MicroRNAs: Promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential

Gastric cancer (GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However, response to chemotherapy varies widely, with some patients presenting no or only minor response to treatment. Hence, chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately, to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment, or that allow modification of chemotherapy resistance. MicroRNAs (miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types, and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC. The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics, and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.     

Missed opportunities for diagnosis of female genital mutilation

Objective

To investigate missed opportunities for diagnosing female genital mutilation (FGM) at an obstetrics and gynecology (OB/GYN) department in Switzerland.

Methods

In a retrospective study, we included 129 consecutive women with FGM who attended the FGM outpatient clinic at the Department of Gynecology and Obstetrics at the University Hospitals of Geneva between 2010 and 2012. The medical files of all women who had undergone at least 1 previous gynecologic exam performed by an OB/GYN doctor or a midwife at the study institution were reviewed. The type of FGM reported in the files was considered correct if it corresponded to that reported by the specialized gynecologist at the FGM clinic, according to WHO classification.

Results

In 48 (37.2%) cases, FGM was not mentioned in the medical file. In 34 (26.4%) women, the diagnosis was correct. FGM was identified but erroneously classified in 28 (21.7%) cases. There were no factors (women’s characteristics or FGM type) associated with missed diagnosis.

Conclusion

Opportunities to identify FGM are frequently missed. Measures should be taken to improve FGM diagnosis and care.     

Blood groups,hemoglobin phenotypes and clinical disorders of consanguineous Yansi population

AIM: To study frequency of blood groups, prevalence of sickle-cell anemia trait and glucose-6-phosphate dehydrogenase deficiency (G6PD), among consanguineous Yansi tribe. METHODS: A total of 525 blood samples were collected, of which 256 among the Yansi population, and 269 for the unrelated control group in the Bandundu province of Democratic Republic of Congo. Blood group antigens were determined in the following systems: ABO, Rh, Kell, Duffy, Kidd and MNS. Blood grouping and extended phenotype tests were performed according to standard immunohematological procedures. Spot tests and tandem mass spectrometry were used respectively for the assessment of G6PD and sickle-cell anemia trait. RESULTS: The frequency of ABO phenotypes conformed to the following order O>A>B>AB with notably 62.5%, 23.8%, 12.1% and 1.6% for the Yansi, and 54.6%, 27.5%, 14.1% and 3.7% for the unrelated control group, respectively (P = 0.19). As for the Rh phenotypes, the most frequent were ccD.ee, ccD.Ee, CcD.ee, corresponding to 71.5%, 12.1% and 12.1% for the Yansi, and 70.6%, 15.6% and 8.2%, for the unrelated control group (P = 0.27). The frequency of MN and Ss phenotypes were statistically different between groups (P = 0.0021 and P = 0.0006). G6PD was observed in 11.3% of subjects in the Yansi group, and in 12.4% of controls (P = 0.74). The sickle-cell anemia trait was present in 22.4% of Yansi subjects and 17.8% in the control group (P = 0.24). Miscarriages and deaths in young age were more common among Yansi people. CONCLUSION: This study shows a significant difference in MNS blood group distribution between the Yansi tribe and a control population. The distribution of other blood groups and the prevalence of hemoglobinopathies did not differ in the Yansi tribe.     

Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein

In this study, we investigated in dogs the immunogenicity and protective immunity against Leishmania (Leishmania) chagasi infection induced by vaccination with a formulation containing the recombinant A2 protein, an amastigote specific antigen, and saponin. Vaccinated animals produced significantly increased levels of total IgG and IgG2, but not IgG1 anti-A2 antibodies, and remained negative in conventional leishmaniasis serodiagnostic methods. Significantly increased IFN-gamma and low IL-10 levels were detected in vaccinated animals before and after challenge, as compared to control animals. Importantly, while the symptoms onset appeared as early as three months after infection in most control dogs, 14 months after challenge, 5 out of 7 vaccinated dogs remained asymptomatic. Therefore, immunization with rA2 antigen was immunogenic and induced partial protection in dogs, and allowed the serological differentiation between vaccinated and infected animals, an important requirement for a canine visceral leishmaniasis (CVL) vaccine.     

Blue light-filter intraocular lenses in vitrectomy combined with cataract surgery: results of a randomized controlled clinical trial

PURPOSE: To evaluate the effect of the blue light-filter intraocular lenses (IOLs) in vitrectomy combined with cataract surgery, focusing on the surgeon's ability to perform specific vitreoretinal procedures and on the patients' outcome. DESIGN: Randomized clinical trial. METHODS: Sixty patients, recruited from our outpatient department, were assigned randomly to receive an ultraviolet-filter IOL (clear IOL group) or a blue light-filter IOL (yellow IOL group) combined with a vitreoretinal procedure. Main outcome measures were intraoperative conditions for the surgeon and the functional outcome. Second outcome measures were complication rates and vitreoretinal diagnoses. RESULTS: The questionnaire responses showed that the blue light-filter IOLs did not represent an impediment to vitreoretinal surgery (P>.05). No intraoperative complications were encountered in either group. Patients in both IOL groups showed comparable functional results with respect to visual acuity, contrast sensitivity, color vision, and glare effect (P>.05). The functional outcome was influenced significantly by the vitreoretinal diagnosis (P<.01). CONCLUSIONS: With the possible advantage of macular protection and no intraoperative or functional disadvantage, the routine use of the blue light-filter IOL in combined surgery can be recommended.     

CFC1 gene involvement in biliary atresia with polysplenia syndrome

The present report describes CFC1 gene analysis in 10 patients with polysplenia syndrome. The heterozygous transition c.433G>A (Ala145Thr) located in exon 5 was identified in 5 patients, with a twice-higher frequency than in control patients. These results suggest that heterozygous CFC1 mutation may represent a genetic predisposition to biliary atresia splenic malformation syndrome.     

Local lymph node micrometastasis in a patient with negative sentinel lymph node biopsies after lymphatic mapping with wide local excision of primary melanoma on the head/neck area

Sentinel lymph node biopsy is widely accepted as a staging procedure for patients with cutaneous melanoma who are at risk for metastases. The complex lymphatic drainage pattern on the head and neck makes sentinel lymph node mapping more challenging compared with other sites. Here, we report a patient who underwent reexcision of the primary tumor site with lymphatic mapping on the right posterior auricular area. Four sentinel nodes were negative for melanoma metastasis; however, step sectioning of the wide local excision of the primary tumor site revealed a small lymph node with histopathologic detection of micrometastasis. Our findings highlight the importance of a careful histopathologic approach that may have prognostic impact on outcome and survival.     

A Randomized Comparison of Chloroquine versus Dihydroartemisinin–Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam

A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin–piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan–Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0–37%), thus establishing non-inferiority of DHA-PPQ. Fever clearance time (median 24 versus 12 hours, P = 0.02), parasite clearance time (median 36 versus 18 hours, P < 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours, P < 0.001) were all significantly shorter in the DHA-PPQ arm. All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward, with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients. Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam, but DHA-PPQ provides more rapid symptomatic and parasitological recovery.