Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

BACKGROUND: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. METHODS: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. RESULTS: The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. CONCLUSIONS: Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Adjuvant Chemotherapy With or Without Radiotherapy for Resected Pancreatic Cancer After Multiagent Neoadjuvant Chemotherapy.

BACKGROUND: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting. METHODS: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup. RESULTS: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors. CONCLUSION: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.

Conversion surgery for initially unresectable locally advanced biliary tract cancer: A multicenter collaborative study conducted in Japan and Korea.

BACKGROUND: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.

Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study.

OBJECTIVE: The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. METHODS: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. RESULTS: In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. CONCLUSIONS: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.

Pulmonary metastasectomy is associated with survival after lung-only recurrence in pancreatic cancer.

BACKGROUND: After surgical resection of pancreatic ductal adenocarcinoma, 14% of patients have lung-only recurrence. We hypothesize that in patients with isolated lung metastases from pancreatic ductal adenocarcinoma, pulmonary metastasectomy offers a survival benefit with minimal additional morbidity after resection. METHODS: This was a single-institution, retrospective study of patients who underwent definitive resection of pancreatic ductal adenocarcinoma and later developed isolated lung metastases between 2009 and 2021. Patients were included if they carried a diagnosis of pancreatic ductal adenocarcinoma, underwent pancreatic resection with curative intent, and subsequently developed lung metastases. Patients were excluded if they developed multiple sites of recurrence. RESULTS: We identified 39 patients with pancreatic ductal adenocarcinoma and isolated lung metastases, 14 of whom underwent pulmonary metastasectomy. During the study period, 31 (79%) patients died. Across all patients, there was an overall survival of 45.9 months, a disease-free interval of 22.8 months, and survival after recurrence of 22.5 months. Survival after recurrence was significantly longer in patients who underwent pulmonary metastasectomy than those who did not (30.8 months vs 18.6 months, P < .01). There was no difference in overall survival between groups. However, patients who underwent pulmonary metastasectomy were significantly more likely to be alive 3 years after their diagnosis (100.0% vs 64%, P = .02) and 2 years after recurrence (79% vs 32%, P < .01) than those in who did not undergo pulmonary metastasectomy. No mortalities occurred related to pulmonary metastasectomy, and procedure-related morbidity was 7%. CONCLUSION: Patients who underwent pulmonary metastasectomy for isolated pulmonary pancreatic ductal adenocarcinoma metastases had significantly longer survival after recurrence and clinically meaningful survival benefit with minimal additional morbidity after pulmonary resection.

"Conversion surgery" for locally advanced pancreatic cancer: A position paper by the study group at the joint meeting of the International Association of Pancreatology (IAP) & Japan Pancreas Society (JPS) 2022.

Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.

Management of Localized Small- and Large-Cell Pancreatic Neuroendocrine Carcinoma in the National Cancer Database.

BACKGROUND: The role of curative-intent resection and perioperative chemotherapy for nonmetastatic pancreatic neuroendocrine carcinoma (PanNEC) remains unclear due to their biological aggressiveness and rarity. This study aimed to evaluate the association of resection and perioperative chemotherapy with overall survival for nonmetastatic PanNEC. STUDY DESIGN: Patients with localized (cT1-3, M0), small- and large-cell PanNEC were identified in the National Cancer Database from 2004 to 2017. The changing trends in terms of the annual proportions of resection and adjuvant chemotherapy were assessed. The survival of patients who received resection and those who received adjuvant chemotherapy were investigated using Kaplan-Meier estimates and Cox regression models. RESULTS: In total, 199 patients with localized small- and large-cell PanNEC were identified; 50.3% of those were resected, and 45.0% of the resected patients received adjuvant chemotherapy. Rate of resection and adjuvant treatment has trended upward since 2011. The resected group was younger, was more often treated at academic institutions, had more distal tumors, and had a lower number of small-cell PanNEC. The median overall survival was longer in the resected group compared to the unresected group (29.4 months vs 8.6 months, p < 0.001). Resection was associated with improved survival in a multivariable Cox regression model adjusting for preoperative factors (adjusted hazard ratio 0.58, 95% CI 0.37 to 0.92), while adjuvant therapy was not. CONCLUSIONS: This nationwide retrospective study suggests that resection is associated with improved survival in patients with localized PanNEC. The role of adjuvant chemotherapy needs more investigation.

Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors.

Importance: The number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear. Objective: To evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival. Design, Setting, and Participants: This cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022. Exposures: Patients with vs without surgical resection. Main Outcomes and Measures: The primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model. Results: Of the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P < .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection. Conclusions and Relevance: Findings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

Prevalence and progression of intraductal papillary mucinous neoplasms of the pancreas in solid organ transplant recipients: A systematic review.

Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in this population remains unclear. We performed a systematic review by searching PubMed, Embase, Scopus, and Google Scholar. All studies containing IPMNs in solid organ transplantation recipients were screened. We included 11 studies in our final analysis, totaling 274 patients with IPMNs of the 8213 SOT recipients. The prevalence from 8 studies was 4.7% (95% CI 2.4%-7.7%) in a random-effects model with median study periods of 24 to 220 months. The median rate for all progressions from 10 studies was 20% (range, 0%-88%) within 13 to 41 months of the median follow-up time. By utilizing the results of 3 case-control studies, the relative risk from a random-effects model for progression (worrisome features and high-risk stigmata) of IPMNs was 0.39 (95% CI 0.12-1.31). No adenocarcinoma derived from IPMN was reported in the included studies. Overall, this study indicates that the progression of pretransplant IPMN does not increase drastically compared with the general nontransplant population. However, considering the limited literature, further studies are required for confirmation.

Association of Adjuvant Chemotherapy in Patients With Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy.

Importance: The total number of patients with pancreatic ductal adenocarcinoma (PDAC) who receive neoadjuvant chemotherapy (NAC) is increasing. However, the added role of adjuvant chemotherapy (AC) in these patients remains unknown. Objective: To evaluate the association of AC with overall survival (OS) in patients with PDAC who received multiagent NAC followed by curative-intent surgery. Design, Setting, and Participants: This retrospective, matched-cohort study used data from the National Cancer Database and included patients with PDAC diagnosed between 2010 and 2018. The study included patients at least 18 years of age who received multiagent NAC followed by surgical resection and had available records of the pathological findings. Patients were excluded if they had clinical or pathological stage IV disease or died within 90 days of their operation. Exposures: All included patients received NAC and underwent resection for primary PDAC. Some patients received adjuvant chemotherapy. Main Outcomes and Measures: The main outcome was the OS of patients who received AC (AC group) vs those who did not (non-AC group). Interactions between pathological findings and AC were investigated in separate multivariable Cox regression models. Results: In total, 1132 patients (mean [SD] age, 63.5 [9.4] years; 577 [50.1%] male; 970 [85.7%] White) were included, 640 patients in the non-AC group and 492 patients in the AC group. After being matched by propensity score according to demographic and pathological characteristics, 444 patients remained in each group. The multivariable Cox regression model adjusted for all covariates revealed an association between AC and improved survival (hazard ratio, 0.71; 95% CI, 0.59-0.85; P < .001). Subgroup interaction analysis revealed that AC was significantly associated with better OS (26.6 vs 21.2 months; P = .002), but the benefit varied by age, pathological T category, and tumor differentiation. Of note, AC was associated with better survival in patients with any pathological N category and positive margin status. Conclusions and Relevance: In this cohort study, AC following multiagent NAC and resection in patients with PDAC was associated with significant survival benefit compared with that in patients who did not receive AC. These findings suggest that patients with aggressive tumors may benefit from AC to achieve prolonged survival, even after multiagent NAC and curative-intent resection.

Advances in the management of pancreatic cancer.

