of the pancreas and are readily available via www.pancreascalculator.com.

Association of Laparoscopic Surgery with Improved Perioperative and Survival Outcomes in Patients with Resectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis from Propensity-Score Matched Studies.

BACKGROUND: Recent studies have associated laparoscopic surgery with better overall survival (OS) in patients with hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). The potential benefits of laparoscopic liver resection (LLR) over open liver resection (OLR) have not been demonstrated in patients with intrahepatic cholangiocarcinoma (iCC). METHODS: A systematic review of the PubMed, EMBASE, and Web of Science databases was performed to search studies comparing OS and perioperative outcome for patients with resectable iCC. Propensity-score matched (PSM) studies published from database inception to May 1, 2022 were eligible. A frequentist, patient-level, one-stage meta-analysis was performed to analyze the differences in OS between LLR and OLR. Second, intraoperative, postoperative, and oncological outcomes were compared between the two approaches by using a random-effects DerSimonian-Laird model. RESULTS: Six PSM studies involving data from 1.042 patients (530 OLR vs. 512 LLR) were included. LLR in patients with resectable iCC was found to significantly decrease the hazard of death (stratified hazard ratio [HR]: 0.795 [95% confidence interval [CI]: 0.638-0.992]) compared with OLR. Moreover, LLR appears to be significantly associated with a decrease in intraoperative bleeding (- 161.47 ml [95% CI - 237.26 to - 85.69 ml]) and transfusion (OR = 0.41 [95% CI 0.26-0.69]), as well as with a shorter hospital stay (- 3.16 days [95% CI - 4.98 to - 1.34]) and a lower rate of major (Clavien-Dindo ≥III) complications (OR = 0.60 [95% CI 0.39-0.93]). CONCLUSIONS: This large meta-analysis of PSM studies shows that LLR in patients with resectable iCC is associated with improved perioperative outcomes and, being conservative, yields similar OS outcomes compared with OLR.

Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma.

BACKGROUND: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other tumors, but scarce data is available in pancreatic cancer. METHODS: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil (5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated. RESULTS: By exploratory univariate analyses, a significantly longer progression-free survival was observed for patients with either 5-FU area under the curve (AUC) above 28 mcg·h/mL or CPT-11 AUC values below 10 mcg·h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC ≥28 mcg·h/mL [HR = 0.251, 95% CI 0.096-0.656; p = 0.005] and CPT-11 AUC <10 mcg·h/mL [HR = 0.189, 95% CI 0.073-0.486, p = 0.001]. CONCLUSIONS: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might improve survival outcomes in patients with pancreatic ductal adenocarcinoma.

Delays to surgery following chemoradiotherapy lead to poorer oncologic outcomes in patients with localized pancreatic adenocarcinoma.

BACKGROUND: although neoadjuvant chemoradiotherapy (NCRT) and surgery are accepted as treatments for pancreatic ductal adenocarcinoma (PDAC), some authors have highlighted the risks of delaying surgery. The objective of this study was to analyze the impact of prolonging the time interval between NCRT and surgery (NCRT-TTS) in PDAC. METHODS: patients treated with NCRT and pancreatoduodenectomy (PD) were identified. Clinical, histopathological variables were analyzed about whether NCRT-TTS was greater or less than 50 days. Five- and ten-year overall survival (OS) and disease-free survival (DFS) were analyzed depending on whether the delay was greater than 50 days or not. RESULTS: one hundred (8.3 %) of 120 eligible patients underwent PD (61 male, median age of 63.7 years). In 71 (71 %) patients, the median NCRT-TTS was 39 (24-50) days and in 29 (29 %) 61 days. There were no differences between the two groups except for carbohydrate antigen 19-9 (CA 19-9) levels, the incidence of cholangitis, American Society of Anesthesiologists (ASA) score, intraoperative blood transfusions and degree of histopathologic response (all p < 0.001). Median DFS when the NCRT-TTS was less than 50 days was higher than when the interval exceeded 50 days (51.0 months [95 % CI: 20.3-81.6] vs 17.0 months [95 %: CI 10.9-23.0]; HR [95 % CI 1.08-3.46], p = 0.026). Five-year DFS was higher in the subgroup with NCRT-TTS of less than 50 days compared to the group with an interval of more than 50 days (43.5 % vs 23.65 % [HR 1.812, 95 % CI: 1.001-3.280], p = 0.050). CONCLUSIONS: an increase in the NCRT-TTS > 50 days is associated with poorer OS and DFS in patients with localized PDAC treated with NCRT and PD.

Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

Full Laparoscopic Vascular Reconstruction for Portal Tumoral Invasion During a Right Hepatectomy Using the Caudal Approach.

