Curative-intent Resection Research Articles

Immune checkpoint inhibitors in hepatocellular carcinoma: Areview of current clinical trials.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis due to advanced disease presentation or recurrence despite curative-intent resection. Since the approval of sorafenib in 2007, few systemic therapies offered a significant improvement in treatment outcomes. Over the last 3 years, however, rapid advancements in the field of immunotherapy have led to approval of checkpoint inhibitors in 2020 for use in advanced HCC. Since then, a few other clinical trials have shown promising results in the adjuvant and neoadjuvant setting. The objective of this review is to summarize data from existing clinical trials evaluating the use of systemic immune checkpoint inhibitors in HCC and to follow the natural evolution of this development across the metastatic, adjuvant, and neoadjuvant landscapes.

Evaluation of optimum classification measures used to define textbook outcome among patients undergoing curative-intent resection of gastric cancer

BackgroundTextbook outcome (TO) is a composite measure reflecting various aspects of services provided to patients with solid malignancies. We sought to evaluate the importance of various TO components previously proposed for gastric cancer.MethodsProspectively maintained electronic databases of 1,743 patients treated in two academic surgical centres were reviewed. Six candidate definitions of TO were evaluated based on their ability to accurately predict patients’ prognosis by Cox proportional hazards modelling.ResultsTO definition combining 10 measures corresponding to complete tumour resection with an uneventful postoperative course showed the best goodness of fit by achieving the lowest values of Akaike (AIC) and Bayesian (BIC) information criteria and the best predictive performance based on the highest value of c-index. The overall median survival was significantly longer for patients with than without textbook outcome (69.0 vs 20.1 months, P < 0.001). TO maintained its prognostic value in a multivariate model controlling for age, sex, comorbidities, treatment, and tumour related variables and was associated with a 39% lower risk of death (HR 0.61, 95%CI 0.51 – 0.73, P < 0.001). Nine variables identified as predictors of TO were used to develop a nomogram showing very good correlation between the predicted and actual probability of achieving TO. The AUC of ROC obtained from the nomogram was 0.752 (95% CI 0.727 to 0.781).ConclusionsA uniform definition of textbook outcome provides clinically relevant prognostic information and could be used in quality improvement programs for gastric cancer patients.

Perineural invasion confers poorer clinical outcomes in patients with T1/T2 intrahepatic cholangiocarcinoma: a single center, retrospective cohort study.

Intrahepatic cholangiocarcinoma (ICC) poses a significant clinical challenge, demanding a thorough understanding of prognostic indicators for effective patient management. Despite reports suggesting the impact of perineural invasion (PNI) on the prognosis of early-stage ICC patients, there has been a dearth of comprehensive research specifically targeting this subgroup. This study seeks to investigate the influence of PNI on survival outcomes in early-stage ICC patients and aims to enhance the prognostic value of the American Joint Committee on Cancer (AJCC) T category. A cohort of 268 early-stage (T1-T2N0M0) ICC patients, who underwent curative-intent resection (R0) between 2011 and 2015 at the Eastern Hepatobiliary Surgery Hospital, were enrolled in this study. Lasso and Cox regression analyses were employed to explore differences in clinical and prognostic data. Kaplan-Meier curves were generated to illustrate the clinical significance of the combination of PNI and T category. Among the 268 patients, 24.6% exhibited PNI. Patients with PNI demonstrated shorter recurrence-free survival (RFS) [median RFS: 16 months (interquartile range, 9.5-19 months)] and overall survival (OS) [median OS: 16.53 months (interquartile range, 10-25 months)]. PNI emerged as an independent risk factor for both RFS and OS in T1- and T2-stage patients (all P<0.05), whereas tumor size was only an independent risk factor for OS (P=0.004). PNI was associated with all prognostic markers for ICC patients, including gender, jaundice, cholangitis, hepatitis B virus (HBV) infection, cancer antigen 199 (CA199), preoperative serum albumin, and preoperative platelet count (all P<0.05). However, there was no significant difference in RFS (P=0.270) and OS (P=0.360) between T2 patients without PNI and T1 patients with PNI. This study underscores PNI as a robust prognostic factor in early-stage ICC, emphasizing the necessity of incorporating PNI into the AJCC T category for precise risk stratification. Clinically, understanding the impact of PNI on survival outcomes can guide tailored treatment strategies for early ICC patients.

Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection.

Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection. Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set. Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification. An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.

Postoperative morbidity after simultaneous versus staged resection of synchronous colorectal liver metastases: Impact of hepatic tumor burden

BackgroundWe sought to characterize the risk of postoperative complications relative to the surgical approach and overall synchronous colorectal liver metastases tumor burden score. MethodsPatients with synchronous colorectal liver metastases who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Propensity score matching was employed to control for heterogeneity between the 2 groups. A virtual twins analysis was performed to identify potential subgroups of patients who might benefit more from staged versus simultaneous resection. ResultsAmong 976 patients who underwent liver resection for synchronous colorectal liver metastases, 589 patients (60.3%) had a staged approach, whereas 387 (39.7%) patients underwent simultaneous resection of the primary tumor and synchronous colorectal liver metastases. After propensity score matching, 295 patients who underwent each surgical approach were analyzed. Overall, the incidence of postoperative complications was 34.1% (n = 201). Among patients with high tumor burden scores, the surgical approach was associated with a higher incidence of postoperative complications; in contrast, among patients with low or medium tumor burden scores, the likelihood of complications did not differ based on the surgical approach. Virtual twins analysis demonstrated that preoperative tumor burden score was important to identify which subgroup of patients benefited most from staged versus simultaneous resection. Simultaneous resection was associated with better outcomes among patients with a tumor burden score <9 and a node-negative right-sided primary tumor; in contrast, staged resection was associated with better outcomes among patients with node-positive left-sided primary tumors and higher tumor burden score. ConclusionAmong patients with high tumor burden scores, simultaneous resection of the primary tumor and liver metastases was associated with an increased incidence of postoperative complications.

Prognostic significance of a five-factor modified frailty index in patients with gastric cancer undergoing curative-intent resection: A cohort study.

The 5-factor modified frailty index (mFI-5) evaluates frailty based on variables including functional status, diabetes, chronic obstructive pulmonary disease, congestive heart failure, and hypertension requiring medication. Despite its effectiveness in predicting surgical risk, the potential of mFI-5 as a predictor of long-term survival in patients with gastric cancer (GC) has not been investigated. This study aims to assess the prognostic significance of mFI-5 in patients with GC who have undergone curative-intent gastric resection. Among the 494 patients diagnosed with stage I to III GC, multivariate analysis revealed that age, tumor-node-metastasis (TNM) stage, geriatric nutritional risk index, mFI-5, and the type of gastrectomy were significant predictors for both overall survival (OS) and disease-free survival (DFS). We assessed 3 models: Baseline model (BM, TNM stage only), interim model (IM, all significant variables except mFI-5), and full model (FM, all significant variables including mFI-5). FM outperformed BM for OS (C-index 0.818 vs 0.683; P < .001) and DFS (C-index 0.805 vs 0.687; P < .001). Similarly, IM outperformed BM for OS (C-index 0.811 vs 0.683; P < .001) and DFS (C-index 0.797 vs 0.687; P < .001). Multiple metrics consistently supported the improved discriminative capacity of FM and IM compared to BM. However, while FM exhibits enhanced predictive capacity over IM, this improvement lacks statistical significance across key metrics. In conclusion, our study highlights the clinical significance of the mFI-5, along with age, TNM stage, geriatric nutritional risk index, and type of gastrectomy, as valuable predictors of long-term survival in GC patients. The FM consistently demonstrates enhanced predictive accuracy compared to the BM. However, it is important to note that while the FM improves predictive power over the IM, this enhancement does not achieve statistical significance across multiple metrics. These findings collectively emphasize the potential clinical value of the FM as a robust tool for surgeons in predicting long-term survival outcomes before surgery in patients with GC.