Pancreatic cancer remains among the malignancies with the worst outcomes. Survival has been improving, but at a slower rate than other cancers. Multimodal treatment, including chemotherapy, surgical resection, and radiotherapy, has been under investigation for many years. Because of the anatomical characteristics of the pancreas, more emphasis on treatment selection has been placed on local extension into major vessels. Recently, the development of more effective treatment regimens has opened up new treatment strategies, but urgent research questions have also become apparent. This review outlines the current management of pancreatic cancer, and the recent advances in its treatment. The review discusses future treatment pathways aimed at integrating novel findings of translational and clinical research.

Immune subtypes and neoantigen-related immune evasion in advanced colorectal cancer.

Elimination of cancerous cells by the immune system is an important mechanism of protection from cancer, however, its effectiveness can be reduced owing to development of resistance and evasion. To understand the systemic immune response in advanced untreated primary colorectal cancer, we analyze immune subtypes and immune evasion via neoantigen-related mechanisms. We identify a distinctive cancer subtype characterized by immune evasion and very poor overall survival. This subtype has less clonal highly expressed neoantigens and high chromosomal instability, resulting in adaptive immune resistance mediated by the immune checkpoint molecules and neoantigen presentation disorders. We also observe that neoantigen depletion caused by immunoediting and high clonal neoantigen load are correlated with a good overall survival. Our results indicate that the status of the tumor microenvironment and neoantigen composition are promising new prognostic biomarkers with potential relevance for treatment plan decisions in advanced CRC.

Prediction of early recurrence of pancreatic ductal adenocarcinoma after resection.

BACKGROUND: Even after curative resection, pancreatic ductal adenocarcinoma (PDAC) patients suffer a high rate of recurrence. There is an unmet need to predict which patients will experience early recurrence after resection in order to adjust treatment strategies. METHODS: Data of patients with resectable PDAC undergoing surgical resection between January 2005 and September 2018 were reviewed to stratify for early recurrence defined as occurring within 6 months of resection. Preoperative data including demographics, tumor markers, blood immune-inflammatory factors and clinicopathological data were examined. We employed Elastic Net, a sparse modeling method, to construct models predicting early recurrence using these multiple preoperative factors. As a result, seven preoperative factors were selected: age, duke pancreatic monoclonal antigen type 2 value, neutrophil:lymphocyte ratio, systemic immune-inflammation index, tumor size, lymph node metastasis and is peripancreatic invasion. Repeated 10-fold cross-validations were performed, and area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate the usefulness of the models. RESULTS: A total of 136 patients was included in the final analysis, of which 35 (34%) experienced early recurrence. Using Elastic Net, we found that 7 of 14 preoperative factors were useful for the predictive model. The mean AUC of all models constructed in the repeated validation was superior to the standard marker CA 19-9 (0.718 vs 0.657), whereas the AUC of the model constructed from the entire patient cohort was 0.767. Decision curve analysis showed that the models had a higher mean net benefit across the majority of the range of reasonable threshold probabilities. CONCLUSION: A model using multiple preoperative factors can improve prediction of early resectable PDAC recurrence.

Quantification of multicellular colonization in tumor metastasis using exome-sequencing data.

Metastasis is a major cause of cancer-related mortality, and it is essential to understand how metastasis occurs in order to overcome it. One relevant question is the origin of a metastatic tumor cell population. Although the hypothesis of a single-cell origin for metastasis from a primary tumor has long been prevalent, several recent studies using mouse models have supported a multicellular origin of metastasis. Human bulk whole-exome sequencing (WES) studies also have demonstrated a multiple "clonal" origin of metastasis, with different mutational compositions. Specifically, there has not yet been strong research to determine how many founder cells colonize a metastatic tumor. To address this question, under the metastatic model of "single bottleneck followed by rapid growth," we developed a method to quantify the "founder cell population size" in a metastasis using paired WES data from primary and metachronous metastatic tumors. Simulation studies demonstrated the proposed method gives unbiased results with sufficient accuracy in the range of realistic settings. Applying the proposed method to real WES data from four colorectal cancer patients, all samples supported a multicellular origin of metastasis and the founder size was quantified, ranging from 3 to 17 cells. Such a wide-range of founder sizes estimated by the proposed method suggests that there are large variations in genetic similarity between primary and metastatic tumors in the same subjects, which may explain the observed (dis)similarity of drug responses between tumors.