BACKGROUND: Laparoscopic liver surgery has progressively evolved. Consequently, liver procedures are increasingly performed laparoscopically, particularly in experienced centers. However, vascular resection and reconstruction still are considered a limitation for laparoscopy1 due to the risk of bleeding and the technical difficulty. METHODS: A 72-year-old woman with a history of colorectal cancer had a 10 cm metastasis diagnosed in the right hemiliver with tumoral invasion of the right portal branch and tumor thrombus advancing to the portal confluence. After adjuvant chemotherapy and with stable disease, surgical resection was planned.2,3 Tips to avoid portal stenosis were carefully followed. RESULTS: The operation was performed with a fully laparoscopic procedure. To minimize manipulation, an in situ right hepatectomy was performed.4 The right hepatic artery was dissected and ligated. The liver transection was guided with a caudal approach of the middle hepatic vein.5 The right biliary duct was then divided, achieving an excellent exposure of the portal bifurcation. The main and left portal trunks were occluded with vascular clamps, and the right portal vein was sharply divided with scissors. The stump was sutured to minimize backflow bleeding and to cover the tumor thrombus. Then, the portal opening was transversally sutured with a 5/0 running suture. The clamps were released, and the authors observed no bleeding and an adequate caliber with no stenosis. The procedure was completed in the standard fashion. The postoperative course was uneventful, and the woman was discharged on postoperative day 3. No early or late complications were observed.6 CONCLUSIONS: In selected cases, patients who require vascular resection and reconstruction during hepatectomies can benefit from the advantages of a laparoscopic approach.

Pure laparoscopic major liver resection after yttrium90 radioembolization: a case-matched series analysis of feasibility and outcomes.

BACKGROUND: Liver surgery after radioembolization (RE) entails highly demanding and challenging procedures due to the frequent combination of large tumors, severe RE-related adhesions, and the necessity of conducting major hepatectomies. Laparoscopic liver resection (LLR) and its associated advantages could provide benefits, as yet unreported, to these patients. The current study evaluated feasibility, morbidity, mortality, and survival outcomes for major laparoscopic liver resection after radioembolization. MATERIAL AND METHODS: In this retrospective, single-center study patients diagnosed with hepatocellular carcinoma, intrahepatic cholangiocarcinoma or metastases from colorectal cancer undergoing major laparoscopic hepatectomy after RE were identified from institutional databases. They were matched (1:2) on several pre-operative characteristics to a group of patients that underwent major LLR for the same malignancies during the same period but without previous RE. RESULTS: From March 2011 to November 2020, 9 patients underwent a major LLR after RE. No differences were observed in intraoperative blood loss (50 vs. 150 ml; p = 0.621), operative time (478 vs. 407 min; p = 0.135) or pedicle clamping time (90.5 vs 74 min; p = 0.133) between the post-RE LLR and the matched group. Similarly, no differences were observed on hospital stay (median 3 vs. 4 days; p = 0.300), Clavien-Dindo ≥ III complications (2 vs. 1 cases; p = 0.250), specific liver morbidity (1 vs. 1 case p = 1.000), or 90 day mortality (0 vs. 0; p = 1.000). CONCLUSION: The laparoscopic approach for post radioembolization patients may be a feasible and safe procedure with excellent surgical and oncological outcomes and meets the current standards for laparoscopic liver resections. Further studies with larger series are needed to confirm the results herein presented.

Neoadjuvant treatment in localized and resectable cancer of the pancreas: a new therapeutic paradigm.

Ductal carcinoma of the pancreas (DCP) is one of the most devastating tumors and ranks fourth among the causes of death from cancer. It is estimated that by 2030 it will be among the top three "cancer killers", along with lung cancer and hepatocarcinoma. Overall survival at five years from diagnosis is 5-10% in centers with experience. At the time of diagnosis, only 10-15% of patients present tumors localized to the pancreas and which are susceptible to curative resection (R0) (resectable tumors). Fifty percent present with systemic disease (stage IV) and 30-35% present borderline or locally advanced tumors which are generally not resectable due to vascular invasion.

Comparison of phenotypes and outcomes following resection of incidental versus symptomatic pancreatic neuroendocrine tumors.