Role of routine lymph node dissection alongside resection of intrahepatic cholangiocarcinoma: Systematic review and meta-analysis

BACKGROUND The global incidence of intrahepatic cholangiocarcinoma (ICCA) is soaring. Due to often delayed presentation, only a narrow spectrum of the disease is usually surgically resectable. To more accurately stage the disease, reduce recurrence, and improve overall survival, surgical teams are increasingly performing intraoperative lymph node dissection (LND) as well. This procedure has its associated morbidity, while there is no consensus or formal guidelines on its role in this setting. Hence, there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA. AIM To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA. METHODS We performed a systematic literature search using Pubmed, Medline, Embase, and the Cochrane Library, for all studies involving LND, ICCA, and surgical resection using several keywords, Medical Subject Headings (MeSH) tags, and appropriate synonyms. All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included, while single-arm case series, studies with insufficient data, and duplicates were excluded. We included all English-language studies from the different academic databases up till early December 2022. The primary outcome measures were set for overall survival (OS) and disease-free survival (DFS). RESULTS This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA, of whom 6424 (56.3%) underwent hepatectomy with LND while the remainder underwent hepatectomy only. In patients who underwent LND, on average, 27.7% of the resected lymph nodes were positive for metastatic disease. Overall, the results showed that performing LND did not significantly improve OS or DFS. However, the effect of LND on OS showed a degree of variability by geographical region, in Eastern and Western countries. As LND is increasingly being performed, further time-based analysis was undertaken to identify time-dependent changes in the role of LND. An increasing adoption of LND was not associated with improved OS. Furthermore, no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either. CONCLUSION LND might aid in staging, prognosticating, and deciding further management of resected ICCA, but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.

Adjuvant Immunotherapy in Curative Intent Esophageal Cancer Resection Patients: Real-World Experience within an Integrated Health System.

Adjuvant immunotherapy has been shown in clinical trials to prolong the survival of patients with esophageal cancer. We report our initial experience with immunotherapy within an integrated health system. A retrospective cohort study was performed reviewing patients undergoing minimally invasive esophagectomy at our institution between 2017 and 2021. The immunotherapy cohort was assessed for completion of treatment, adverse effects, and disease progression, with emphasis on patients who received surgery in 2021 and their eligibility to receive nivolumab. There were 39 patients who received immunotherapy and 137 patients who did not. In logistic regression, immunotherapy was not found to have a statistically significant impact on 1-year overall survival after adjusting for age and receipt of adjuvant chemoradiation. Only seven patients out of 39 who received immunotherapy successfully completed treatment (18%), with the majority failing therapy due to disease progression or side effects. Of the 17 patients eligible for nivolumab, 13 patients received it (76.4%), and three patients completed a full course of treatment. Despite promising findings of adjuvant immunotherapy improving the survival of patients with esophageal cancer, real-life practice varies greatly from clinical trials. We found that the majority of patients were unable to complete immunotherapy regimens with no improvement in overall 1-year survival.

Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype.

Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well aspropose modifications of the current classification system. Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed. Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001). ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy.

Immunotherapy Plus Locoregional Therapy Leading to Curative-Intent Hepatectomy in HCC: Proof of Concept Producing Durable Survival Benefits Detectable with Liquid Biopsy.

Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing pCR to immunotherapy + LRT as a proof of concept for the proposed treatment approach for locally unresectable HCC. Patients with unresectable HCC treated with immunotherapy as an intended destination therapy from 2016 to 2023 were included. The electronic health record was queried for oncologic information, locoregional therapies, surgical interventions, and long-term outcomes. Circulating tumor DNA (ctDNA) testing was obtained using Guardant360, and tumor mutational burden (TMB) was defined as the number of somatic mutations per megabase. Ninety-six patients with advanced HCC received immunotherapy + LRT as a destination therapy. In total, 11 of 96 patients showed a complete response according to mRECIST criteria. Four of these (36.4%) ultimately underwent curative-intent resection. The median follow-up was 24.9 (IQR 15.6-38.3) months. Overall survival rates in those with complete response at 1, 3, and 5 years were 100%, 91%, and 81.8%, respectively, which were significantly improved compared to those of the cohort not achieving pCR (p < 0.001). All four patients undergoing immunotherapy + LRT followed by curative-intent hepatectomy have no evidence of disease (NED). Of those undergoing surgery, ctDNA was cleared in 75% (n = 3), providing an additional objective measurement of complete response. All four patients were TMB+ before beginning this treatment course, with three being TMB-, indicating stable and complete disease response. Immunotherapy + locoregional therapy can help downstage a significant proportion of patients with initially unresectable HCC, allowing for curative-intent surgery. The survival benefit associated with complete response seems durable up to 3 years after achieving this response. ctDNA measurement was converted from positive to negative in this cohort, providing additional indication of response.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial

BackgroundThe efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. MethodsIn this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). Results35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%−96%) among evaluable patients (n = 32), and 95% (95% CI 70–100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15–23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1–19). Treatment toxicity was manageable, without toxic death. ConclusionHAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

Digestive cancer surgery in low-mid income countries: analysis of postoperative mortality and complications in a single-center study.

