Search

Background: Long-term outcomes and prognostic factors of proton radiotherapy for locally advanced pancreatic cancer (LAPC) in the body and tail are still unknown. The aim of this study was to determine the prognostic factors after proton radiotherapy in a large group of patients with LAPC in the body and tail. Methods: The medical records of 200 patients with LAPC in the body and tail who underwent proton radiotherapy between February 2009 and January 2021 at the Hyogo Ion Beam Medical Center were retrospectively reviewed to identify prognostic factors that contribute to long-term survival. Results: The overall survival rate at 1- and 2-year after PT was 69.6% and 35.4% with a median overall survival of 18.4 months. The 1- and 2-year local progression-free, and progression-free survival rates were 84.3% and 68.0%, and 44.3% and 19.4%, respectively. In multivariate analysis, superior mesenteric artery (SMA) invasion (SMA only invasion vs. celiac artery only invasion; P = 0.049: SMA and celiac artery invasion vs. celiac artery only invasion; P = 0.017), carbohydrate antigen 19-9 (CA 19-9) level ≥ 231.9 U/mL (P = 0.001), anterior peripancreatic invasion (P = 0.006), and incomplete scheduled concurrent chemotherapy (P = 0.009) were statistically significant prognostic factors for overall survival. There was no significant difference in local progression-free survival; however, distant metastasis-free survival was statistically worse in patients with prognostic factors than in those without. Conclusions: Proton radiotherapy for LAPC in the body and tail may be a valuable multidisciplinary treatment option. Patients with SMA invasion, higher pre-proton radiotherapy serum CA 19-9 level, anterior peripancreatic invasion, or incomplete scheduled concurrent chemotherapy had worse overall survival because of worse distant metastasis-free survival, suggesting that distant metastases have a significant impact on overall survival in such patients. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC‐RT) with S‐1 or combination neoadjuvant chemotherapy with gemcitabine and S‐1 (NAC‐GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety. Methods: In the NAC‐RT with S‐1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S‐1. In the NAC‐GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m2 with oral S‐1 for two cycles. The primary endpoint was the 2‐year progression‐free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC‐RT with S‐1 group, and 51 patients were included in the NAC‐GS group in the intention‐to‐treat analysis. The 2‐year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%–56.0%) in the NAC‐RT with S‐1 group and 54.9% (42.8%–65.5%) in the NAC‐GS group (p =.350). The 2‐year overall survival rate was 66.7% in the NAC‐RT with S‐1 group and 72.4% in the NAC‐GS group (p =.300). Although leukopenia and neutropenia rates were significantly higher in the NAC‐GS group than in the NAC‐RT with S‐1 group (p =.023 and p <.001), other adverse events of NAT and postoperative complications were comparable between the two groups. Conclusion: Both NAC‐RT with S‐1 and NAC‐GS are considered promising treatments for resectable pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: The exfoliative cell analyzer, LC‐1000, is medical device that utilizes the principles of flow cytometry, and might provide digital diagnostic information for cytology using a different approach from conventional cytomorphology. In this study, wae examined the usefulness of the LC‐1000 as a diagnostic support system for intraoperative peritoneal lavage cytology and its prognostic impact for pancreatic (PC) and biliary tract cancer (BTC). Methods: Patients with PC and BTC who underwent surgical treatment were included. First, we identified useful indicators of LC‐1000 and established cutoff values to discriminate positive cytology. Next, we verified the validity of these cutoff values. Results: In the test set (n = 48), of the LC‐1000 indicators examined, only MR‐CPIx was significantly different between the negative and positive cytology groups, yielding a cutoff value of 0.86. In the validation set (n = 52), the sensitivity, specificity, positive and negative predictive value of the LC‐1000 for cytology results was 1.0, 0.49, 0.11 and 1.0, respectively. In patients who had undergone radical resection, recurrence‐free survival rate was significantly higher in the LC‐1000 negative group than in the positive group in PC, but not in BTC. Conclusion: The LC‐1000 was useful as digital support system for peritoneal cytology, and it might have potential as a prognostic factor for PC. [ABSTRACT FROM AUTHOR]

