Oligo-like liver metastasis: A novel prognostic indicator to improve survival in pancreatic cancer.

Purpose: Whether surgical intervention for patients with oligometastatic recurrence can improve their post-recurrent prognosis is unclear. In this study, we introduce a novel concept of oligometastasis in post-surgical pancreatic ductal adenocarcinoma (PDAC) patients with hepatic recurrence, which we call "oligo-like liver metastasis (OLLM)." Patients with OLLM have better post-recurrence prognosis and could therefore be eligible for surgical intervention. Methods: A total of 121 PDAC patients who underwent radical resection, and who had an initial and single-organ metastasis to the liver, were analyzed. Independent prognostic factors for overall survival after recurrence (OSAR) were examined, and patients with all of these factors were defined as OLLM. The clinicopathological features and post-recurrent prognosis of OLLM patients were evaluated. In addition, a detailed analysis using the oligo-score, which was based on the prognostic factors, was performed. Results: The prognostic analysis revealed that short recurrence-free interval (RFI) (<6 months), short stable disease interval (SDI) (≤3 months), and four or more recurrent tumors were independent poor prognostic factors. OLLM patients were defined as those with all three conditions: long RFI (≥6 months), long SDI (>3 months), and three or less recurrent tumors. OLLM patients had a significantly better prognosis for OSAR than non-OLLM patients (HR = 0.272, p < 0.001). Further analysis demonstrated that the OSAR of patients could be stratified using the oligo-score, which was calculated based on the prognostic factors. Conclusion: We recommend that OLLM should be used to predict which patients are most likely to experience better post-recurrent prognosis after surgery with curative intent.

Impact of Surgical Margin Status on Survival and Recurrence After Pancreaticoduodenectomy for Distal Cholangiocarcinoma: Is Microscopic Residual Tumor (R1) Associated with Higher Rates of Local Recurrence?

BACKGROUND: Patients undergoing macroscopically curative resection for distal cholangiocarcinoma (DCC) have high recurrence rates and poor prognoses. This study aimed to investigate the impact of surgical margin status on survival and recurrence after resection of DCC, specifically focusing on microscopic residual tumor (R1) and its relationship to local recurrence. PATIENTS AND METHODS: This was a retrospective analysis of patients who had undergone pancreaticoduodenectomy (PD) for DCC between 2005 and 2021. Surgical margin was classified as R0, R1cis (positive bile duct margin with carcinoma in situ), and R1inv (positive bile duct margin with an invasive subepithelial component and/or positive radial margin). RESULTS: In total, 29 of 133 patients (21.8%) had R1cis and 23 (17.3%) R1inv. The 5-year overall survival (OS) for R0 (55.7%) did not differ significantly from that for R1cis/R1inv (47.4%/33.6%, respectively). The 5-year recurrence-free survival (RFS) for R0 was significantly longer than that for R1inv (50.1% vs. 17.4%, p = 0.003), whereas RFS did not differ significantly between those with R0 and R1cis. R1cis/R1inv status was not an independent predictor of OS and RFS in multivariate analysis. Cumulative incidence of isolated distant recurrence was significantly higher for R1cis/R1inv than for R0 (p = 0.0343/p = 0.0226, respectively), whereas surgical margin status was not significantly associated with rates of local or local plus distant recurrence. CONCLUSIONS: Surgical margin status does not significantly impact OS and RFS in patients undergoing PD for DCC following precise preoperative imaging evaluation. Additionally, R1 status is significantly linked to higher isolated distant recurrence rather than local recurrence, highlighting the importance of multidisciplinary therapy.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Cost-effectiveness of surveillance intervals after curative resection of colorectal cancer.

