Daylight Saving Time and Automobile Accidents: Evidence From Chile.

Under the evidence that the Daylight Saving Time (DST) regime does not accomplish its primary goal of saving energy, I analyze one of the main side effects, automobile accidents in Chile between 2002 and 2018. I use a Regression Discontinuity Design (RDD) exploiting the discrete nature of the transition into DST and a Difference-in-Difference (DID) approach, taking advantage of the changes in dates that the policy starts and ends over the years. I find a 2.

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial.

Purpose: The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria.

Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study.

Background: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis.

Methods: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries.

Clinical experience with pemigatinib for previously treated metastatic cholangiocarcinoma: practical considerations from clinical cases.

The management of advanced cholangiocarcinoma (CCA) is challenging. In patients with advanced CCA, gemcitabine/cisplatin combination is the standard frontline chemotherapy, with 5-fluorouracil-based regimens preserved for subsequent lines; however, the expected survival is poor. Pemigatinib was approved for locally advanced or metastatic CCA with fusions or rearrangement.

Metastatic breast cancer and monoclonal gammopathy of undetermined significance resembling multiple myeloma.

Radiological evidence of lytic bone lesions has a wide differential diagnosis including metastatic bone disease, multiple myeloma, primary bone cancers and infection. Here, we present the case of a woman in her 80s found to have lytic bone lesions associated with an IgA paraproteinaemia who was thus presumed to have a diagnosis of multiple myeloma. However, bone marrow biopsy results were indicative of monoclonal gammopathy of undetermined significance.

Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial.

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer.

ULBP1 Is Elevated in Human Hepatocellular Carcinoma and Predicts Outcome.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide, and despite recent immunotherapeutic advances there remains a need for improved diagnostic, prognostic, and therapeutic tools. UL-16 binding protein 1 (ULBP1) is a ligand of the activatory receptor Natural Killer cell Group 2 receptor D (NKG2D) and is found as a cell-surface protein on some malignant cells including on human hepatocellular carcinomas. We aimed to explore the biological and clinical significance of NKG2D ligands in the circulation of patients with HCC.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

Background: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.

Methods: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP.

Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial.

Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.

Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.

Design, Setting, And Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study.

Metastatic bone disease from an occult renal primary.

We report a rare presentation of metastatic renal cell carcinoma (RCC) in a 71-year-old man who presented with persistent shoulder pain. MRI revealed widespread lytic lesions within the bones suggestive of metastatic disease but extensive imaging including CT chest, abdomen and pelvis with contrast and fluorodeoxyglucose-positron emission tomography did not identify a primary cancer. The diagnosis was ultimately made from a targeted bone and subsequently targeted liver biopsy, whereby immunohistochemistry was consistent with metastatic RCC (mRCC).

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.

Background: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.

Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

Background: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice.

Methods: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder.

Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours.

Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET.

Neurological symptoms from a brain metastasis as the first presentation of colorectal cancer.

A 63-year-old man, a wheelchair user, from primary progressive multiple sclerosis (MS), presented with an episode of expressive dysphasia and confusion. Cerebral imaging revealed a solitary cerebral mass that was radiologically felt to be a primary brain tumour, but a brain biopsy demonstrated an adenocarcinoma in keeping with brain metastasis. Further immunohistochemistry suggested a probable colorectal primary.

Peritoneal lymphomatosis: a rare presentation of follicular lymphoma mimicking peritoneal carcinomatosis.

Patients presenting with ascites associated with peritoneal disease have a wide differential diagnosis including both malignant and non-malignant related causes. We present the unusual case of a patient, clinically deteriorating, whose malignant peritoneal disease was due to an underlying follicular lymphoma. An urgent staging CT scan followed by a peritoneal biopsy allowed the patient to start chemotherapy within days of acute presentation to the hospital.

Oxaliplatin/5-fluorouracil in advanced hepatocellular carcinoma: case report and single-center retrospective review.

Aims: Sorafenib is the only standard therapy for advanced hepatocellular carcinoma, but has a low response rate. Leucovorin and oxaliplatin (FOLFOX) has a superior response rate versus doxorubicin among Asian sorafenib-naive patients. We aimed to retrospectively review the outcome of 20 consecutive patients treated with FOLFOX at a single European center.