Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

The delivery of active agents from organogels is becoming an important topic owing to the possibility of releasing, in a controlled way, lipophilic agents. Controlled release from foods is a topic with increasing relevance owing to the growing industrial interest towards functional or medical foods, i.e. foods containing nutraceutical agents or drugs. Anyway, release properties are related to the rheological properties of organogels, and, therefore, a deep knowledge of their microstructure and physical characteristics is necessary to design carriers with expected release properties. In this work, two low molecular weight gelators (i.e. glycerol monopalmitate, GMP, and glycerol monostearate, GMS) have been investigated using rheology, microscopy and infrared spectroscopy, IR, aiming at understanding the effects of different gelator ratios on organogel properties. It was observed that GMP, within the range of investigated compositions, seems to be more effective in yielding consistent organogels and this effect was related to differences in microstructure with respect to GMS. Their ability to control the oral release of active agents was investigated, in vitro, using a chemotherapeutic drug for adenocarcinoma of the gastrointestinal tract, 5 fluorouracil (5-FU). A physical model based on carrier erosion was used to describe the release data, evidencing a good agreement with experimental values. Among the tested samples it seems that the use of 90% of GMS (over total organogelator content) yields promising results allowing a good partition of the released drug between the gastric and intestinal tracts with the largest value (although lower than 40% of loaded amount) of the total released drug.

ATP-binding cassette member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells (CSCs) in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression. In human-to-mouse CRC tumor xenotransplantation models that exhibited circulating tumor mRNA, we observed that cancer-specific ABCB5 knockdown significantly reduced detection of these transcripts, suggesting that the knockdown inhibited tumor invasiveness. Mechanistically, this effect was associated with inhibition of expression and downstream signaling of AXL receptor tyrosine kinase (AXL), a proinvasive molecule herein shown to be produced by ABCB5-positive CRC cells. Importantly, rescue of AXL expression in ABCB5-knockdown CRC tumor cells restored tumor-specific transcript detection in the peripheral blood of xenograft recipients, indicating that ABCB5 regulates CRC invasiveness, at least in part, by enhancing AXL signaling. Our results implicate ABCB5 as a critical determinant of CRC invasiveness and suggest that ABCB5 blockade might represent a strategy in CRC therapy, even independently of ABCB5's function as an MDR mediator.

Surgical excision is the first-choice treatment for basal cell carcinoma (BCC). Other treatments with topical agents such as 5-fluorouracil or imiquimod have also been suggested for use in superficial BCC (sBCC). Ingenol mebutate (IM) is a novel agent employed in the treatment of superficial actinic keratoses. The drug has been also successfully used in the treatment of sBCC. A case of large nodular BCC (nBCC) of the face in a 100-year-old inoperable woman is described. IM 0.015% gel was applied once daily for three consecutive days. This dose regimen was repeated for seven rounds within 11 months, with complete cure of the tumor. Mild local skin reactions, which were tolerated well, were observed. Selected cases of nBCC could be treated with IM gel, but the optimal concentration of the drug and the standard dose regimen of treatment are yet to be determined.

Objective To describe a possible case of capecitabine-induced myopericarditis in a patient at the Cardio-Oncology Clinic in Calgary, AB. Design A literature search and adverse drug reaction assessment with the Naranjo tool was conducted. Results A 39-year-old male with recurrent locally advanced rectal adenocarcinoma presented two days after adjuvant treatment with capecitabine and oxaliplatin complaining of intermittent, severe interscapular pain. Based on symptoms, laboratory investigations, and imaging, the patient was diagnosed with acute myopericarditis. Management included aspirin, colchicine, and discontinuing adjuvant chemotherapy. A literature review revealed one case report of capecitabine-induced myopericarditis; however, more data were found regarding the cardiotoxicity of fluorouracil, for which capecitabine is a pro-drug. No case reports were found for oxaliplatin. Conclusion Due to the timeline of capecitabine administration, symptom onset, and improvement upon medication discontinuation, capecitabine is the probable cause of the myopericarditis. Although rare, it is important to consider the possibility of myopericarditis in patients receiving a fluoropyrimidine who present with cardiovascular symptoms.

Posterior reversible encephalopathy syndrome (PRES) is one of many causes of status epilepticus (SE). Itis defined classically as a clinical radiographic entity, characterized by presentation of headache, altered mental status, visual disturbances, seizures, and typical neuroradiographic findings of symmetrical white-matter edema. Predisposing conditions include uncontrolled hypertension, eclampsia, and use of chemotherapeu- tic and immunosuppressant agents. Bevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor (VEGF), is used in a combination with FOLFOX [FOL - Folinic acid; F - Fluorouracil (5-FU); OX - Oxaliplatin] as a first-line treatment for patients with metastatic colorectal cancer. We present a case of a 52-year-old male on systemic chemotherapy with FOLFOX and bevacizumab who presented with SE and was diagnosed with PRES. His symptoms resolved with intensive control of blood pressure and discontinuation of chemotherapy. Bevacizumab-induced vasospasm, endothelial and blood-brain-barrier dysfunction, in combination with elevated blood pressure, were likely the underlying mechanism of PRES in our patient.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part II of this series will present both standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.