BACKGROUND: Major guidelines consistently recommend 5 years of postoperative surveillance for patients with colorectal cancer. However, they differ in their recommendations for examination intervals and whether they should vary according to disease stage. Furthermore, there are no reports on the cost-effectiveness of the different surveillance schedules. The objective of this study is to identify the most cost-effective surveillance intervals after curative resection of colorectal cancer. METHODS: A total of 3701 patients who underwent curative surgery for colorectal cancer at the National Cancer Center Hospital were included. A cost-effectiveness analysis was conducted for the five surveillance strategies with reference to the guidelines. Expected medical costs and quality-adjusted life years after colorectal cancer resection were calculated using a state-transition model by Monte Carlo simulation. The incremental cost-effectiveness ratio per quality-adjusted life years gained was calculated for each strategy, with a maximum acceptable value of 43 500-52 200 USD (5-6 million JPY). RESULTS: Stages I, II and III included 1316, 1082 and 1303 patients, respectively, with 45, 140 and 338 relapsed cases. For patients with stage I disease, strategy 4 (incremental cost-effectiveness ratio $26 555/quality-adjusted life year) was considered to be the most cost-effective, while strategies 3 ($83 071/quality-adjusted life year) and 2 ($289 642/quality-adjusted life year) exceeded the threshold value. In stages II and III, the incremental cost-effectiveness ratio for strategy 3 was the most cost-effective option, with an incremental cost-effectiveness ratio of $18 358-22 230/quality-adjusted life year. CONCLUSIONS: In stage I, the cost-effectiveness of intensive surveillance is very poor and strategy 4 is the most cost-effective. Strategy 3 is the most cost-effective in stages II and III.

Pathological complete response of initially unresectable multiple liver metastases achieved using combined peptide receptor radionuclide therapy and somatostatin analogs following pancreatic neuroendocrine tumor resection: a case report.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) serves as a novel and effective treatment option for somatostatin receptor-positive unresectable liver metastases of pancreatic neuroendocrine tumors (PNETs). However, there are few reported cases of surgical resection for initially unresectable liver metastases of PNET that were converted to resectable after PRRT. Here we report a case where PRRT and somatostatin analogs (SSAs) led to a pathological complete response of initially unresectable multiple liver metastases following PNET resection. CASE PRESENTATION: A 52-year-old man underwent pylorus-preserving pancreaticoduodenectomy for PNET at age 40 and subsequent hepatectomies for resectable liver metastases at 44 and 47 years of age. At age 48, a follow-up examination revealed unresectable multiple liver metastases, and PRRT with 177Lu-DOTATATE therapy was initiated. After four cycles of PRRT, most liver metastases diminished according to imaging studies, and the remaining two hepatic lesions continued to shrink with additional lanreotide. Conversion surgery for liver metastases was successfully performed, revealing no viable tumor cells in tissue specimens. Seventeen months after surgery, imaging showed no detectable residual tumor or recurrence. We present a review of the relevant literature that highlights the significance of our findings. CONCLUSIONS: This rare case highlights the pathological complete response of initially unresectable multiple liver metastases achieved by PRRT and SSAs following PNET resection, suggesting their potential as a multimodality treatment option for unresectable PNET.

Clinicopathological Findings and Treatment Outcomes of Patients with Primary Hepatobiliary Neuroendocrine Neoplasms: A Retrospective Single-institution Analysis.

Objective Primary hepatobiliary neuroendocrine neoplasms (NENs) are rare tumors exhibiting several morphological and behavioral characteristics. Considering the lack of relevant data on this topic, we evaluated the clinicopathological features and treatment outcomes of patients with primary hepatobiliary NENs. Methods/Patients We examined 43 consecutive patients treated at the National Cancer Center Hospital with pathological diagnoses of primary hepatobiliary NEN between 1980 and 2016. Results Nine patients were diagnosed with neuroendocrine tumor (NET) G1, 9 with NET G2, and 25 with neuroendocrine carcinoma (NEC) based on the World Health Organization 2019 classification. Patients with NEC had primary sites across the hepatobiliary organs, although sites in patients with NET G1 and NET G2 only included the liver and ampulla of Vater. Patients with primary extrahepatic bile duct or ampulla of Vater NENs tended to be diagnosed earlier than patients with primary gallbladder NENs. The median survival times in the NET G1, NET G2, and NEC groups were 167.9, 97.4, and 11.1 months, respectively. A good performance status, absence of distant metastases, and low tumor grade were identified as independent predictors of a favorable prognosis. Conclusion The NET-to-NEC ratio and tumor stage distribution at the diagnosis differed depending on the primary site. Patients with G1 and G2 NETs who underwent surgical resection had good prognoses, whereas those with NEC exhibited more advanced disease and poorer prognoses. The performance status, staging classification, and tumor grade are important factors to consider when devising an appropriate treatment strategy and predicting the prognoses of patients with primary hepatobiliary NEN.

