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.

Multicenter validation study of a treatment selection MAP for pancreatic neuroendocrine tumors.

BACKGROUND: Somatostatin analogs, molecular-targeted agents and cytotoxic anticancer agents are available as therapeutic agents for the systemic treatment of pancreatic neuroendocrine tumors, and we have developed a first-line treatment selection MAP to enable selection of the optimal treatment strategy for pancreatic neuroendocrine tumors. The purpose of this study was to validate the usefulness of the treatment selection MAP. METHODS: Patients who had received systemic therapy for a pancreatic neuroendocrine tumor between January 2017 and December 2020 were compared according to whether they had been treated as recommended by the MAP (matched patients) or not (unmatched patients) to determine whether better outcomes were achieved by the matched patients. The primary endpoint was progression-free survival of the matched group and unmatched groups in the somatostatin analog, molecular-targeted agent and cytotoxic anticancer agents areas of the MAP. RESULTS: There were 41 (55%) MAP-matched patients in all areas among the 74 patients registered at seven hospitals. The MAP-matched rates were 100, 77 and 38% in the somatostatin analog area, molecular-targeted agent area and cytotoxic anticancer agents area, respectively. All of the unmatched patients had been selected for less intensive treatment. The median progression-free survival in the matched group and unmatched group in the molecular-targeted agent area of the MAP were 46.6 and 15.4 months, respectively, and a multivariate analysis identified MAP-matched (hazard ratio 0.18 [95% confidence interval: 0.04-0.87], P = 0.032) as the only significant independent favorable predictive factor. CONCLUSION: The usefulness of the MAP for treatment selection was validated in the molecular-targeted agent area of the MAP.

Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

Optimal first-line treatment strategies of systemic therapy for unresectable gastrointestinal neuroendocrine tumors based on the opinions of Japanese experts.

There are several options for systemic therapy of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), including somatostatin analogues (SSA), molecular-targeted agents, cytotoxic agents, and peptide receptor radionuclide therapy. However, the effectiveness of each agent varies according to the primary site. Although SSA and everolimus are key drugs used for systemic therapy of neuroendocrine tumors arising from the gastrointestinal tract (GI-NET), the optimal strategy for selecting among these modalities remains unexplored. Japanese experts on GI-NET discussed and determined optimal first-line treatment strategies based on the results of previously reported pivotal trials. The consensus was reached that tumor aggressiveness and prognosis can be predicted using hepatic tumor load and Ki-67 labeling index, which are thought to be clinically important factors when selecting systemic therapy for unresectable GI-NET. SSA therapy is considered appropriate for patients with a low hepatic tumor load and low Ki-67 value and everolimus for those with contraindications to SSA therapy. There was also agreement that the treatment strategy should be determined according to whether the origin is in the midgut, considering the biological differences. Based on this strategy, the experts have tentatively created treatment maps and applied them in representative cases of unresectable GI-NET. Japanese experts proposed tentative maps for optimal first-line treatment in patients with unresectable GI-NET. Further investigation is warranted to validate the usefulness of these maps.

Phase I/II study of streptozocin monotherapy in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: This phase I/II study was conducted to evaluate the efficacy, safety and pharmacokinetics of streptozocin (STZ) in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors. METHODS: Twenty-two patients received up to 4 cycles of intravenous STZ at either 500 mg/m2 once daily for 5 consecutive days every 6 weeks (daily regimen) or at 1000-1500 mg/m2 once weekly for 6 weeks (weekly regimen). Tumor response was evaluated using the modified RECIST criteria ver. 1.1, and adverse events were assessed by grade according to the National Cancer Institute CTCAE (ver. 4.0). RESULTS: Fourteen (63.6%) patients completed the study protocol. No patients had complete response; partial response in 2 (9.1%), stable disease in 17 (77.3%), non-complete response/non-progressive disease in 2 (9.1%) and only 1 (4.5%) had non-evaluable disease. Excluding the latter, the response rate in the daily and weekly regimens was 6.7% (1/15) and 16.7% (1/6), respectively, with an overall response rate of 9.5% (2/21). However, the best overall response in each patient showed that the disease control rate was 100%.Adverse events occurred in all 22 patients, including 17 grade 3 adverse events in 11 patients; however, no grade 4 or 5 adverse events were reported. Prophylactic hydration and antiemetic treatment reduced the severity and incidence of nephrotoxicity, nausea and vomiting. Plasma STZ concentrations decreased rapidly after termination of infusion, with a half-life of 32-40 min. Neither repeated administration nor dose increases affected pharmacokinetic parameters. CONCLUSIONS: STZ may be a useful option for Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

Laparoscopic surgery reduced frequency of postoperative small bowel obstruction, and hospital stay compared with open surgery in a cohort of patients with colorectal cancer: a propensity score matching analysis.

