Are targeted therapies or immunotherapies effective in metastatic pancreatic adenocarcinoma?

Metastatic pancreatic ductal adenocarcinoma (PDAC) is a major health burden due to its increasing incidence and poor prognosis. PDAC is characterized by a low tumor mutational burden, and its molecular pathogenesis is driven by Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Response to DNA damage through homologous repair is defective in 15% of tumors. Chemotherapy using FOLFIRINOX (folinic acid, fluorouracil, irinotecan, oxaliplatin) or gemcitabine-nab-paclitaxel significantly improves life expectancy, but the median overall survival remains <1 year. Targeted therapies are not efficient in the overall population of patients with metastatic PDAC. Improvements in overall survival or progression-free survival, however, have been demonstrated in subgroups carrying certain mutations. Maintenance therapy with poly-ADP-ribose polymerase (PARP) inhibitors increases progression-free survival in patients with germline mutations in BRCA1/2. Sotorasib shows signs of efficacy against tumors carrying the KRAS G12C mutation, and targeted therapies may also benefit patients with KRAS-wild-type PDAC. Combining targeted therapies with chemotherapy holds promise because of potential synergistic effects. These associations, however, have not yet demonstrated clinical benefit. Checkpoint inhibitors are not effective against metastatic PDAC. Combined immunotherapies attempt to restore their efficacy but have not succeeded yet. Other immunotherapies are emerging such as therapeutic vaccines or chimeric antigen receptor (CAR) T cells, but these strategies remain to be evaluated in large trials. In the future, treatment personalization based on tumor-derived organoids could potentially further improve treatment efficiency.

The choice for the optimal therapy in advanced biliary tract cancers: Chemotherapy, targeted therapies or immunotherapy.

Biliary tract cancers (BTCs) represent a heterogeneous group that includes intrahepatic cholangiocarcinomas (CCAs), perihilar-CCAs or Klatskin tumors, extrahepatic-CCAs, and gallbladder adenocarcinoma. These entities have distinct demographics, risk factors, clinical presentation, and molecular characteristics. In advanced BTCs, the recommendations are mainly supporting a doublet chemotherapy regimen using cisplatin/gemcitabine (CisGem) with a 5-year overall survival rate close to 5% and median overall survival (mOS) of less than a year. The lack of overall efficacy stresses the need for personalized therapies. Recently, whole-genome and transcriptome sequencing highlighted the diversity of BTCs' subtypes. Distinct genetic alterations were retrieved according to the localization, with a high rate of potentially actionable alterations. Targeted therapies and immunotherapy have since then been tested for BTCs, trying to propose a more personalized treatment. This review describes the different therapeutic options, validated and in development, for patients with advanced BTCs.

Hepatitis B virus reactivation in patients with solid tumors receiving systemic anticancer treatment.

BACKGROUND: Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%. However, there is a paucity of data regarding HBV infection management and reactivation risk in patients receiving systemic treatments for solid tumors. DESIGN: We conducted a PubMed search for publications from January 1990 until May 2016 related to HBV reactivation. The search terms were 'hepatitis B reactivation', cross-referenced with 'chemotherapy', then 'hepatitis B' cross-referenced with International Non-proprietary Name of each of the most used chemotherapy drugs in solid tumors. RESULTS: From these data, a grading of HBV reactivation risk and recommendations for management are given for most frequently used anticancer drugs in solid tumors. CONCLUSION: Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption.

Non-surgical access for enteral nutritional: gastrostomy and jejunostomy, technique and results.

Gastrostomy is the most efficient and best tolerated method of prolonged nutritional support. Jejunostomy is used more rarely. Indications for both techniques have increased because of progress in insertion techniques under endoscopic or radiologic guidance. The procedure is simple and rapid, performed under simple sedation with a success rate over 95% for gastrostomy, irrespective of the technique. Mortality directly related to the technique is less than 5%, but associated co-morbidity also explains a more variable but often higher 30-day mortality. Local care and maintenance of the catheter should help avoid most of the late complications such as peristomal leaks, local infection or sepsis of the tunneled catheter in the abdominal wall. The main indications are neurologic swallowing disorders, mechanical dysphagia from ENT or esophageal disease, when the expected duration of enteral nutrition is at least longer than 3 weeks. In patients with severe dementia, no benefit for either nutritional status or quality of life has been demonstrated. In all cases, adequate patient information and careful evaluation of the risk/benefit ratio are capital.

Influence of NaCl reduction and replacement on the growth of Lactobacillus sakei in broth, cooked ham and white sauce.

The growth inhibiting effects of NaCl and selected simple salt replacers (CaCl(2), MgCl(2), KCl and MgSO(4)) on the growth of Lactobacillus sakei were studied in de Man Rogosa Sharpe broth at 7 degrees C over a water phase concentration of 0 to 6.4%. The divalent chloride salts (CaCl(2) in particular) generally had the largest antimicrobial activities at equivalent water phase concentrations, molalities or water activity (a(w)) values. MgSO(4) had not only the least antimicrobial activity but also the smallest a(w) depressing capacity. The results also showed that the antimicrobial effects of CaCl(2) were not fully accounted for by its a(w) depressing effects. Challenge tests performed on cooked ham and white sauce showed that reduction of NaCl levels by 28 and 33%, respectively, had no influence on the microbial stability of these products to L. sakei. Ultimately the study concluded that the microbiological consequences of the full or partial replacement of NaCl on the growth of L. sakei largely depend on the initial level of NaCl, the level of replacement and the nature of the salt replacer used. Altered stability to L. sakei is most likely given a high initial NaCl level, combined with a large level of partial replacement with either CaCl(2) (increased stability) or MgSO(4) (reduced stability) as the replacer.

Tamoxifen retinopathy. A case report.

Tamoxifen is one of the most effective anti-estrogens for breast carcinoma therapy and has been used since 1971. Side effects are not frequent, but some ophthalmologic complications have already been described such as retinopathy, keratopathy and optic neuritis. The authors report a case of retinopathy occurring after a period of 7 years (205 g total doses). They give a review of the literature, with the ophthalmological and functional aspects of the retinopathy.

The ocular ischemic syndrome.

A series of 8 patients (12 eyes) with ocular ischemic syndrome (ocular signs and symptoms due to severe carotid obstructive disease) is presented. Anterior segment signs include rubeosis iridis, neovascular glaucoma and uveitis. Posterior segment manifestations include mid-peripheral intraretinal haemorrhages, narrowed arteries, dilated veins and cotton-wool spots. Fluorescein angiography demonstrates delayed choroidal filling and a prolonged arteriovenous transit time. Pathophysiology, diagnosis, differential diagnosis, treatment and prognosis are briefly discussed.