Correlation of Vein-Rich Tumor Microenvironment of Intrahepatic Cholangiocarcinoma With Tertiary Lymphoid Structures and Patient Outcome.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer composed of large-duct and small-duct types. Understanding the tumor immune microenvironment and its related vascular system is important for developing novel and efficient therapies. We focused on tertiary lymphoid structure (TLS) as a hallmark of antitumor immunity and investigated the clinicopathologic significance of TLSs and the influence of vascular microenvironment on TLS formation in iCCAs. We examined 261 iCCA cases clinicopathologically and analyzed the vascular system using immunohistochemistry. Single-cell (102,685 cells) and bulk RNA (33 iCCA cases) sequencing analyses were performed using data sets downloaded from public databases, and endothelial cell characteristics in iCCA tissues and functional networks related to the tumor microenvironment were bioinformatically examined. High densities of both intratumoral and peritumoral TLSs were significantly associated with prolonged survival only in large-duct-type iCCA. Multivariate analyses showed that peritumoral TLS was a prognostic factor for the large-duct type. TLS-rich iCCA had a significantly higher vein density and tumor-infiltrating T-cell count than TLS-poor iCCA. Both the presence of TLSs and high vein endothelial cells in iCCA tissues were significantly associated with molecular networks representing active immune responses in transcriptomic analysis. Vein density was a prognostic factor in patients with large-duct and small-duct types. This suggests that TLS formation is involved in a microenvironment with high vein density, which represents an antitumor-directed immune microenvironment.

Novel insights into the intraepithelial spread of extrahepatic cholangiocarcinoma: clinicopathological study of 382 cases on extrahepatic cholangiocarcinoma.

Background: Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive disease and consisted of conventional eCCA and intraductal papillary neoplasm of the bile duct (IPNB). Intraepithelial spread (IES) of cancer cells beyond the invasive area is often observed in IPNBs; however, the prevalence of IES remains to be examined in conventional eCCAs. Here, we evaluated the clinicopathological features of eCCAs according to tumor location, with a focus on the presence of IES. The IES extension was also compared among biliary tract cancers (BTCs). Methods: We examined the prevalence and clinicopathological significance of IES in eCCAs (n=382) and the IES extension of BTCs, including gallbladder (n=172), cystic duct (n=20), and ampullary cancers (n=102). Results: Among the invasive eCCAs, IPNB had a higher rate of IES (89.2%) than conventional eCCAs (57.0%). Among conventional eCCAs, distal eCCAs (75.4%) had a significantly higher prevalence of IES than perihilar eCCAs (41.3%). The presence of IES was associated with a significantly higher survival rate in patients with distal eCCAs (P=0.030). Extension of the IES into the cystic duct (CyD) in distal eCCAs that cancer cells reached the junction of the CyD was a favorable prognostic factor (P<0.001). The association of survival with IES, either on the extrahepatic bile duct or on the CyD, differed depending on the tumor location and type of eCCA. The extension properties of IES were also dependent on different types of tumors among BTCs; usually, the IES incidence became higher than 50% in the tissues that the tumor developed, whereas IES extension to other tissues decreased the incidence. Conclusion: Thus, eCCAs have different clinicopathological characteristics depending on the tumor location and type.

Objective Definition and Optimized Strategy for "Biologically Borderline Resectable" Colorectal Liver Metastases.