BACKGROUND: Laparoscopic surgery (LS) is reported to reduce postoperative complications and hospital stay compared with open surgery (OP). Because patient selection may have been biased in previous studies, propensity score matching (PSM) analysis was used in this study to test the benefits of LS compared with OP. METHODS: A total of 759 patients with stage I-III colorectal cancer undergoing curative surgery were retrospectively reviewed. To minimize confounding bias between LS and OP groups, a 1:1 PSM analysis was performed based on adjuvant chemotherapy, age, albumin, body mass index, American Society of Anesthesiologists physical status depth of tumor, gender, lymph node dissection, maximum tumor size, obstructive tumor, previous abdominal surgery, pathological stage, tumor differentiation, and tumor location. Statistical analyses including chi-square test, Mann-Whitney U test, univariate analyses and Kaplan-Meier method and log-rank test were performed using the data after PSM to investigate the benefits of LS compared with OP. RESULTS: After PSM analysis, 460 patients remained in the study. The LS group had lower intraoperative blood loss (34 ± 70 vs 237 ± 391, mL; P < 0.001), lower frequency of postoperative small bowel obstruction (SBO) (17/213 vs 30/230; P = 0.045), lower rate of nasogastric tube insertion (7/223 vs 17/213; P = 0.036), and shorter postoperative hospital stay (13 ± 10 vs 25 ± 47, day; P < 0.001) than the OP group. Univariate analyses showed that LS significantly reduced the risk of postoperative SBO (odds ratio [OR] 0.532; 95% confidence interval [CI] 0.285-0.995; P = 0.048) and nasogastric tube insertion (OR 0.393; 95% CI 0.160-0.967; P = 0.042) compared with OP. There were no significant differences in OS and RFS between the groups. CONCLUSIONS: LS reduced intraoperative blood loss, frequency of postoperative SBO, rate of nasogastric tube insertion, and postoperative hospital stay compared with OP.

The preoperative pan-immune-inflammation value is a novel prognostic predictor for with stage I-III colorectal cancer patients undergoing surgery.

PURPOSE: The pan-immune-inflammation value (PIV) is useful for stratifying outcomes in patients with metastatic colorectal cancer. However, it is unclear whether preoperative PIV can predict the surgical outcomes of patients with stage I-III colorectal cancer who receive surgery. METHODS: The records of 758 patients with stage I-III colorectal cancer who received surgical treatment were retrospectively reviewed. The preoperative PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The cut-off value was determined using a receiver operating characteristic curve for overall survival. RESULTS: The cut-off value of the preoperative PIV was 376. Five hundred sixty-eight patients (74.9%) had low values (≤ 376), and 190 (25.1%) had high values (> 376). Univariate and multivariate analyses revealed that the PIV (> 376/ ≤ 376) (HR 2.485; 95% CI 1.552-3.981, P < 0.001) was significantly associated with overall survival, as well as age (> 60/ ≤ 60, years) (HR 1.988; 95% CI 1.038-3.807, P = 0.038), globulin-to-albumin ratio (> 0.83/ ≤ 0.83) (HR 2.013; 95% CI 1.231-3.290, P = 0.005) and postoperative complication (C-D grade III-V/0-II) (HR 1.991; 95% CI 1.154-3.438, P = 0.013). The Kaplan-Meier method and log-rank test showed significant differences in overall survival between patients with stage I-III disease with high (> 376) and low (≤ 376) PIVs. CONCLUSION: The preoperative PIV is useful for predicting surgical outcomes in patients with stage I-III colorectal cancer.

Prognostic significance of preoperative hyaluronic acid level in patients with hepatocellular carcinoma.

