Relaparotomy pseudoaneurysm repair after distal pancreatectomy with celiac axis resection (DP-CAR): a case report.

A 76-year-old man underwent distal pancreatectomy with celiac axis resection (DP-CAR) after preoperative chemotherapy for pancreatic cancer with celiac artery invasion. Although postoperative pancreatic leakage and ischemia-induced bile fistula developed, the patient's condition remained stable with good drainage. On postoperative Day 47, a pseudoaneurysm developed at the junction of the gastroduodenal artery and proper hepatic artery. However, cannulation of the guidewire was difficult, and relaparotomy pseudoaneurysm repair was performed. On postoperative Day 56, a pseudoaneurysm reappeared at the same site, and relaparotomy was performed again. On postoperative Day 61, CT confirmed the disappearance of the pseudoaneurysm and preservation of the right and left hepatic arteries. The patient was discharged 107 days postoperatively. Interventional radiology (IVR) remains the best technique to achieve hemostasis for pseudoaneurysms. However, this case demonstrates that even when hemostasis by IVR is difficult, relaparotomy pseudoaneurysm repair after DP-CAR may be useful after some postoperative.

Pancreatic mixed acinar-neuroendocrine carcinoma with intraductal growth: A case report with radiologic-pathologic correlations.

Pancreatic mixed acinar-neuroendocrine carcinomas are rare malignant tumors of the pancreas. They are composed histologically of both acinar and neuroendocrine cells. The pancreatic duct is known to be an important site of tumor growth for acinar cell carcinomas, neuroendocrine tumors, and intraductal tubulopapillary neoplasms. To the best of our knowledge, there has been only 1 report of a mixed acinar-neuroendocrine carcinoma growing into the pancreatic duct and no reports detailing imaging findings with this tumor. We here report a 69-year-old man who presented with worsening glycemic control. Multiphase contrast-enhanced computed tomography and magnetic resonance imaging revealed a well-circumscribed mass with poor contrast enhancement in the pancreatic tail region of the pancreatic duct. The intraductal mass showed diffusion restriction on magnetic resonance imaging. These imaging findings are consistent with the expansive, smooth-surfaced polypoid tumor of low vascularity and high cellularity that was diagnosed pathologically. Mixed acinar-neuroendocrine carcinomas should be included in the differential diagnosis of intraductal tumors of the pancreas with poor contrast enhancement and diffusion restriction.

Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial.

BACKGROUND: Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS: We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS: A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS: In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

Survival impact of pancreatic resection for metastases in the pancreas: A retrospective multi-center study.

BACKGROUND: Pancreatic metastases from other primary malignancies are rare. There is no clear evidence for a treatment strategy for this condition. The purpose of this study was to assess the clinical outcomes, including prognostic factors for pancreatic resection of metastatic tumors in the pancreas, through a retrospective review. METHODS: Data of 35 patients who underwent pancreatic resection for pancreatic metastasis between 2005 and 2020 in eight Japanese institutions were included in this study. Survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the Cox proportional hazards model. RESULTS: The median follow-up period was 35 months (range, 5-102 months). Median duration from resection for primary tumor to resection for metastatic pancreatic tumor was 10.6 years (range, 0.6-29.2 years). The 3- and 5-year survival rates after resection for metastatic tumors in the pancreas were 89% and 69%, respectively. In contrast, the 3- and 5-year disease-free survival rates after resection for metastatic tumors in the pancreas were 48% and 21%, respectively. Performance status ≥1 at the time of resection for metastatic tumors in the pancreas (HR: 7.56, p = 0.036) and pancreatic metastasis tumor diameter >42 mm (HR: 6.39, p = 0.02) were significant poor prognostic factors only in the overall survival. CONCLUSIONS: The prognosis of pancreatic resection for metastatic tumors in the pancreas is relatively good for selected patients. However, because it is prone to recurrence after radical surgery, it should only be considered in patients with good PS.