BACKGROUND: The prognostic benefit of preoperative chemotherapy leading to conversion surgery for unresectable colorectal liver metastases (CRLM) is well recognized, while that of neoadjuvant chemotherapy (NAC) compared with upfront surgery (UFS) for resectable CRLM is negligible. This study aims to assess the prognostic benefit and search for optimal indication of NAC for resectable advanced CRLM by establishing an objective definition of biologically borderline resectable (bBR) CRLM. METHODS: A bicentric retrospective analysis of patients with CRLM undergoing curative-intent initial liver resection between 2007 and 2021 was performed. An original classification matrix was established, which reassessed technical resectability using virtual hepatectomy and oncological favorability using Beppu's nomogram. Patients with technically resectable but biologically unfavorable CRLM were classified into the bBR group. The propensity score matching analysis using preoperatively available factors was performed to assess long-term outcomes of the bBR-UFS and bBR-NAC groups. RESULTS: Of 831 patients reviewed, 240 were categorized into the bBR group: bBR -UFS (n = 139) and bBR-NAC (n = 101). Ten (10%) in the bBR-NAC group (n = 101) experienced biological status change from unfavorable to favorable after NAC (Biological Conversion) and showed significantly longer overall survival (hazard ratio 5.63, 95% confidence interval 1.37-23.1; P = 0.016) than the bBR-UFS group. However, after propensity score matching, no significant difference between the UFS and NAC groups (n = 67 for each) was found in long-term outcomes. CONCLUSIONS: NAC for bBR-CRLM did not enhance the prognostic impact of the following liver resection, except for a limited number of optimal candidates experiencing the Biological Conversion.

Short- and long-term outcomes of laparoscopic radical gallbladder resection for gallbladder carcinoma: A multi-institutional retrospective study in Japan.

BACKGROUND/PURPOSE: Laparoscopic resection of gallbladder carcinomas remains controversial. This study aimed to evaluate the surgical and oncological outcomes of laparoscopic procedures for suspected gallbladder carcinoma (GBC). METHODS: In this retrospective study, data regarding suspected GBC treated with laparoscopic radical cholecystectomy before 2020 in Japan, was included. Patient characteristics, surgical procedure details, surgical outcomes, and long-term outcomes were analyzed. RESULTS: Data of 129 patients with suspected GBC who underwent laparoscopic radical cholecystectomy were retrospectively collected from 11 institutions in Japan. Among them, 82 patients with pathological GBC were included in the study. Laparoscopic gallbladder bed resection was performed in 114 patients and laparoscopic resection of segments IVb and V was performed in 15 patients. The median operation time was 269 min (range: 83-725 min), and the median intraoperative blood loss was 30 mL (range: 0-950 mL). The conversion and postoperative complication rates were 8% and 2%, respectively. During the follow-up period, the 5-year overall survival rate was 79% and the 5-year disease-free survival rate was 87%. Recurrence was detected in the liver, lymph nodes, and other local tissues. CONCLUSION: Laparoscopic radical cholecystectomy is a treatment option with potential favorable outcomes in selected patients with suspected GBC.

Efficacy of endoscopic ultrasound-guided tissue acquisition for solid pancreatic lesions 20 mm or less in diameter suspected as neuroendocrine tumors or requiring differentiation.

BACKGROUND: For non-functioning pancreatic neuroendocrine tumors (pNETs) ≤ 20 mm, most guidelines consider follow-up observations as an option; however, the various treatment strategies are defined by size alone, even though the Ki-67 index is important for malignancy grading. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is the standard for the histopathological diagnosis of solid pancreatic lesions; however, recent results for small lesions remain unclear. Therefore, we examined the efficacy of EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation and the non-increase rate in tumor size in follow-up cases. METHODS: We retrospectively analyzed data of 111 patients (median age = 58 years) with lesions ≤ 20 mm suspected as pNETs or requiring differentiation who underwent EUS-TA. All patients underwent specimen evaluation by rapid onsite evaluation (ROSE). RESULTS: EUS-TA led to a diagnosis of pNETs in 77 patients (69.4%) and tumors other than pNETs in 22 patients (19.8%). The histopathological diagnostic accuracy of EUS-TA was 89.2% (99/111) overall, 94.3% (50/53) for 10-20 mm lesions, and 84.5% (49/58) for ≤ 10 mm lesions, with no significant difference in diagnostic accuracy (p = 0.13). The Ki-67 index was measurable in all patients with a histopathological diagnosis of pNETs. Among 49 patients with a diagnosis of pNETs who were followed up, one patient (2.0%) showed tumor enlargement. CONCLUSIONS: EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation is safe and has adequate histopathological diagnostic accuracy, suggesting that follow-up observations of pNETs with a histological pathologic diagnosis are acceptable in the short term.