This study aimed to analyze postoperative and 90-day morbidity and mortality and their risk factors in all digestive cancer curative intent resections of a single digestive surgical department in a low-mid income country. All consecutive patients who underwent a surgical resection for digestive cancer with a curative intent between January 1, 2021, and December 31, 2021, were included. This is a retrospective analysis of a prospective cancer surgery database managed during the period. Patterns and factors associated with increased morbidity and mortality were analyzed and presented in tabular and descriptive forms. Seventy-six patients were included, 38 (50%) were men with a mean age of 59 years (±13.5). Forty patients (52.63%) had tumors locally advanced, staged CT3-CT4 on preoperative imagery. Thirty-three of our population (43.42%) had laparoscopic surgery (conversion rate at 12.12%). In immediate preoperative, the morbidity rate was 36.84%; among each, 7 patients (9.21%) had serious complications (>2 Clavien-Dindo grade), and mortality rate was 5.26%. At 90 days after surgery, morbidity remained the same, and mortality increased to 7.9%. Risk factors for increased morbidity and mortality were female gender, obesity, high levels of carcinoembryonic antigen, hypoalbuminemia, laparotomy approach, hand sewn anastomosis, prolonged operating time, and wide drainage (p < 0.05). This study provides figures on mortality and morbidity related to digestive cancer curative surgery in a low-mid income country digestive department and discusses risk factors increasing postoperative complications and death.

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial

No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully. F Hoffmann-La Roche/Genentech.

Primary versus Salvage Liver Transplantation after Curative-Intent Resection or Radiofrequency Ablation for Hepatocellular Carcinoma: Long-Term Oncological Outcomes.

Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma After Curative Resection.

To define the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). DAC and iAC share a similar histologic differentiation but the benefit of adjuvant therapy remains unclear. Patients undergoing curative intent surgical resection for DAC and iAC between 2010 and 2021 at 5 high-volume centers were included. Patient baseline, perioperative, and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in patients with DAC was 101 months versus 155 months for patients with iAC ( P = 0.098). DAC had a higher rate of local (14.1% vs 1.2%, P < 0.001) and systemic recurrence (30.4% vs 3.5%, P < 0.001). Adjuvant therapy failed to improve OS in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors, had improved OS rates with adjuvant therapy (72 vs 44m, P = 0.044). Patients with iAC with N+ (190 vs 57m, P = 0.003), T3-T4 (177 vs 59m, P = 0.050), and perineural invasion (150 vs 59m, P = 0.019) had improved OS rates with adjuvant therapy. While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved OS in patients with DAC with perineural invasion and in patients with iAC with T3-T4 tumors, positive lymph nodes, and perineural invasion.

Surveillance With Serial Imaging and CA 19-9 Tumor Marker Testing After Resection of Pancreatic Cancer: A Single-Center Retrospective Study.

Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center. We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence. We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis ( P =0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk ( P <0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72-0.95) and specificity of 87% (0.76-0.98) for identification of recurrence within 2 years of pancreatectomy. CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.

Using the win ratio to compare laparoscopic versus open liver resection for colorectal cancer liver metastases.

We sought to assess the overall benefit of laparoscopic versus open hepatectomy for treatment of colorectal liver metastases (CRLMs) using the win ratio, a novel methodological approach. CRLM patients undergoing curative-intent resection in 2001-2018 were identified from an international multi-institutional database. Patients were paired and matched based on age, number and size of lesions, lymph node status and receipt of preoperative chemotherapy. The win ratio was calculated based on margin status, severity of postoperative complications, 90-day mortality, time to recurrence, and time to death. Among 962 patients, the majority underwent open hepatectomy (n=832, 86.5%), while a minority underwent laparoscopic hepatectomy (n=130, 13.5%). Among matched patient-to-patient pairs, the odds of the patient undergoing laparoscopic resection "winning" were 1.77 [WR: 1.77, 95% confidence interval (CI): 1.42-2.34]. The win ratio favored laparoscopic hepatectomy independent of low (WR: 2.94, 95% CI: 1.20-6.39), medium (WR: 1.56, 95% CI: 1.16-2.10) or high (WR: 7.25, 95% CI: 1.13-32.0) tumor burden, as well as unilobar (WR: 1.71, 95% CI: 1.25-2.31) or bilobar (WR: 4.57, 95% CI: 2.36-8.64) disease. The odds of "winning" were particularly pronounced relative to short-term outcomes (i.e., 90-day mortality and severity of postoperative complications) (WR: 4.06, 95% CI: 2.33-7.78). Patients undergoing laparoscopic hepatectomy had 77% increased odds of "winning". Laparoscopic liver resection should be strongly considered as a preferred approach to resection in CRLM patients.

