Durvalumab Combination for Biliary Tract CancerThis trial randomly assigned patients with previously untreated locally advanced or metastatic biliary tract cancer to receive durvalumab or placebo i... AbstractBackgroundPatients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The ...

Objective: To evaluate both the feasibility and efficacy of our combined therapy, which consisted of preoperative chemoradiation, surgery, and postoperative liver perfusion chemotherapy (LPC) for patients with T3 (extended beyond the pancreatic confines) cancer of the pancreas. Summary Background Data: Because of the high incidence of local recurrence and liver metastasis, long-term outcomes for patients after resection of T3-pancreatic cancer are extremely poor. Methods: During the period from 2002 to 2007, 38 patients with T3-pancreatic cancers consented to receive a combination of preoperative chemoradiation, surgery, and postoperative LPC. With the aid of 3D radiation planning, irradiation fields were constructed that included both the primary pancreatic tumor and retropancreatic tissues while taking care to exclude any section of the gastrointestinal tract. The total dose of radiation was 50 Gy (2 Gy × 25 fractions/5 weeks) and was administered in combination with gemcitabine treatments (1000 mg/m²/week × 9/3 months). Preoperative restaging via computerized tomography and intraoperative inspection were used to determine if pancreatectomy was indicated. For respected cases, one catheter was placed into the gastroduodenal artery and another one into the superior mesenteric vein. Postoperatively, 5-FU (125 mg/day × 28 days) was infused via each of these 2 routes. Results: Preoperative chemoradiation was completed for all 38 patients, including 3 patients who required gemcitabine-dose reduction. Seven patients (18%) did not undergo surgical resection because either distant metastases or progressive local tumors had been detected after chemoradiation. The remaining 31 patients (82%) underwent pancreatectomy plus postoperative LPC, without postoperative or in-hospital mortality. The 5-year survival rate after pancreatectomy was 53%, with low incidences of both local recurrence (9%) and liver metastasis (7%). Postoperative histopathologic study revealed a marked degenerative change in cancer tissue, showing negative surgical margins (R0) for 30 patients (96%) and negative nodal involvement for 28 patients (90%). Conclusion: Results of this trial suggest that a combination of preoperative full-dose gemcitabine, concurrent 3D-conformal radiation, surgery, and postoperative LPC is feasible for the treatment of T3-pancreatic cancer. Using the method described in this article, we were able to effectively reduce the incidence of both local and liver recurrence. Therefore, this type of combination therapy seems promising for improving long-term outcomes for patients with T3-cancers of the pancreas. This study is registered with University hospital Medical information Network clinical trials Registry number, UMIN000001804.

Single-cell RNA sequencing (scRNAseq) has been used to assess the intra-tumor heterogeneity and microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, previous knowledge is not fully universalized. Here, we built a single cell atlas of PDAC from six datasets containing over 70 samples and >130,000 cells, and demonstrated its application to the reanalysis of the previous bulk transcriptomic cohorts and inferring cell–cell communications. The cell decomposition of bulk transcriptomics using scRNAseq data showed the cellular heterogeneity of PDAC; moreover, high levels of tumor cells and fibroblasts were indicative of poor-prognosis. Refined tumor subtypes signature indicated the tumor cell dynamics in intra-tumor and their specific regulatory network. We further identified functionally distinct tumor clusters that had close interaction with fibroblast subtypes via different signaling pathways dependent on subtypes. Our analysis provided a reference dataset for PDAC and showed its utility in research on the microenvironment of intra-tumor heterogeneity.