Cost-effectiveness analysis of computer-aided detection systems for colonoscopy in Japan.

OBJECTIVES: The usefulness of computer-aided detection systems (CADe) for colonoscopy has been increasingly reported. In many countries, however, data on the cost-effectiveness of their use are lacking; consequently, CADe for colonoscopy has not been covered by health insurance. We aimed to evaluate the cost-effectiveness of colonoscopy using CADe in Japan. METHODS: We conducted a simulation model analysis using Japanese data to examine the cost-effectiveness of colonoscopy with and without CADe for a population aged 40-74 years who received colorectal cancer (CRC) screening with a fecal immunochemical test (FIT). The rates of receiving FIT screening and colonoscopy following a positive FIT were set as 40% and 70%, respectively. The sensitivities of FIT for advanced adenomas and CRC Dukes' A-D were 26.5% and 52.8-78.3%, respectively. CADe colonoscopy was judged to be cost-effective when its incremental cost-effectiveness ratio (ICER) was below JPY 5,000,000 per quality-adjusted life-years (QALYs) gained. RESULTS: Compared to conventional colonoscopy, CADe colonoscopy showed a higher QALY (20.4098 vs. 20.4088) and lower CRC incidence (2373 vs. 2415 per 100,000) and mortality (561 vs. 569 per 100,000). When the CADe cost was set at JPY 1000-6000, the ICER per QALY gained for CADe colonoscopy was lower than JPY 5,000,000 (JPY 796,328-4,971,274). The CADe cost threshold at which the ICER for CADe colonoscopy exceeded JPY 5,000,000 was JPY 6040. CONCLUSIONS: Computer-aided detection systems for colonoscopy has the potential to be cost-effective when the CADe cost is up to JPY 6000. These results suggest that the insurance reimbursement of CADe for colonoscopy is reasonable.

Enhanced Recognition Confidence of Millimeter-Sized Intrahepatic Targets by Real-Time Virtual Sonography.

OBJECTIVES: Real-time virtual sonography (RVS) is an artificial-intelligence-assisted ultrasonographic navigation system that displays synchronized preoperative computed tomography (CT) images corresponding to real-time intraoperative ultrasonograms (IOUS). This study aimed to investigate whether RVS can enhance IOUS identification of small intrahepatic targets found in preoperative CT. METHODS: Patients with small intrahepatic targets detected by preoperative thin-slice dynamic CT before liver resection were included. The targets included millimeter-sized liver tumors or a third-order or more distal portal branch and were marked on CT images using 3D simulation software. After laparotomy, the targets were searched using fundamental IOUS, and participating liver surgeons subjectively scored the target identifying confidence on a scale of 1-5 (5 points for detection with the highest confidence and one point for undetectable). Then, the search procedure was repeated using the RVS, and the scores were compared. RESULTS: Totally, 55 patients with 117 small targets were investigated. The median target size was 6.0 mm, and the median registration time was 3.6 seconds. The target identification confidence score significantly increased from 2.78 to 4.52 points after using RVS. Seventeen targets (14.5%) were undetectable in fundamental IOUS, and 14 of them were identified by RVS. The detectability of small liver tumors (2-5 points of identification confidence) by IOUS was 81.1 and 96.7% by RVS. CONCLUSION: RVS enhanced surgeons' confidence in identifying millimeter-sized intrahepatic targets found in preoperative CT.

Novel Insights Into Immunohistochemical Analysis For Acinar Cell Neoplasm of The Pancreas: Carboxypeptidase A2, Carboxypeptidase A1, and Glycoprotein 2.