Optimal policy tree to assist in adjuvant therapy decision-making after resection of colorectal liver metastases

BackgroundAlthough systemic postoperative therapy after surgery for colorectal liver metastases is generally recommended, the benefit of adjuvant chemotherapy has been debated. We used machine learning to develop a decision tree and define which patients may benefit from adjuvant chemotherapy after hepatectomy for colorectal liver metastases. MethodsPatients who underwent curative-intent resection for colorectal liver metastases between 2000 and 2020 were identified from an international multi-institutional database. An optimal policy tree analysis was used to determine the optimal assignment of the adjuvant chemotherapy to subgroups of patients for overall survival and recurrence-free survival. ResultsAmong 1,358 patients who underwent curative-intent resection of colorectal liver metastases, 1,032 (76.0%) received adjuvant chemotherapy. After a median follow-up of 28.7 months (interquartile range 13.7–52.0), 5-year overall survival was 67.5%, and 3-year recurrence-free survival was 52.6%, respectively. Adjuvant chemotherapy was associated with better recurrence-free survival (3-year recurrence-free survival: adjuvant chemotherapy, 54.4% vs no adjuvant chemotherapy, 46.8%; P < .001) but no overall survival significant improvement (5-year overall survival: adjuvant chemotherapy, 68.1% vs no adjuvant chemotherapy, 65.7%; P = .15). Patients were randomly allocated into 2 cohorts (training data set, n = 679, testing data set, n = 679). The random forest model demonstrated good performance in predicting counterfactual probabilities of death and recurrence relative to receipt of adjuvant chemotherapy. According to the optimal policy tree, patient demographics, secondary tumor characteristics, and primary tumor characteristics defined the subpopulation that would benefit from adjuvant chemotherapy. ConclusionA novel artificial intelligence methodology based on patient, primary tumor, and treatment characteristics may help clinicians tailor adjuvant chemotherapy recommendations after colorectal liver metastases resection.

Low Prognostic Nutritional Index Is Common and Associated with Poor Outcomes following Curative-Intent Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors

Introduction: To investigate the impact of prognostic nutritional index (PNI) on short- and long-term outcomes of patients who underwent curative-intent resection for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Methods: Patients with GET-NETs who underwent curative-intent resection were identified from a multi-center database. The prognostic impact of clinicopathological factors including PNI on post-operative outcomes were evaluated. A novel nomogram was developed and externally validated. Results: A total of 2,099 patients with GEP-NETs were included in the training cohort; 255 patients were in the external validation cohort. Median PNI (n = 973) was 47.4 (IQR 43.1–52.4). At the time of presentation, 1,299 (61.9%) patients presented with some type of clinical symptom. Low-PNI (≤42.2) was associated with gastrointestinal symptoms, as well as nodal metastasis and distant metastasis (all p < 0.05). Patients with a low PNI had a higher incidence of severe (≥Clavien-Dindo grade IIIa: low PNI 24.9% vs. high PNI 15.4%, p = 0.001) and multiple (≥3 types of complications: low PNI 14.5% vs. high PNI 9.2%, p = 0.024) complications, as well as a worse overall survival (OS)(5-year OS, low PNI 73.7% vs. high PNI 88.5%, p < 0.001), and RFS (5-year RFS, low PNI 68.5% vs. high PNI 79.8%, p = 0.008) versus patients with high PNI (>42.2). A nomogram based on PNI, tumor grade and metastatic disease demonstrated excellent discrimination and calibration to predict OS in both the training (C-index 0.748) and two external validation (C-index 0.827, 0.745) cohorts. Conclusions: Low PNI was common and associated with worse short- and long-term outcomes among patients with GEP-NETs.