Poorly differentiated adenocarcinoma with signet ring cells of the gallbladder producing a high level of alpha-fetoprotein: A case report.

INTRODUCTION: Alpha-fetoprotein (AFP) can become elevated in hepatocellular carcinoma (HCC), yolk sac tumors and other malignant tumors of various organs. Herein, we present a case of AFP-producing gallbladder carcinoma with signet ring cells successfully treated with laparoscopic whole-layer cholecystectomy. PRESENTATION OF CASE: A 69-year-old woman was found to have increased levels of the tumor marker AFP (16.1 to 1474 ng/mL), and an irregularly shaped mass 22 mm in size in the gallbladder at 5 months follow-up after transcatheter arterial chemoembolization and radiofrequency ablation for HCC in segment 3 of the liver. As no additional metastases were detected, we diagnosed the patient with either AFP-producing gallbladder carcinoma (cT2aN0M0, cStage IIa, UICC 8th) or gallbladder metastasis from HCC. Laparoscopic whole-layer cholecystectomy was performed, and histological examination revealed AFP positive poorly differentiated adenocarcinoma with signet ring cells (pT2bN0cM0, pStage IIb, UICC 8th). AFP levels were remarkably decreased after operation (15 ng/mL), and no residual tumors or distant metastases were observed on contrast enhanced computed tomography (CE-CT), indicating that the tumor was an AFP-producing gallbladder carcinoma rather than metastasis of HCC. DISCUSSION: Due to the similar developmental origin of the liver and gallbladder, gallbladder carcinoma could produce AFP in some cases. Considering that AFP is predominantly synthesized during embryogenesis, the status of cellular differentiation would be associated with the ability to synthesize AFP. CONCLUSION: When no lesions except for in the gallbladder can account for elevated AFP levels, clinicians should consider AFP-producing gallbladder carcinoma.

Liver metastases 2 years after resection of a very-low-risk duodenal gastrointestinal stromal tumor: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, but are the most common mesenchymal tumors of the gastrointestinal tract. The risk classification of GISTs is based on the tumor size, mitotic index, tumor site, and presence of tumor rupture. Recurrence in the very-low-risk group is extremely rare. We herein report a case of liver metastases 2 years after resection of a very-low-risk duodenal GIST. CASE PRESENTATION: A 57-year-old woman presented to the hospital for evaluation of melena. Esophagogastroduodenoscopy showed bleeding from the exposed blood vessels at the top of a submucosal tumor approximately 20 mm in size located in the second (descending) part of the duodenum, and the bleeding was controlled with electrocoagulation. A GIST was suspected, and the patient underwent wedge resection of the duodenum. The resected specimen contained a 16- × 12-mm (< 20-mm) white submucosal tumor composed of spindle cells with a mitotic count of 4 per 50 high-power fields, and a histologically negative margin was achieved. Immunochemical analysis revealed positive tumor staining for c-kit protein and alpha-smooth muscle actin and negative staining for CD34, desmin, and S-100 protein. Therefore, the tumor was diagnosed as a very-low-risk duodenal GIST based on the Fletcher classification and modified Fletcher classification (Joensuu classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 11. At the follow-up visit 2 years postoperatively, contrast-enhanced computed tomography revealed liver tumors in S8 and S6 measuring 26 × 24 and 10 × 10 mm, respectively. Both lesions showed peripheral dominant hyperenhancement with hypoenhancement inside, indicating tissue degeneration within the tumors. These imaging findings closely resembled those of the duodenal GIST. Hence, the patient was diagnosed with liver metastases of GIST 2 years postoperatively. She was subsequently started on treatment with 400 mg of imatinib. At the time of this writing (2 months after diagnosis), the patient was clinically well and asymptomatic and was continuing imatinib therapy. CONCLUSIONS: Recurrence of very-low-risk GISTs is extremely rare. Even a small GIST with low mitotic activity can never be considered completely benign, and long-term follow-up is necessary.