Acinar cell carcinoma (ACC) is a rare and highly malignant pancreatic tumor. Owing to histologic similarity, ACC is often difficult to distinguish from other solid medullary pancreatic tumors, particularly neuroendocrine neoplasm (NEN) and intraductal tubulopapillary neoplasm (ITPN). We aimed to identify new immunohistochemical markers commonly expressed in tumor cells with acinar cell differentiation and useful for both surgical and small biopsy specimens. Candidate molecules exclusively expressed in neoplastic or non-neoplastic acinar cells in pancreatic tissues with specific and available antibodies suitable for immunohistochemistry were selected. We selected carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and glycoprotein 2 (GP2), which were expressed in 100%, 100%, and 96% of cases, respectively, in ACC (n=27) or neoplasia with acinar cell differentiation, including mixed acinar-neuroendocrine carcinoma (n=9), mixed acinar-ductal carcinoma (n=3), pancreatoblastoma (n=4), and acinar cystic transformation (n=2), in the cytoplasm of tumor cells with a granular pattern. Both CPA2 and CPA1 were not expressed in any other tumors without acinar cell differentiation, including NEN (n=44), pancreatic ductal adenocarcinoma (n=44), and ITPN (n=4). GP2 was not expressed in these tumors except in rare cases, including 14% of NEN, 15% of intraductal papillary-mucinous neoplasm, 25% of intraductal oncocytic papillary neoplasm, 25% of ITPN, and 7% of pancreatic ductal adenocarcinoma, wherein a small proportion of tumor cells expressed GP2 in their apical cell membrane. NEN cases also showed cytoplasmic GP2 expression. Therefore, CPA2, CPA1, and potentially GP2 may act as ACC markers.

Prognostic Role for Primary Tumor Location in Patients With Colorectal Liver Metastases: A Comparison of Right-Sided Colon, Left-Sided Colon, and Rectum.