BACKGROUND: Serum hyaluronic acid (HA) levels are increased in patients with solid tumors, and may predict outcomes. However, as HA levels also correlate with the degree of liver fibrosis, the prognostic significance of serum HA levels in patients with hepatocellular carcinoma (HCC) is unclear. METHODS: A total of 656 consecutive patients who underwent hepatic resection for HCC were divided into two groups by serum HA level (high HA [≥200 ng/mL], n = 248; low HA [<200 ng/mL], n = 408). Clinicopathological characteristics and postoperative survival were compared between groups. Moreover, 1:1 propensity score matching analysis was applied to adjust characteristics between groups. RESULTS: Both the 5-year overall and relapse-free survival rates (OSR and RFSR) in the low HA group were significantly better than those in the high HA group (59.8% vs. 38.6%, respectively, p < 0.001 and 24.5% vs. 13.1%, respectively, p < 0.001). After propensity score matching, two comparable groups of 124 patients each were obtained. However, both the 5-year OSR and RFSR in the low HA group remained significantly better than those in the high HA group (57.4% vs. 38.3%, respectively, p = 0.006 and 22.5% vs. 14.7%, respectively, p = 0.003). CONCLUSION: High preoperative HA level predicts poor postoperative survival of patients with HCC. undergoing hepatic resection.

Impact of Primary Tumor Location on Survival After Curative Resection in Patients with Colon Cancer: A Meta-Analysis of Propensity Score-Matching Studies.

BACKGROUND: Recent retrospective subgroup analyses of patients with unresectable colon cancer (CC) receiving systemic chemotherapy have demonstrated that there is a significant difference in treatment outcome between patients with right-sided CC (RSCC) and those with left-sided CC (LSCC). However, it is impossible to divide patients with CC randomly into RSCC and LSCC groups before surgery. Therefore, the aim of this study is to explore the impact of primary tumor location (PTL) on survival after curative surgery for patients with CC using propensity score-matching (PSM) studies instead of randomization. MATERIALS AND METHODS: We performed a comprehensive electronic search of the literature up to January 2019 to identify studies that had used databases allowing comparison of postoperative survival between patients with RSCC and those with LSCC. To integrate the impact of PTL on 5-year overall survival (OS) after curative surgery, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected PSM studies. RESULTS: Five studies involving a total of 398,687 patients with CC were included in this meta-analysis. Among 205,641 patients with RSCC, 69,091 (33.6%) died during the observation period, whereas among 193,046 patients with LSCC, 63,380 (32.8%) died during the same period. These results revealed that patients with RSCC and those with LSCC had almost the same 5-year OS (RR, 0.98; 95% CI, 0.89-1.07; p = .64; I2 = 97%). CONCLUSION: This meta-analysis has demonstrated that there was no significant difference in 5-year OS between patients with RSCC and those with LSCC after curative resection. IMPLICATIONS FOR PRACTICE: To integrate the impact of primary tumor location (PTL) on 5-year overall survival (OS) after curative surgery, five propensity score-matching (PSM) studies involving a total of 398,687 patients with colon cancer (CC) were included in this meta-analysis. Among 205,641 patients with right-sided CC (RSCC), 69,091 (33.6%) died during the observation period, whereas among 193,046 patients with left-sided CC (LSCC), 63,380 (32.8%) died during the same period. These results revealed that patients with RSCC and those with LSCC had almost the same 5-year OS (risk ratio, 0.98; 95% confidence interval, 0.89-1.07; p = .64; I2 = 97%).

PD-L1 is induced on the hepatocyte surface via CKLF-like MARVEL transmembrane domain-containing protein 6 up-regulation by the anti-HBV drug Entecavir.

Chronic hepatitis B is now controllable when treated with nucleoside reverse transcriptase inhibitors (NRTIs), which inhibit hepatitis B virus (HBV) replication. However, once the NRTIs are discontinued, most patients relapse, necessitating lifelong NRTIs treatment. HBV infection relapse is assumed to be caused by the persistent existence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. The mechanism by which cccDNA-positive hepatocytes escape immune surveillance during NRTIs treatment remains elusive. Entecavir (ETV), a commonly used NRTI, post-transcriptionally up-regulates programmed cell death-ligand 1 (PD-L1), an immune checkpoint molecule, on the cell surface of hepatocytes regardless of HBV infection. Up-regulation by ETV depends on up-regulation of CKLF-like MARVEL transmembrane domain-containing 6, a newly identified potent regulator of PD-L1 expression on the cell surface. ETV-treated hepatic cells suppressed the activity of primary CD3 T cells and programmed cell death protein-1 (PD-1)-over-expressed Jurkat cells. Finally, ETV induces PD-L1 in primary hepatocytes infected by HBV. These results provide evidence that ETV considerably up-regulates PD-L1 on the cell surface of infected hepatocytes, which may be one of the mechanisms by which infected hepatocytes subvert immune surveillance.