"Honeycomb" appearance in large-duct type pancreatic ductal adenocarcinoma: Case report with radiologic-pathologic correlation.

Large-duct type pancreatic ductal adenocarcinoma (PDA) is a rare morphologic variant forming large duct elements. This case report, to our knowledge, is the first report of a large-duct type PDA with a "honeycomb" appearance resembling a serous cystic neoplasm (SCN) on CT and MRI. The patient is an 82-year-old woman who presented with upper abdominal pain. Dynamic contrast-enhanced CT revealed a multilocular cyst with honeycomb loculi, in which the cyst walls showed gradual enhancement. On T2-weighted MRI, the mass displayed inhomogeneous hyperintensity characterized by a honeycomb appearance with irregular and thick hypointense cyst walls. The patient underwent distal pancreatectomy; histopathological diagnosis was large-duct type PDA. Although the imaging features of large-duct type PDA may resemble those of SCN, this distinction between PDA and SCN is important because the treatment options are very different.

Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma.

BACKGROUND: Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients. METHODS: Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated. RESULTS: CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors. CONCLUSION: Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC.

Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study.

BACKGROUND: The aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study. METHODS: Data were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index. RESULTS: Compared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069-1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032-1.736; p = 0.0277). High carbohydrate antigen 19-9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261-2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199-1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001). CONCLUSIONS: Our large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.

Feasibility of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma: a multi-center experience.

PURPOSE: Patients with liver metastasis of head-and-neck carcinoma and esophageal carcinoma are generally not treated with hepatic resection, but there are no established standard treatment methods. We report 11 cases of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma performed at 5 Japanese institutions. METHODS: The subjects of this retrospective analysis were 11 patients who underwent hepatic resection for metastatic liver tumors, originating from head-and-neck carcinoma in 5 and from esophageal cancer in 6, between January, 2010 and March, 2020 RESULTS: There were nine men and two women (median age, 64 years; range 40-72 years). The primary disease was esophageal carcinoma in six patients and pharyngeal carcinoma in five patients. All cancers were squamous cell carcinoma. The time from the initial treatment to the diagnosis of liver metastasis was 15.3 months and the 1-year and 3-year overall survival rates after hepatic resection were 72% and 32%, respectively. The overall and disease-free survival rates after hepatic resection were significantly higher for patients who underwent hepatic resection more than 12 months after the initial treatment than for those who underwent hepatic resection within 12 months after the initial treatment (p = 0.0172 and p = 0.0120, respectively). CONCLUSIONS: Liver resection may prolong the survival of patients with liver metastases controlled for more than 12 months after the initial treatment of head and neck or esophageal carcinoma.

Safety of Combined Division vs Separate Division of the Splenic Vein in Patients Undergoing Distal Pancreatectomy: A Noninferiority Randomized Clinical Trial.

Importance: In distal pancreatectomy (DP), the splenic vein is isolated from the pancreatic parenchyma prior to being ligated and divided to prevent intra-abdominal hemorrhage from the splenic vein stump with pancreatic fistula (PF). Conversely, dissecting the splenic vein with the pancreatic parenchyma is easy and time-saving. Objective: To establish the safety of combined division of the splenic vein compared with separate division of the splenic vein. Design, Setting, and Participants: This study was designed as a multicenter prospective randomized phase 3 trial. All results were analyzed using the modified intent-to-treat set. Patients undergoing DP for pancreatic body and tail tumors were eligible for inclusion. Patients were randomly assigned between August 10, 2016, and July 30, 2019. Interventions: Patients were centrally randomized (1:1) to either separate division of the splenic vein or combined division of the splenic vein. Main Outcomes and Measures: The primary end point was the incidence of grade B/C PF, and the incidence of intra-abdominal hemorrhage was included as one of the secondary end points. Results: A total of 318 patients were randomly assigned, and 2 patients were excluded as ineligible. Of the 316 remaining patients, 150 (50.3%) were male. The modified intent-to-treat population constituted 159 patients (50.3%) in the separate division group and 157 patients (49.7%) in the combined division group. In the modified intent-to-treat set, the proportion of grade B/C PF in the separate division group was 27.1% (42 of 155) vs 28.6% (44 of 154) in the combined division group (adjusted odds ratio, 1.108; 95% CI, 0.847-1.225; P = .047), demonstrating noninferiority of the combined division of the splenic vein against separate division. The incidence of postoperative intra-abdominal hemorrhage in the 2 groups was identical at 1.3%. Conclusions and Relevance: This study demonstrated noninferiority of the combined division of the splenic vein compared with separate division of the splenic vein regarding safety. Thus, isolating the splenic vein from the pancreatic parenchyma is deemed unnecessary. Trial Registration: ClinicalTrials.gov Identifier: NCT02871804.

