We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC). Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS <53%. Of the 126 patients enrolled from 29 institutions, 125 were deemed eligible. The 1-year OS was 77.4% (95% CI, 64.9-86.0) and 82.5% (95% CI, 70.7-89.9) in the mFOLFIRINOX and GnP arms, respectively. The median PFS was 11.2 (95% CI, 9.9-15.9) and 9.4 months (95% CI, 7.4-12.8) in the mFOLFIRINOX and GnP arms, respectively. The RR and CA19-9 response rate were 30.9% (95% CI, 19.1-44.8) and 57.1% (95% CI, 41.0-72.3) and 42.1% (95% CI 29.1-55.9) and 85.0% (95% CI, 70.2-94.3) in the mFOLFIRINOX and GnP arms, respectively. Grade 3-4 diarrhoea and anorexia were predominant in the mFOLFIRINOX arm. GnP was considered the candidate for a subsequent phase III trial because of its better RR, CA19-9 response, and mild gastrointestinal toxicities. Both regimens displayed higher efficacy in the 1-year survival than in the historical data of gemcitabine monotherapy.

Aim of this review is to propose an acceptable surgical indication for conversion surgery in patients with initially unresectable (UR) pancreatic ductal adenocarcinoma (PDAC) by considering desirable outcomes, including resectability, overall survival (OS), and disease‐free survival (DFS). A comprehensive literature search of PubMed was conducted through July 15, 2019. Eligible studies were those reporting on patients with UR‐PDAC who underwent surgery. We excluded case reports with fewer than 10 patients, insufficient descriptions of survival data, and palliative surgery. When patients with UR‐PDAC with no progression after chemo(radiation) therapy were offered surgical exploration, resectability and median survival time (MST) of those who underwent conversion surgery ranged from 20% to 69% (median, 52%) and from 19.5 to 33 months (median, 21.9 months), respectively. When conversion surgery was carried out in patients with expected margin‐negative resection or with clinical response by Response Evaluation Criteria In Solid Tumors (RECIST), resectability and MST ranged from 18% to 27% (median, 20%) and from 21 to 35.3 months (median, 30 months), respectively. Among patients who underwent conversion surgery based on clinical response and decreased CA19‐9 level after multimodal treatment, resectability and MST ranged from 2% to 24% (median, 4.1%) and from 24.1 to 64 months (median, 36 months), respectively. Decreased CA19‐9 level was a predictor of resectability, OS and DFS by multivariate analysis. In conclusion, decision‐making for conversion surgery based on clinical response and decreased CA19‐9 level after multimodal treatment may be appropriate. With regard to desirable outcomes of OS and DFS, conversion surgery may provide improved survival for patients with initial UR‐PDAC.

Background Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. Methods The frequencies of dose‐limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom‐relieving effects, safety and overall survival. Results The recommended doses of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m² respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0–22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1‐year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3–4 haematological toxicities developed in 35 of 46 patients, whereas non‐haematological adverse events occurred in seven patients. Conclusion Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.

The aim of current study is to verify usefulness of staging laparoscopy (stag-lap) for patient’s selection and to find prognostic factors in patients with radiographically defined locally advanced (RD-LA) pancreatic ductal adenocarcinoma (PDAC). The LA disease was defined as an unresectable disease without distant organ metastasis based on resectability status of NCCN guideline in this study. Stag-lap was performed in 67 patients with RD-LA (2007–2012) which were divided into 4 groups according to metastatic site: group CY (peritoneal fluid or washing cytology positive and without any distant organ metastasis); group P (peritoneal dissemination); group L (liver metastasis); group LA (peritoneal fluid or washing cytology negative and without any distant organ metastasis). Clinical backgrounds, survival curves, and prognostic factors were investigated. There were 16 patients in CY group (24 %), 13 patients in P group (19 %), 10 patients in L group (15 %), and 28 patients in LA group (42 %). Median survival time was 13 months in CY group and 11 months in LA group, which was significantly better than 7 months in P group, respectively (p < 0.05). The rate of emergence of ascites in LA was significantly better than in CY or P groups (p < 0.05). Multivariate analysis showed that the presence of partial response and administration of second-line chemotherapy were significantly independent prognostic factors. The majority of PDAC patients with RD-LA had occult distant organ metastasis. Clinical features and survival curves were different depending on the site of occult distant organ metastasis. Administration of second-line chemotherapy and responsiveness to chemotherapy were associated with favorable prognosis. Staging laparoscopy should be routinely performed in patients with RD-LA PDAC (UMIN000019936).

The aim of this study was to evaluate the effects of active hexose correlated compound (AHCC) intake on immune responses by investigating the number and function of circulating dendritic cells (DCs) in healthy volunteers. Twenty-one healthy volunteers were randomized to receive placebo or AHCC at 3.0 g/day for 4 wk. The number of circulating cluster of differentiation (CD)11c⁺ DCs (DC1) and CD11c⁻ DCs (DC2) were measured. Allogeneic mixed-leukocyte reaction (MLR) was performed. Natural killer (NK) cell activity and the proliferative response of T lymphocytes toward mitogen (phytohemagglutinin [PHA]) were measured. We also measured cytokine production stimulated by lipopolysaccharide [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon gamma-γ, tumor necrosis factor-α). The AHCC group (n = 10) after AHCC intake had a significantly higher number of total DCs compared to that at baseline and values from control subjects (n = 11). The number of DC1s in the AHCC group after intake was significantly higher than at baseline. DC2s in the AHCC group were significantly increased in comparison with controls. The MLR in the AHCC group was significantly increased compared to controls. No significant differences in PHA, NK cell activity, and cytokine production were found between groups. AHCC intake resulted in the increased number of DCs and function of DC1s, which have a role in specific immunity.