Omentectomy Does Not Affect the Postoperative Outcome of Patients With Locally Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To explore the influence of omentectomy on postoperative outcomes in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Although several meta-analyses have investigated the influence of bursectomy on postoperative outcomes in patients with LAGC, no meta-analyses have explored the influence of omentectomy on postoperative outcomes in such patients. METHODS: We performed a comprehensive electronic search of the literature up to December 2020 to identify studies that compared postoperative outcomes between patients with LAGC who did and did not undergo omentectomy. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I2 statistics. RESULTS: Eight retrospective studies involving a total of 2658 patients with LAGC who underwent surgery were included in this meta-analysis. Among them, 3 propensity score matching (PSM) studies demonstrated that the 5-y recurrence-free survival (RFS) rate was 72.9% (314/431) in patients with LAGC who did not undergo omentectomy, whereas it was 70.3% (303/431) in those who did. The results revealed no significant difference in 5-y RFS between groups (RR, 0.91; 95% CI, 0.74-1.13; P = 0.41; I2 = 0%). Two PSM studies also revealed no significant difference in 5-y overall survival (OS) between groups (RR, 0.77; 95% CI, 0.52-1.13; P = 0.18; I2 = 47%). CONCLUSIONS: The results of these meta-analyses show that omentectomy had no significant influence on 5-y OS, especially 5-y RFS, in patients with LAGC.

Analysis of Patient Outcome after Non-curative Resection for Hepatocellular Carcinoma Using Nationwide Survey Data in Japan.

BACKGROUND: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan. METHOD: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC). RESULTS: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively. CONCLUSION: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.

Optimal strategy of systemic treatment for unresectable pancreatic neuroendocrine tumors based upon opinion of Japanese experts.

BACKGROUND/OBJECTIVES: A number of therapeutic agents have been reported to be clinically useful for the management of the patients with unresectable pancreatic neuroendocrine tumors (PanNETs) including somatostatin analogues, molecular-targeted agents and cytotoxic agents. However, the optimal strategy for selection among those treatment modalities above in these patients has remained unexplored. METHODS: Japanese experts for PanNET discussed and determined the optimal treatment strategies according to the results of previously reported studies. RESULTS: The tumor volume of liver metastases and the Ki-67 labeling index were unanimously accepted as indicators of the tumor burden and tumor aggressiveness, respectively, which are two most clinically pivotal factors for determining the strategy of systemic treatment for unresectable PanNETs. In addition, for those with a relatively small tumor burden and slow disease progression, somatostatin analogues were selected as the first-line treatment agents. For those with a relatively large tumor burden and rapid tumor progression, cytotoxic agents were selected, possibly aiming at tumor shrinkage. For those of intermediate tumor volume and/or growth rate, molecular-targeted agents were selected as the first choice. Based on this strategy discussed among the experts, we tentatively prepared a MAP for proposing optimal treatment strategy and examined its validity in some patients with unresectable PanNETs. Results validated the usefulness of this MAP proposed for patients harbouring unresectable PanNETs. CONCLUSION: We herein propose a tentative MAP for optimal treatment selection for the patients harbouring unresectable PanNETs. Further large scale studies are, however, warranted to validate the usefulness of this MAP proposed in this study.

Is left-sided involvement of hepatocellular carcinoma an important preoperative predictive factor of poor outcome?