Impact of Capicua on Pancreatic Cancer Progression.

BACKGROUND: The transcription factor capicua (CIC) regulates mammalian development and homeostasis. Growing evidence shows that CIC suppresses various human cancers by directly repressing the downstream cancer-related target genes. This study investigated the clinical and biologic significance of CIC expression in pancreatic cancer (PC). METHODS: The study reviewed 132 patients with PC who underwent curative resection. The patients were divided into two groups according to CIC immunoreactivity score by immunohistochemistry, and the associations between CIC expression, clinicopathologic characteristics, and postoperative prognosis were investigated. Moreover, the influence of CIC expression on the malignant potential of PC cells was assessed with cell proliferation, motility assays, and use of quantitative real time-polymerase chain reaction and Western blot on the downstream target genes of CIC in knockdown experiments. RESULTS: The low-CIC expression group showed a higher proportion of lymphatic invasion (72.9% vs. 53.1%; p = 0.024), intrapancreatic neural invasion (94.1% vs. 81.3%; p = 0.021), and extrapancreatic plexus invasion (30.9% vs. 7.8%; p = 0.0006) than the high-CIC expression group as well as significantly worse overall survival (p = 0.0002) and recurrence-free survival (p = 0.0041) rates. Low CIC expression was an independent risk factor for poor prognosis (p = 0.038). Pancreatic cancer cells with knockdown CIC significantly enhanced cell motilities and cell cycle progression, promoted expression levels of ETV4 and MMP-9, and induced EMT. CONCLUSIONS: The study elucidated the association of low CIC expression with a poor prognosis for patients with PC and suggested that the CIC-ETV4-MMP-9 axis might control PC progression.

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. RESULTS: The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. CONCLUSIONS: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.

Efficacy of Neoadjuvant Chemotherapy in Distal Pancreatectomy with En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer.

BACKGROUNDS: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an extended surgical procedure for patients with locally advanced cancer of the pancreatic body and tail. Recently, the usability of neoadjuvant chemotherapy (NAC) in pancreatic cancer was reported. The purpose of this study was to clarify the impact of NAC on surgical outcomes and prognosis in DP-CAR patients. METHODS: This study retrospectively reviewed 20 consecutive patients who underwent DP-CAR at a single institution. RESULTS: Eleven of 20 patients (55.0%) received NAC. Their first regimens were gemcitabine (GEM) plus nab-PTX (n = 7, 63.6%), GEM plus S-1 (n = 3, 27.3%), and GEM (n = 1, 9.1%). Although two patients converted to a second regimen, none abandoned NAC due to adverse effects or could not undergo a planned procedure for disease progression. There were no significant differences in intraoperative variables, morbidity, including pancreatic fistula and delayed gastric emptying, and mortality between patients with and without NAC; however, patients with NAC had a significantly lower proportion of arterial invasion (p = 0.025), lymphatic invasion (p < 0.0001), and vascular invasion (p = 0.035). There were no significant differences in the induction rate of adjuvant chemotherapy (p = 0.201). The recurrence-free survival and overall survival rates in patients with NAC were significantly higher than in patients without NAC (p = 0.041 and p = 0.018, respectively). CONCLUSION: DP-CAR following NAC was associated with a preferable prognosis and had no negative effect on surgical outcomes. Therefore, NAC in DP-CAR patients might be a beneficial and safe therapeutic strategy.