Laparoscopic left lateral sectionectomy: A three-port method.

BACKGROUND: Laparoscopic liver resection has become popular recent years. Laparoscopic left lateral sectionectomy (LLS) is now a standard operation with sufficient safety and feasibility. To improve the benefits of minimally invasive surgery, we invented and have been performing a reduced port LLS procedure using 3 ports since 2009. MATERIALS AND METHODS: All patients who underwent LLS at Toranomon Hospital (Tokyo, Japan) were included, except for patients with a previous history of upper abdominal surgery or those who had undergone the simultaneous resection of another organ. An essential point of this procedure was the extracorporeal traction of the divided round ligament using a ligature. As a result, the operator was able to perform the parenchymal transection within a good operative field. RESULTS: Twelve patients were enrolled in the study. All the patients had a Child-Pugh classification of Class A. The median indocyanine green retention rate at 15 min was 9.5%. Compared with previously reported results for conventional LLS, the median operation time (82.5 min), blood loss (0 mL) and rate of blood transfusion (0%) were lower for the 3-port LLS procedure. The rates of complications (9%) and a positive surgical margin (0%) were similar to those reported for the conventional approach. CONCLUSION: Three-port LLS appears to be a safe and feasible procedure.

Expanded Makuuchi's criteria using estimated indocyanine green clearance rate of future liver remnant as a safety limit for maximum extent of liver resection.

BACKGROUND: Recent advances in liver surgery have dramatically improved the safety of hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes for patients fulfilling an extended criteria vs. those fulfilling the conventional criteria based on the bilirubin and indocyanine green (ICG) clearance (Makuuchi's criteria). METHODS: The short term outcomes of patients undergoing hepatectomy for HCC and who fulfilled the expanded criteria (ICG clearance of future remnant liver [ICG-Krem] ≥ 0.05 estimated using 3-D volumetry) were retrospectively reviewed and were compared between those fulfilling the conventional criteria. Postoperative hepatic insufficiency (PHI) was defined as peak total bilirubin >7 mg/dL. RESULTS: A total of 323 patients undergoing resection of whom 269 (83%) met conventional criteria (In-M) and 54 (17%) extended criteria (Ex-M). The overall morbidity rates were not significantly different. The incidence of PHI was 0.37% in In-M and 3.7% in Ex-M (P = 0.074), with no liver-related deaths. When the ICG-Krem ≥ 0.05 criterion was included, major hepatectomy was performed in 24 patients (41%) in Ex-M with no significant increase in major morbidity (13%), PHI(3.3%), or liver-related death (0%) compared with minor hepatectomy (n = 30) in Ex-M(10%, 4% and 0%, respectively). CONCLUSIONS: Objective criteria using ICG clearance rate and 3-D volumetry may offer opportunities for safe surgical resection in selected patients exceeding the conventional criteria.

Platelet-Albumin Score as a Sensitive Measure for Surgical Risk Prediction and Survival Outcomes of Patients with Hepatocellular Carcinoma.