BACKGROUND: The tumor location is the most simple clinical factor and important in liver surgery to make surgical procedure. However, no previous study has investigated the prognostic differences and clinical features of hepatocellular carcinoma showing specific laterality. This study is the first report to focus on the laterality and aimed to lead to more simple and useful predictive factor rather than recent complicated predictive models. METHODS: Patients who underwent liver resection for the first time for single tumors located within each lobe between 2000 and 2018 were enrolled. We divided them into two groups based on tumor location: a right-sided group and a left-sided group. Univariable and multivariable analyses were performed to assess survival differences in relation to several other factors. RESULTS: There were 595 eligible patients; the 5-year survival rates and disease-free survival rates were 49.5% and 19.1% in the left-sided group and 55.6% and 24.5% in the right-sided group, respectively (p = 0.026). Statistical analyses revealed that the following preoperative prognostic factors were independently significant (p < 0.05) in the left-sided group: indocyanine green retention rate at 15 min, alpha fetoprotein, protein induced by vitamin K absence or antagonists-II level, and larger tumor size. CONCLUSION: The left-sided group had a poorer prognosis than the right-sided group. A left-sided tumor location is a significant preoperative factor predictive of poor outcome in patients with hepatocellular carcinoma.

[Preoperative C-reactive protein predicts recurrence after curative resection in advanced gastric cancer patients receiving postoperative adjuvant chemotherapy using S-1].

New chemotherapeutic regimens such as S-1 plus docetaxel, S-1 plus oxaliplatin and capecitabine plus oxaliplatin are reported to be effective and safe as postoperative adjuvant chemotherapy (PAC) for advanced gastric cancer (GC) patients. Although the use of these PACs is increasing, it is still unclear how to choose the best regimen for advanced GC patients. Therefore, we aimed to investigate which clinical characteristics are associated with recurrence after curative surgery in patients receiving S-1 as PAC. Thirty-nine patients who received a PAC regimen with S-1 for more than 1 year after curative surgery for advanced GC were enrolled. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with recurrence. Patients were divided into two groups, recurrence, and non-recurrence, and receiver operating characteristic (ROC) curve analysis was used to identify the cut-off values. Kaplan-Meier analysis and the log-rank test were used for comparison of relapse-free survival (RFS). Fifteen patients had a recurrence after surgery (38.5%, 15/39). Multivariate analysis using clinical characteristics revealed that preoperative C-reactive protein (CRP) (>0.3/≤0.3, mg/dL) (HR 10.73;95% C.I., 1.824-63.14;P=0.009) was significantly associated with recurrence. Kaplan-Meier analysis and the log-rank test demonstrated that preoperative CRP (>0.3/≤0.3, mg/dL) was also significantly associated with RFS (P<0.001). Therefore, preoperative CRP is significantly associated with recurrence and RFS after curative surgery in advanced GC patients receiving S-1 as PAC.

A high preoperative Glasgow prognostic score predicts a high likelihood of conversion from laparoscopic to open surgery in patients with colon cancer.

BACKGROUND: Although the use of laparoscopic resection for colon cancer (LRC) has been increasing, conversion to open surgery sometimes becomes necessary because of intraoperative difficulties. Although the Glasgow prognostic score (GPS) is well known to be a predictor of outcome in patients with various cancers, it is unclear whether the preoperative GPS can predict the need for conversion from laparoscopic to open surgery. OBJECTIVE: To investigate factors predictive of conversion from laparoscopic to open surgery in patients with colon cancer. METHODS: Data from 308 consecutive patients who underwent LRC between January 2006 and March 2017 were retrospectively enrolled. Preoperative clinical factors in patients who had undergone LRC were compared between conversion and non-conversion groups, and multivariate regression analysis was performed to identify preoperative factors that might predict conversion from laparoscopic to open surgery. RESULTS: Among 308 patients who had undergone LRC, conversion to open surgery was necessary in 28 (9.1%). Sixteen of the latter patients (6.8%) had GPS 0 (among a total of 234) and 6 (11.5%) had GPS 1 (among a total of 52). The proportion of patients with GPS 2 who required conversion was 27.2% (6/22), which was significantly higher than for those with GPS 0 or 1. Multivariate analysis demonstrated that GPS 2 (odds ratio [OR] 3.352; 95% confidence interval [CI] 1.049-10.71; p = 0.041) and preoperative ileus (OR 7.405; 95% CI 2.386-22.98; p = 0.001) were independent factors predictive of conversion from laparoscopic to open surgery. CONCLUSIONS: A high preoperative GPS is an independent factor predictive of conversion from laparoscopic to open surgery in patients with colon cancer.