A multicenter prospective registration study on laparoscopic pancreatectomy in Japan: report on the assessment of 1,429 patients.

BACKGROUND: Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. METHODS: Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. RESULTS: Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. CONCLUSION: LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.

TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial).

BACKGROUND: In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS). PATIENTS AND METHODS: This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40-60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40-60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS. RESULTS: A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82-1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67-0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups. CONCLUSION: TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1.

Pancreatic cancer arising from the remnant pancreas after pancreatectomy: a multicenter retrospective study by the Kyushu Study Group of Clinical Cancer.

BACKGROUND: After initial pancreatic resection, local recurrence of pancreatic cancer (PC) or new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this retrospective study was to clarify the clinical features and establish a treatment strategy for remnant PC. METHODS: A multicenter retrospective study with the Kyushu Study Group of Clinical Cancer was carried out. Clinical data from 50 patients who developed remnant PC were analyzed. RAS mutation analysis of the initial tumor and of remnant PC was performed in 17 cases. RESULTS: The initial pancreatic resections were performed for 37 invasive ductal carcinomas, and for 13 other tumors. Thirty-seven patients underwent a second pancreatectomy for remnant PC (resected group), while thirteen patients were not operated (unresected group). The median overall survival times were 42.2 months in the resected group and 12.3 months in the unresected group (HR 0.374; 95% CI 0.17-0.83). In RAS mutation analysis, 14 cases had at least 1 missense variant of KRAS, HRAS, or NRAS in the initial pancreatic tumor and/or remnant PC. The same missense variants between the initial tumor and remnant PC were discovered only in KRAS of one patient, and in HRAS of one patient. No case had completely consistent missense variants between the initial tumor and remnant PC. CONCLUSIONS: This study found that repeated pancreatectomy for remnant PC can prolong patient survival, and RAS mutation analysis indicated that many remnant PCs are developed from metachronous multifocal origins.

Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study.

BACKGROUND: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study. METHODS: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis. RESULTS: Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child-Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis. CONCLUSIONS: This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis.

Small pancreatic ductal carcinomas on triple-phase contrast-enhanced computed tomography: enhanced rims and the pathologic correlation.

PURPOSE: To reveal the prevalence of small (≤ 20 mm) pancreatic ductal carcinomas with enhanced rims on triple-phase contrast-enhanced CT and correlate the CT images with the pathologic findings. MATERIALS AND METHODS: Between April 2005 and April 2016, 45 patients underwent preoperative triple-phase contrast-enhanced CT and were pathologically diagnosed with small pancreatic ductal carcinoma. CT images were independently reviewed by two radiologists. The attenuation values of the enhanced rims, internal areas of the tumors, and surrounding pancreatic parenchyma were compared using Mann-Whitney U test. These areas were also correlated with the pathologic findings. Tumor invasiveness was compared between the tumors with and without enhanced rims using Fisher's exact test. RESULTS: Enhanced rims were identified in 18 tumors (40%) by consensus between the two reviewers. The enhanced rims showed significantly higher mean attenuation values compared with the internal areas of the tumors (p < 0.001) and surrounding pancreatic parenchyma (p < 0.0086), and were most clearly visualized on equilibrium phase. The enhanced rims pathologically reflected the abundant fibrotic stroma with cancer cells in all tumors. There was no statistically significant difference in tumor invasiveness between the tumors with and without enhanced rims (anterior peripancreatic invasion, p = 0.137; posterior peripancreatic invasion, p = 0.758; portal vein invasion, p = 0.639; and lymph node metastases, p = 0.359). CONCLUSIONS: Enhanced rims were detected at a rate of 40% in small pancreatic ductal carcinomas and could be an important finding for diagnosis on CT images, but did not suggest a less aggressive nature.