BACKGROUND AND AIM: fifty to 70 percent of pancreatic neuroendocrine tumors are diagnosed incidentally. The objective of this study was to compare the phenotype and oncological outcomes of incidental versus symptomatic pancreatic neuroendocrine tumors. METHODS: a retrospective study was performed, identifying all incidental and symptomatic tumors resected between 2000 and 2019. Baseline characteristics, symptoms, operative variables and pathological stage were all recorded. Patterns of recurrence and overall and disease-free survival were analyzed in both groups. RESULTS: fifty-one incidental and 45 symptomatic pancreatic tumor resections were performed. Symptomatic tumors were more frequent in females (29 vs 17; p = 0.005) and younger patients (median years; 50 vs 58; p = 0.012) and were detected at a more advanced stage (p = 0.027). There were no differences in location and most resections (n = 49; 51 %) were performed laparoscopically. There were no operative mortalities and 17 (17.7 %) severe complications (≥ IIIb on the Clavien-Dindo classification) were recorded with no differences between the two groups. With a median follow-up of 64.4 months (range 13.5-90), overall survival at five and ten years was 89.7 % and 72.8 % for the non-incidental tumors and 80.9 % and 54.6 % for the incidental tumors (p = ns), respectively. Disease-free survival in both groups (excluding M1a) was 71.2 % and 47.5 %, and 93.7 % and 78.1 %, respectively (p = ns). CONCLUSIONS: symptomatic tumors are more frequent in females and present at more advanced pathological stages. There were no significant differences in overall and disease-free survival between the two groups. Resection of incidental tumors ≥ 1.5-2 cm seems advisable, although each case should be assessed on an individual basis.

Incidental lesions of the pancreas. A clinicopathological study of 100 cases surgically treated.

OBJECTIVE: the objective of the present study was to analyze the characteristics of resected incidental lesions of the pancreas. MATERIAL AND METHODS: a retrospective study was performed of pancreatectomies due to incidentalomas between 1995 and 2018. RESULTS: one hundred pancreatectomies were performed due to incidental lesions; 64 (64%) were solid and 36 (36%) were cystic lesions. The cytological analysis agreed with the diagnosis in 67/71 (88.7%) cases. Thirty-six tumors were cystic, 48 were neuroendocrine and 16 were adenocarcinomas. Disease-free survival for patients with cystic, neuroendocrine tumors and adenocarcinomas was 100%, 79% and 57.7% (p < 0.04). CONCLUSION: pancreatic incidentalomas have a heterogeneous phenotype and should be treated in experienced centers.

Severe colon ischemia in patients with severe coronavirus-19 (COVID-19).

COVID-19 is associated with severe coagulopathy. We present three cases of colonic ischemia that can be attributed to the hypercoagulable state related with SARS-CoV2 and disseminated intravascular coagulation. Three males aged 76, 68 and 56 with respiratory distress presented episodes of rectal bleeding, abdominal distension and signs of peritoneal irritation. Endoscopy (case 1) and computed tomography angiography revealed colonic ischemia. One patient (case 2) in which a computed tomography (CT) scan showed perforation of the gangrenous cecum underwent surgery. D-dimer levels were markedly increased (2,170, 2,100 and 7,360 ng/ml) in all three patients. All three patients died shortly after diagnosis.

Cystic tumors of the pancreas. An update of the surgical experience in a single institution.

BACKGROUND: the aim of the present study was to analyze the clinicopathological features of patients undergoing pancreatic surgical resections due to cystic neoplasms of the pancreas. MATERIAL AND METHODS: demographic data, form of presentation, radiologic images and location of the tumors within the pancreas were analyzed. Data was also collected on the type of surgery (open/laparoscopic), postoperative complications and their severity and oncologic outcomes. RESULTS: eighty-two pancreatic resections were performed. The mean age of patients was 57 years and 49 (59%) were female. Forty-one tumors (50%) were incidental and the most frequent symptoms in the group of symptomatic patients were abdominal pain (63.4%) and weight loss (36.5%). Thirty-two tumors (39%) were located in the tail of the pancreas, 25 (30.5%) in the head and 20 (24.4%) in the body. Thirty-nine (47.5%) distal pancreatectomies, 16 central, ten duodenal pancreatectomies and one enucleation were performed; 40 (48.5%) were carried out laparoscopically. Mean hospital stay was ten days and eight patients (7%) experienced severe complications, one was a pancreatic fistula. Sixty-six tumors (80.5%) were recorded as non-invasive and 16 (19.5%) as invasive: seven intraductal mucinous papillary tumors, one cystic mucinous tumor, four solid pseudopapillary tumors and four cystic neuroendocrine tumors. There was a median follow-up of 64 months; disease-free survival at five and ten years was 97.4% in the patients with non-invasive tumors and 84.6% and 70.5% in the invasive tumors group (p < 0.01). CONCLUSIONS: fifty percent of cystic neoplasms of the pancreas are incidental. Two phenotypes exist, invasive and non-invasive.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: clinicopathological features and long-term outcomes following a pancreatectomy.