BACKGROUND: Given that patients with hepatocellular carcinoma (HCC) usually suffer from dual diseases (i.e., HCC and underlying liver disease), a complete survival estimation model is difficult to establish because both the oncological stage and the underlying liver function affect the survival outcome. METHODS: A new surgical risk model for estimating the survival of patients undergoing resection for HCC was created using a cohort treated between 1995 and 2013 (training set, n = 889), and its efficacy was then validated using a cohort treated between 2014 and 2017 (validation set, n = 310). RESULTS: The following statistical model was developed based on the results of multivariate analysis: albumin-platelet (PAL) score = - 0.777 × albumin (g/dL) - 0.575 × log10 (platelet count [104/µL]) (cut-off value, - 3.77 and - 3.04 for grading). A time-dependent receiver-operating curve analysis revealed that the area under the curve for 3-year survival was 0.644 in the training set and 0.666 in the validation set. The incidences of postoperative morbidity were 14.0% for PAL grade 1, 18.7% for PAL grade 2, and 26.1% for PAL grade 3 (P = 0.039), while the incidences of refractory ascites were 2.2, 7.1, and 12.5% (P = 0.005), respectively, in the training set. The reproducibility of these results was confirmed in the validation set with morbidity rates of 13.5, 23.3, and 40.7% (P = 0.003), respectively, and the incidences of refractory ascites were 0.7, 10.7, and 22.2% (P < 0.0001), respectively. CONCLUSIONS: The PAL score can be used as a grading system for the stratification of survival outcomes and surgical risks of patients undergoing HCC resection.

Postoperative low hepatitis C virus load predicts long-term outcomes after hepatectomy for hepatocellular carcinoma.

BACKGROUND: Preoperative hepatitis C virus (HCV) viral load is known to predict long-term outcomes after hepatectomy for HCV-related hepatocellular carcinoma (HCC). This study sought to examine the hypothesis that postoperative and preoperative HCV viral-load have similar prognostic implications, as well as determine a target viral-load that will improve long-term postoperative outcomes. METHOD: One hundred and eighty-one patients who underwent curative hepatectomy for HCV-related HCC were divided into five groups according to time-weighted average viral load. The cumulative-recurrence curves of the five groups were compared to identify prognostic trends. The optimal cut-off viral load value related to recurrence was also investigated. RESULTS: The five cumulative-recurrence curves were separated into two clusters according to viral load. Patients with a negative viral load had comparable recurrence curves to patients with the lowest viral-load (P = 0.907); both of these patient groups had more favorable outcomes than patients with a viral load categorized in the other groups (all P < 0.050). The optimal cut-off based on maximum HR method (> or ≤4.0 log10 IU/mL) was a strong prognostic indicator of recurrence in multivariate analysis (HR 3.09; 95%CI 1.96-5.04; P < 0.001). CONCLUSION: Postoperative HCV viral load correlated with long-term surgical outcomes. A low viral load (≤4.0 log10 IU/mL) independently predicted better long-term outcomes.

Fluorine-18-fluorodeoxyglucose positron emission tomography as an objective substitute for CT morphologic response criteria in patients undergoing chemotherapy for colorectal liver metastases.

PURPOSE: The computed tomography (CT) morphologic response of colorectal liver metastases (CLM) after chemotherapy is reportedly correlated with pathologic response and survival outcomes of patients undergoing surgery. However, they are rather subjective criteria and not evaluable without adequate quality of contrast-enhanced CT images. This study sought the potential use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) as an objective substitute for predicting pathological viability of CLM after chemotherapy. METHODS: Predictive ability of tumor viability of ≤10% was compared between FDG-PET/CT and contrast-enhanced CT in 34 patients who underwent curative surgical resection for CLM after chemotherapy. The CT morphology and response were defined according to the reported criteria (Chun YS, JAMA 2009). RESULTS: The mean standard uptake value (SUV-mean) in CLM was significantly lower in patients with group 1 and group 2 CT morphology (median, 2.53 and 3.00, respectively) than in group 3 (median, 3.32). The tumor SUV-mean showed moderate correlation with the tumor pathologic viability (r = 0.660, P < 0.0001). A receiver operating characteristic curve analysis revealed that both the tumor SUV-mean (area under the curve [AUC], 0.916; the cut-off value, 3.00) and the CT morphology (AUC, 0.882) have excellent predictive power for ≤10% of tumor viability, while degree of tumor shrinkage showed lower predictive power (AUC, 0.692). CONCLUSIONS: FDG-PET shows significant correlation with pathologic viability of CLM after chemotherapy and may offer additional objective information for estimating tumor viability when the CT morphologic response is not evaluable.