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.

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 PHT impact on postoperative and survival outcomes in HCC patients after LR, specifically exploring distinctions between indirect signs and invasive measurements of PHT. SUMMARY BACKGROUND DATA: 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 OS 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 1,124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with HVPG ≥10 mmHg significantly increased the risk of overall complications, PHLF and LD. Despite elevated risks, the procedure resulted in a 5-year OS 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 MILR. CONCLUSIONS: LR with indirect PHT signs poses no increased risk of complications. Yet, in HVPG ≥10 mmHg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions. MI approach seems to be vital for favorable outcomes, especially in HVPG ≥10 mmHg patients.

Impact of perineural invasion on the outcome of patients with synchronous colorectal liver metastases treated with neoadjuvant chemotherapy and surgery

Purpose To analyze the prognostic value of variables of the primary tumor in patients with synchronous liver metastases in colorectal cancer (CLRMs) treated with neoadjuvant chemotherapy and surgery. Methods/Patients From a prospective database, we retrospectively identified all patients with synchronous CLRMs who were treated with neoadjuvant chemotherapy and liver resection. Using univariate and multivariate analyses, we identified the variables associated with tumor recurrence. Overall survival and disease-free survival were calculated using the Kaplan–Meier method with differences determined by the Cox multiple hazards model. Results were compared using the log-rank test. Results Ninety-eight patients with synchronous CLRMs were identified. With a median follow-up of 39.8 months, overall survival and disease-free survival at 5 and 10 years were 53%, 41.7%, 29% and 29%, respectively. Univariate analysis identified three variables associated with tumor recurrence: location in the colon (p = 0.025), lymphovascular invasion (p = 0.011) and perineural invasion (p = 0.005). Multivariate analysis identified two variables associated with worse overall survival: perineural invasion (HR 2.36, 95% CI 1.162–4.818, p = 0.018) and performing frontline colectomy (HR 3.286, 95% CI 1.256–8.597, p = 0.015). Perineural invasion remained as the only variable associated with lower disease-free survival (HR 1.867, 95% CI 1.013–3.441, p = 0.045). Overall survival at 5 and 10 years in patients with and without perineural invasion was 68.2%, 54.4% and 29.9% and 21.3%, respectively (HR 5.920, 95% CI 2.241–15.630, p < 0.001). Conclusions Perineural invasion in the primary tumor is the variable with most impact on survival in patients with synchronous CLRMs treated with neoadjuvant chemotherapy and surgery (AU)

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.

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.

Impact of perineural invasion on the outcome of patients with synchronous colorectal liver metastases treated with neoadjuvant chemotherapy and surgery.

PURPOSE: To analyze the prognostic value of variables of the primary tumor in patients with synchronous liver metastases in colorectal cancer (CLRMs) treated with neoadjuvant chemotherapy and surgery. METHODS/PATIENTS: From a prospective database, we retrospectively identified all patients with synchronous CLRMs who were treated with neoadjuvant chemotherapy and liver resection. Using univariate and multivariate analyses, we identified the variables associated with tumor recurrence. Overall survival and disease-free survival were calculated using the Kaplan-Meier method with differences determined by the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: Ninety-eight patients with synchronous CLRMs were identified. With a median follow-up of 39.8 months, overall survival and disease-free survival at 5 and 10 years were 53%, 41.7%, 29% and 29%, respectively. Univariate analysis identified three variables associated with tumor recurrence: location in the colon (p = 0.025), lymphovascular invasion (p = 0.011) and perineural invasion (p = 0.005). Multivariate analysis identified two variables associated with worse overall survival: perineural invasion (HR 2.36, 95% CI 1.162-4.818, p = 0.018) and performing frontline colectomy (HR 3.286, 95% CI 1.256-8.597, p = 0.015). Perineural invasion remained as the only variable associated with lower disease-free survival (HR 1.867, 95% CI 1.013-3.441, p = 0.045). Overall survival at 5 and 10 years in patients with and without perineural invasion was 68.2%, 54.4% and 29.9% and 21.3%, respectively (HR 5.920, 95% CI 2.241-15.630, p < 0.001). CONCLUSIONS: Perineural invasion in the primary tumor is the variable with most impact on survival in patients with synchronous CLRMs treated with neoadjuvant chemotherapy and surgery.

Liver Resection and Transplantation Following Yttrium-90 Radioembolization for Primary Malignant Liver Tumors: A 15-Year Single-Center Experience.

Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. METHODS: Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. RESULTS: A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. CONCLUSION: Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.

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.

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 (AU)

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.

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. (AU)

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.