BACKGROUND: Although right-sided colon cancer is increasingly recognized as having a worse prognosis than left-sided colorectal cancer for colorectal liver metastases, little is known about the differences between the left-sided colon and rectum. OBJECTIVE: This study evaluated the prognostic value of primary tumor location in patients with colorectal liver metastases by examining the left-sided colon and rectum separately. DESIGN: This was a retrospective study from 2003 to 2017. SETTINGS: The study was conducted in a National Cancer Center Hospital. PATIENTS: The study cohort included 489 patients with colorectal liver metastases from right-sided colon cancer ( n = 119, 24%), left-sided colon cancer ( n = 251, 51%), or rectal cancer ( n = 119, 24%) who underwent hepatic resection. MAIN OUTCOME MEASURES: Primary outcomes were relapse-free survival and overall survival. RESULTS: Five-year relapse-free survival rates for patients with right-sided colon cancer, left-sided colon cancer, and rectal cancer were 28.6%, 34.1%, and 26.4%, and 5-year overall survival rates were 53.9%, 70.3%, and 60.8%. Multivariable analysis revealed significant differences in relapse-free survival and overall survival between left-sided colon cancer and rectal cancer (relapse-free survival: HR = 1.37, p = 0.03; overall survival: HR = 1.49, p = 0.03) and between left-sided colon cancer and right-sided colon cancer (relapse-free survival: HR = 1.39, p = 0.02; overall survival: HR = 1.60, p = 0.01), but not between right-sided colon cancer and rectal cancer. In patients with recurrence ( n = 325), left-sided colon cancer had the lowest multiple-site recurrence rate and the highest surgical resection rate for recurrence (left-sided colon cancer, 20%/46%; right-sided colon cancer, 32%/30%; rectal cancer, 26%/39%). LIMITATIONS: This study was retrospective in design. CONCLUSIONS: Rectal cancer was associated with worse relapse-free survival and overall survival compared with left-sided colon cancer in patients with colorectal liver metastases who underwent hepatic resection. Our findings suggest that the left-sided colon and rectum should be considered distinct entities in colorectal liver metastases. See Video Abstract at http://links.lww.com/DCR/B882 . PAPEL PRONSTICO DE LA UBICACIN DEL TUMOR PRIMARIO EN PACIENTES CON METSTASIS HEPTICAS COLORRECTALES UNA COMPARACIN ENTRE COLON DERECHO, COLON IZQUIERDO Y RECTO: ANTECEDENTES:Aunque se reconoce cada vez más que el cáncer de colon del lado derecho tiene un peor pronóstico que el cáncer colorrectal del lado izquierdo para las metástasis hepáticas colorrectales, se sabe poco acerca de las diferencias entre el recto y el colon del lado izquierdo.OBJETIVO:Este estudio evaluó el valor pronóstico de la ubicación del tumor primario en pacientes con metástasis hepáticas colorrectales examinando el recto y el colon del lado izquierdo por separado.DISEÑO:Este fue un estudio retrospectivo de 2003 a 2017.ENTORNO CLÍNICO:El estudio se llevó a cabo en un Hospital del Centro Nacional de Cáncer.PACIENTES:La cohorte del estudio incluyó a 489 pacientes con metástasis hepáticas colorrectales de cáncer de colon del lado derecho (n = 119, 24%), cáncer de colon del lado izquierdo (n = 251, 51%) o cáncer de recto (n = 119, 24%). %) que fueron sometidos a resección hepática.PRINCIPALES MEDIDAS DE VALORACIÓN:Los resultados primarios fueron la supervivencia sin recaídas y la supervivencia general.RESULTADOS:Las tasas de supervivencia sin recaída a cinco años para los pacientes con cáncer de colon derecho, cáncer de colon izquierdo y cáncer de recto fueron del 28,6%, 34,1%, y 26,4%, respectivamente, y las tasas de supervivencia general a los 5 años fueron del 53,9%, 70,3%, y 60,8%, respectivamente. El análisis multivariable reveló diferencias significativas en la supervivencia sin recaída y la supervivencia general entre el cáncer de colon izquierdo y el cáncer de recto (supervivencia sin recaída: HR = 1,37, p = 0,03; supervivencia general: HR = 1,49, p = 0,03) y entre el cáncer de colon izquierdo y el cáncer de colon del lado derecho (supervivencia libre de recaídas: HR = 1,39, p = 0,02; supervivencia global: HR = 1,60, p = 0,01), pero no entre el cáncer de colon del lado derecho y el cáncer de recto. En pacientes con recurrencia (n = 325), el cáncer de colon izquierdo tuvo la tasa de recurrencia en sitios múltiples más baja y la tasa de resección quirúrgica más alta por recurrencia (cáncer de colon izquierdo, 20%/46%; cáncer de colon derecho, 32%/30%; cáncer de recto, 26%/39%).LIMITACIONES:Este estudio fue de diseño retrospectivo.CONCLUSIONES:El cáncer de recto se asoció con una peor supervivencia sin recaída y una supervivencia general peor en comparación con el cáncer de colon izquierdo en pacientes con metástasis hepáticas colorrectales que se sometieron a resección hepática. Nuestros hallazgos sugieren que el colon y el recto del lado izquierdo deben considerarse entidades distintas en las metástasis hepáticas colorrectales. Consulte Video Resumen en http://links.lww.com/DCR/B882 . (Tradducción-Dr. Ingrid Melo ).

Chronological improvement of pancreatectomy for resectable but advanced pancreatic neuroendocrine neoplasms.