Impact of Tumor Location on Postoperative Outcome of Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND: The concept of intraductal papillary neoplasm of the bile duct (IPNB) has been proposed to be the biliary equivalent of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. While the classification of IPMNs is based on their location of duct involvement, such classification has not been fully evaluated for IPNBs. The aim of this study is to investigate the value of IPNB classification based on its location. METHODS: A total of 306 consecutive patients who underwent surgical resection with a diagnosis of bile duct tumor were enrolled. Among these patients, 21 were diagnosed as having IPNB. The IPNBs were classified into two groups as follows: extrahepatic IPNB, which located in the distal or perihilar bile duct, and intrahepatic IPNB, which located more peripherally than the hilar bile duct. The clinicopathological features of the two groups were then compared. RESULTS: Extrahepatic IPNB tended to show more invasive characteristics than intrahepatic IPNB (presence of invasive component: 40.0 vs. 9.1%, p = 0.084). Moreover, patients with extrahepatic IPNB showed significantly poorer relapse-free survival (RFS) than those with intrahepatic IPNB [5-year RFS rate (%): 81.8 vs. 16.2, p = 0.014]. CONCLUSION: Patients with intrahepatic IPNB show more favorable pathological characteristics and postoperative survival outcomes than those with extrahepatic IPNB.

A Novel Approach for Hepatic Arterial Reconstruction after Total Pancreatectomy with Common Hepatic Artery Resection Using Inferior Phrenic Artery.

BACKGROUND/AIMS: Because of the anatomical characteristics, pancreatic cancers (PC) can easily invade to visceral vessels such as celiac artery, superior mesenteric artery, common hepatic artery (CHA) and portal vein, which makes curative resection difficult. In this study, we report an R0 resection for locally advanced PC by total pancreatectomy, combined resection of CHA, and reconstruction of hepatic artery using autologous left inferior phrenic artery (IPA). METHODS: A 47-year-old woman with complaints of low back pain was referred to our department. Contrast-enhanced computed tomography revealed a hypo-attenuation tumor of the pancreatic body measuring 70 mm, which completely encased the CHA. When unresectable locally advanced PC was diagnosed, systematic chemotherapy was administrated. After downstaging, she underwent surgery with curative intent. The tumor completely infiltrated the peripheral part of the CHA and gastroduodenal artery. As the tumor also extended to the head of the pancreas, total pancreatectomy and combined resection of CHA were performed. Then the exposed left IPA and proper hepatic artery were anastomosed with a microvascular technique. RESULTS: R0 resection was performed for restoring hepatic arterial flow and the postoperative course was uneventful without any postoperative morbidity. CONCLUSION: Hepatic artery reconstruction using IPA is a simple and safe procedure in selected patients.

An elevated neutrophil-to-lymphocyte ratio predicts a poor postoperative survival in primary hepatocellular carcinoma patients with a normal preoperative serum level of alpha-fetoprotein.

PURPOSE: Although alpha-fetoprotein (AFP) is a useful prognostic marker in patients with hepatocellular carcinoma (HCC), a recent study has shown that the preoperative neutrophil-to-lymphocyte ratio (NLR) is also associated with the postoperative survival in such patients. OBJECTIVE: To investigate the significance of the NLR in patients with primary HCC (p-HCC) showing a normal preoperative AFP. METHODS: Among 478 p-HCC patients undergoing curative surgery, 112 who had a normal AFP (< 8 ng/ml) were enrolled. The patients were divided into two groups: group A, who did not have an elevated NLR (≤ 3.2); and group B, who had an elevated NLR (> 3.2). Uni- and multivariate analyses were performed to compare clinical features with the overall survival (OS). RESULTS: A multivariate analysis of the clinical features showed that the NLR (> 3.2/≤ 3.2) (hazard ratio 2.366; 95% CI 1.069-5.235; P = 0.034) was closely associated with the OS, along with the age (> 65/≤ 65 years) (P = 0.033). Group B had a significantly lower survival ratio than group A in terms of not only the OS (P = 0.013), but also the cancer-specific survival (P = 0.002) and relapse-free survival (P = 0.039). CONCLUSIONS: An elevated NLR (> 3.2) is predictive of a poor survival in patients with primary HCC (p-HCC) showing normal AFP levels.