Pancreatic cancer primarily arises from microscopic precancerous lesions, such as pancreatic intraepithelial neoplasia (PanIN) and acinar-to-ductal metaplasia (ADM). However, no established method exists for predicting pancreatic precancerous conditions. Endoscopic ultrasonography (EUS) can detect changes in pancreatic parenchymal histology, including fibrosis. This study aimed to elucidate the relationship between pancreatic parenchymal EUS findings and microscopic precancerous lesions. We retrospectively analyzed 114 patients with pancreatobiliary tumors resected between 2010 and 2020 and evaluated the association between pancreatic parenchymal EUS findings and the number of PanIN, ADM, and pancreatic duct gland (PDG). Of the 114 patients, 33 (29.0%), 55 (48.2%), and 26 (22.8%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. Multivariate analyses revealed that abnormal EUS findings were significantly associated with the frequency of PanIN (hyperechoic foci/stranding without lobularity: OR [95% CI] = 2.7 [1.0–7.3], with lobularity: 6.5 [1.9–22.5], Ptrend = 0.01) and ADM (hyperechoic foci/stranding without lobularity: 3.1 [1.1–8.2], with lobularity: 9.7 [2.6–36.3], Ptrend = 0.003) but not with PDG (hyperechoic foci/stranding without lobularity: 2.2 [0.8–5.8], with lobularity: 3.2 [1.0–10.2], Ptrend = 0.12). We observed a trend toward a significantly higher number of precancerous lesions in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Pancreatic parenchymal EUS findings were associated with the increased frequency of PanIN and ADM. Lobularity may help predict the increased number of precancerous lesions. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer. Methods: We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/m2, nab-paclitaxel 90 mg/m2, S-1 60/80/100 mg/day (< 1.25 m2/1.25–1.50 m2/ > 1.5 m2)]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned. Results: From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m2, nab-paclitaxel 90 mg/m2, and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response. Conclusion: We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007). [ABSTRACT FROM AUTHOR]

The high expression of human equilibrative nucleoside transporter‐1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5‐fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S‐1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S‐1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S‐1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S‐1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S‐1 arm. [ABSTRACT FROM AUTHOR]

Objectives The present study was conducted in order to elucidate the relationship between the number of cyst-existing regions and incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN), which currently remains unclear. Methods Subjects comprised 141 patients undergoing resection for IPMN (Non-invasive IPMN (IPMN with low-to high-grade dysplasia): N = 94, invasive IPMN: N = 31, and PDAC concomitant with IPMN: N = 16) between November 2000 and February 2017. A logistic regression analysis was performed to assess the relationship between the number of cyst-existing regions (one region/two or more regions) and incidence of PDAC concomitant with IPMN, adjusted by clinical characteristics. Cyst-existing regions were defined by the number of anatomical parts of the pancreas: the head/body/tail of the pancreas. Results Multiple cyst-existing regions (two or more regions) correlated with the incidence of PDAC concomitant with IPMN (PDAC concomitant with IPMN in one region vs. two or more regions: 3/66 vs. 13/75, multivariable odds ratio [OR] = 4.11, 95% confidence interval [CI] = 1.22 to 18.8, P  = 0.02). In contrast, multiple cyst-existing regions did not correlate with the incidence of IPMN (invasive IPMN in one region vs. two or more regions: 13/66 vs. 18/75, OR = 1.19, 95% CI = 0.52 to 2.76, P  = 0.67). Conclusions Multifocal cysts correlated with the incidence of PDAC concomitant with IPMN, and may be a high-risk factor for PDAC concomitant with IPMN. [ABSTRACT FROM AUTHOR]

Background The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Methods Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. Results Plasma CgA levels ranged 2.9–30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence ( P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total ( P < 0.001) and in G2 patients ( P = 0.020). Conclusions Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence. [ABSTRACT FROM AUTHOR]

This is the response article to correspondence article received for our published article in BMC surgery titled "A prospective single-center protocol for using near-infrared fluorescence imaging with indocyanine green during staging laparoscopy to detect small metastasis from pancreatic cancer". Peter L. Labib, MBChB pointed out the necessity to administer indocyanine green intravenously in separate timing for detection of metastasis in liver and peritoneum. Preoperative injection is suitable to detect hepatic metastasis and intraoperative injection is reported to be well suited to detect peritoneal metastasis. However, we could not find the usefulness of intraoperative injection of indocyanine green for detecting peritoneal metastasis in cases with staging laparoscopy prior to this study. We employed this study protocol with only preoperative injection of indocyanine green to simplify the procedure with consideration of probably more frequent cases of hepatic metastasis that is difficult to detect with white-light imaging than those of peritoneal metastasis. [ABSTRACT FROM AUTHOR]

Background: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC.Methods: Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group.Results: There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was - 10.0% [- 31.7-20.4%].Conclusions: Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT.Trial Registration: UMIN-CTR, UMIN000009172 . Registered 23 October 2012. [ABSTRACT FROM AUTHOR]