BACKGROUND: Progress of non-surgical treatments in the last decade has improved the prognosis of pancreatic neuroendocrine neoplasms (PanNEN). However, the improvement of surgery for advanced PanNEN remains unknown. This study aimed to investigate the chronological changes of the clinical impact of pancreatectomy for PanNEN. METHODS: Patients undergoing curative-intent pancreatectomy for PanNEN between 1991 and 2010 were categorized into the earlier period group, and those between 2011 and 2021 were into the later period group. Advanced PanNEN was defined as showing resectable synchronous liver metastases or invasion to portal venous systems or adjacent organs. The recurrence-free survival (RFS) and overall survival (OS) were analyzed among patients with non-advanced and advanced PanNENs. The independent prognostic risk factors were identified using a Cox proportional hazard model. RESULTS: A total of 189 patients (n = 54 in the earlier period and n = 135 in the later period) were included. The proportion of advanced PanNEN increased from 15% to 30% (P = 0.027). The RFS and OS of non-advanced PanNEN were similar between the periods. Whereas, among patients with advanced PanNEN, the later period group showed improved prognosis; The 5-year RFS of the earlier period vs. the later period was 0% vs. 27%, and the 5-year OS was 38% vs. 82% (p = 0.013). CONCLUSIONS: A radical surgical treatment for advanced PanNEN has shown prognostic improvement in this decade. However, more careful perioperative examinations and possibly, additional treatments are required for PanNEN with portal vein invasion.

Prognostic impact of conversion hepatectomy for initially unresectable colorectal liver metastasis.

PURPOSE: This study aimed to evaluate the prognostic impact of conversion hepatectomy in patients with initially unresectable colorectal liver metastasis (CRLM) and to identify prognostic factors after conversion hepatectomy. METHODS: Correlations of conversion hepatectomy with relapse-free survival (RFS) and overall survival (OS) were retrospectively investigated in 554 consecutive patients who underwent hepatectomy for CRLM in 2000-2017. Prognostic factors after conversion hepatectomy were examined in multivariable analysis. RESULTS: Five hundred and nine patients (92%) had initially resectable CRLM at diagnosis and underwent hepatectomy (primary resection group) and 45 (8%) underwent conversion hepatectomy following chemotherapy (conversion group). The 5-year RFS was 30.0% in the primary resection group and 19.8% in the conversion group (p = 0.042); the respective 5-year OS rates were 62.0% and 52.4% (p = 0.253). Multivariable analysis did not identify conversion hepatectomy as a significant prognostic factor for RFS (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.64-1.37, p = 0.796) or OS (HR 1.12, 95% CI 0.67-1.79, p = 0.667). In the conversion group, multivariable analysis identified the following independent prognostic factors: timing of liver metastases for RFS (synchronous: HR 3.14, 95% CI 1.20-8.24, p = 0.020) and preoperative CEA level for RFS (> 5 ng/ml: HR 3.10, 95% CI 1.45-6.61, p = 0.003) and OS (> 5 ng/ml: HR 3.29, 95% CI 1.18-9.17, p = 0.023). CONCLUSIONS: RFS and OS rates after conversion hepatectomy were not inferior to those after primary resection in patients with CRLM. Patients with a normal CEA level before hepatectomy can be expected to have good long-term prognosis after conversion hepatectomy.

Clinical utility of comprehensive genomic profiling tests for advanced or metastatic solid tumor in clinical practice.

Previous clinical trials indicate that 10%-25% of patients received genomically matched therapy after comprehensive genomic profiling (CGP) tests. However, the clinical utility of CGP tests has not been assessed in clinical practice. We assessed the clinical utility of CGP tests for advanced or metastatic solid tumor and determined the proportion of patients receiving genomically matched therapy among those with common and non-common cancers. From August 2019 to July 2020, a total of 418 patients had undergone CGP tests, and the results were discussed through the molecular tumor board at our site. The median age of patients was 57 (range: 3-86) years. Colorectal cancer was the most common, with 47 (11%) patients. Actionable genomic alterations (median 3, range: 1-17) were identified in 368 (88.0%) of 418 patients. Druggable genomic alterations were determined in 196 (46.9%) of 418 patients through the molecular tumor board. Genomically matched therapy was administered as the subsequent line of therapy in 51 (12.2%) patients, which is comparable to the proportion we previously reported in a clinical trial (13.4%) (p = 0.6919). The proportion of patients receiving genomically matched therapy was significantly higher among those with common cancers (16.2%) than non-common cancers (9.4%) (p = 0.0365). Genomically matched therapy after the CGP tests was administered to 12.2% of patients, which is similar to the proportion reported in the previous clinical trials. The clinical utility of CGP tests in patients with common cancers greatly exceeded that in patients with non-common cancers.