OBJECTIVE: the objective of this study was to analyze the anatomical and clinical features and long-term oncologic outcomes of 25 patients that underwent surgery due to intraductal papillary mucinous neoplasm of the pancreas. MATERIAL AND METHODS: patients undergoing surgery for intraductal papillary mucinous neoplasm of the pancreas were identified from a prospective database of pancreatic resections. Demographic data, symptoms, type of surgery and type of lesion (branch type, main duct or mixed) were recorded. The lesions were classified into invasive (high grade dysplasia and carcinoma) and noninvasive (low- or intermediate-grade dysplasia). Postoperative complications were analyzed as well as the pattern of recurrence and disease-free survival at five and ten years. RESULTS: the most common symptoms in the 25 patients (14 males and eleven females) were abdominal pain and weight loss. Eight (32%) cases were diagnosed incidentally. Twelve (48%) of the lesions were of the branch type, three affected the main duct and ten (40%) were mixed. Twelve cephalic duodenopancreatectomies and seven total pancreatectomies were performed; three were central; two, distal; and one, enucleation. Seven cases (32%) had an invasive phenotype. Three patients had locoregional and distant recurrence at six, 16 and 46 months after surgery with a median follow-up of 7.7 years. Disease-free survival at five and ten years for the noninvasive type was 94% and 57% for invasive phenotypes (p < 0.05). CONCLUSIONS: intraductal papillary mucinous neoplasm is a heterogeneous entity with well differentiated phenotypes, which requires a tailored strategy and treatment, as established in the current consensus guidelines due to its malignant potential.

Clinico-pathological and oncological differences between right and left-sided colon cancer (stages I-III): analysis of 950 cases.

PURPOSE: The objective of the study was to analyze the clinico-pathological differences and the oncologic outcomes between right and left-sided colon cancer. PATIENTS AND METHODS: The patients cohort was identified from a prospective register of colon cancer, 950 patients underwent surgery (stages I, II and III), of which 431 had right-sided colon cancer and 519 had left-sided colon cancer. RESULTS: More laparoscopic resections were performed (101 vs 191; p < 0.001) and operating times were longer (146 min vs 165 min; p < 0.001) in the left-sided colon group. Patients with right-sided colon cancer more frequently received transfusions (18.8% vs 11.3%; p < 0.001) and experienced a greater number of complications (28.5% vs 20.9%, p = 0.004), although severity and operative mortality were similar in both groups (1.2% vs 0.2%). Mucinous adenocarcinomas and undifferentiated tumors were more frequent in the right-sided group (12% vs 6.5%; p < 0.001). Early stage was predominant in the left-sided colon tumors (28.2% vs 34.5%, p = 0.02). There were no differences in disease-free survival (DFS) in stages I and II after a median follow-up of 103 months. However, a greater survival at five and ten years in left-sided, stage III tumors was observed, with a trend towards statistical significance (p = 0.06). No differences were found with regard to the patterns of recurrence. CONCLUSIONS: Right-sided colon cancer exhibits phenotypical differences with regard to left-sided colon cancer. In stage III disease, left-sided colon cancer has a greater survival with a trend towards statistical significance. Overall, tumor location is a variable that should be taken into consideration in clinical studies of colon cancer.

Screening-detected colorectal cancers show better long-term survival compared with stage-matched symptomatic cancers.

PURPOSE: the aim of this study was to compare overall and disease-free survival among patients with colorectal cancer detected via a screening program as compared to those with symptomatic cancer. MATERIAL AND METHODS: patients diagnosed via colonoscopy (screening group) and those with clinical symptoms (non-screening) were identified from 1995 to 2014. Demographic, clinical, surgical and pathologic variables were recorded. Stage I, II and III cancers were included. Overall and disease-free survival were calculated at five and ten years after tumor resection and survival was calculated by matching both groups for cancers at stage I, II and III. RESULTS: two hundred and fifty patients were identified as a result of screening procedures and 1,330 patients presented with symptomatic cancers. There were no significant differences in the baseline characteristics between the two groups. Pathologic stage, degree of differentiation, perineural invasion and lymphovascular invasion were lower in the screening group (p < 0.01). Overall and disease-free survival at five and ten years were higher in the screening group (p < 0.01). However, when the subjects were matched for pathologic stage, significant differences were found between the two groups with regard to stage I and III tumors. Disease-free survival in stage III at five years (79.1 vs 61.7%; p < 0.001) and ten years (79.1% vs 58.5%; p < 0.001) were significantly higher in the screening group. CONCLUSIONS: patients with stage I and III tumors that were diagnosed via a screening program have a higher overall and disease-free survival at five and ten years.