Modified docetaxel,cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study

Aim: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC).

Methods: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2–6 cycles of mDCF chemotherapy which consisted of docetaxel 60?mg/m² intravenously (IV) on day 1, cisplatin 60?mg/m² IV on day 1, and 5-fluorouracil 600?mg/m² IV for 5 days of continuous infusion, with cycles repeated every 21 days.

Results: The most common grade 3–4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3–8.6) and 11.5 (95% CI: 9.4–13.7) months, respectively.

Conclusions: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.     

Detection of metabolites of the new synthetic cannabinoid CUMYL‐4CN‐BINACA in authentic urine samples and human liver microsomes using high‐resolution mass spectrometry

CUMYL‐4CN‐BINACA(1‐(4‐cyanobutyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H–indazole‐3‐carboxamide) is a recently introduced indazole‐3‐carboxamide‐type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine, Istanbul Narcotics Department, in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL‐4CN‐BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n = 80). In this study, 5 μM CUMYL‐4CN‐BINACA was incubated with human liver microsomes (HLMs) for up to 3 hours, and metabolites were identified using liquid chromatography–high‐resolution mass spectrometry (LC–HRMS). Less than 21% of the CUMYL‐4CN‐BINACA parent compound remained after 3 hours of incubation. We identified 18 metabolites that were formed via monohydroxylation, dealkylation, oxidative decyanation to aldehyde, alcohol, and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL‐4CN‐BINACA was not detected; CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was major metabolite after β‐glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL‐4CN‐BINACA N‐butanoic acid), M8 and M11 (hydroxylcumyl CUMYL‐4CN‐BINACA) as urinary marker metabolites to confirm CUMYL‐4CN‐BINACA intake.     

A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second- Line Therapy in Patients with Advanced Gastric Cancer

Objective: We aimed to evaluate the effectiveness of an mEOX (modified epirubicin, oxaliplatin plus capecitabine) regimen as second line therapy after failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods: Gastic cancer patients for whom first-line therapy was unsuccessful and who subsequently received mEOX (epirubicin 50 mg/ m2 on day 1, oxaliplatin 85 mg/m² day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every 3 weeks until disease progression or unacceptable toxicity, were retrospectively analyzed. Results: The study population comprised 129 cases with a median age of 55 years (range= 27-78), the majority being male (76 %). Most (75.2%) had ≥ 2 sites of metastasis. The median number of chemotherapy courses was five (range= 2–9). Forty-nine achieved a partial response and 33 showed stable disease, resulting in a ORR (overall response rate) of 38% and a DCR (disease control rate) of 63.6%. The most frequent features of grade 3-4 hematological and non-hematological toxicity were neutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients suffered death due to toxicity. The median PFS was 4.7 months (95% CI, 4.1–5.3) and the OS was 7.4 months (95% CI, 6.3–8.5). On multivariate analysis, age ≥ 60 years and ECOG performance status (0-1) were independent prognostic factors affecting PFS and OS. Conslusions: In advanced gastric cancer patients, who progress after first line chemotherapy and have an ECOG performance status of 0-1, mEOX is a well tolerated triple regimen associated with a promising OS and PFS.     

Single-Port Laparoscopic Surgery Technique in Children Using Glove-Port and Conventional Rigid Instruments

Single-port laparoscopic surgery (SPLS) is a surgical technique with many advantages over conventional laparoscopy. Its range of indications has expanded alongside the development of its unique tools and equipment. We are able to safely perform SPLS with the low-cost glove-port method without need of any specially developed SPLS port or the TriPort Access System. For this study, the files of patients who underwent laparoscopic surgeries performed between the dates of January 2013 and December 2014 at our clinic were reviewed. Umbilical access single-port abdominal surgeries which were performed using glove-port technique were included in the study. Two hundred nineteen patients who underwent SPLS surgery were included in the study. Of these patients, 158 (72.1%) were male and 61 (27.8%) were females. 58.4% of the cases were appendectomies (n = 128), 20% were orchidopexies (n = 44), 8.6% were orchiectomies (n = 19), 5.4% were ovarian cyst excisions (n = 12), 3.6% were varicocelectomies (n = 8), 2.2% were peritoneal dialysis catheter placements (n = 5), and 1.3% were nephroureterectomies (n = 3). In 67 cases (30.4%), Kirschner wire was used to eliminate the need for a second port. The study concludes that glove-port SPLS, which can readily be performed using conventional tools and Kirschner wire rather than expensive specially developed instruments, is a preferable technique because it is reliable, more cost-effective, and results in a scarless recovery.     

Morgagni’s Hernia: Analysis of 21 Patients with Our Clinical Experience in Diagnosis and Treatment

A Morgagni’s hernia is a congenital defect found in the anterior aspect of the diaphragm between the costal and the sternal portions of this muscle. This defect is also referred to as the space of Larrey. It has been reported that 70% of patients with Morgagni’s hernia are female, 90% of the hernias are right-sided, and 92% of the hernias have hernia sacs. This type of hernia is a rare clinical entity and accounts for 3% of all surgically treated diaphragmatic hernias. There are no large retrospective or prospective studies on this topic. This type of hernia is a rare type among adults without a well-described prevalence and without well-established definitive management strategies. There are also few clinical reports about this clinical entity and its surgical treatment. We treated 21 patients with Morgagni’s hernia in a 12-year period, and we report our experience while discussing the surgical treatment of this disease. We performed a retrospective review of the 21 patients who were operated between 2003 and 2015. These patients had undergone surgical repair of Morgagni’s hernia. For each subject, demographic data, symptoms of presentation, physical examination findings, preoperative imaging studies and diagnosis, and surgical procedures were documented. Location of the hernia sac and its contents, postoperative complications, and duration of hospital stay were recorded and evaluated. Twelve patients were females and nine were males. The mean age of patients was 63.85 years. Dyspnea was the most prominent symptom in our patients. Morgagni’s hernias were located on the right side in 19 patients and on the left side in 2 patients. Chest X-ray in 10 patients and abdominal computerized tomography in 17 patients were the major diagnostic tools. Four patients were operated as emergency while others underwent elective surgery (17 patients). Twelve patients were operated with laparoscopy and the remaining nine were operated with the conventional open abdominal technique. Hernia sacs were observed in all of the patients and removed except in four of them. The omentum and the transverse colon were the most commonly seen organs in hernia sacs. Hernia defects were repaired with primary sutures in four patients (all open cases) and primary closure supported with mesh in six patients (four laparoscopic, two open cases). In the remaining 11 patients, hernia defects were closed with synthetic meshes (eight laparoscopic, three open cases). Mean postoperative hospital stay was 9.8 days. No recurrence was observed in any patients. Only one of our patients died during follow-up. In Morgagni’s hernias, surgical intervention is necessary as the hernia may cause complications such as strangulation of the colon or intestines. A laparoscopic approach has increased its popularity in recent years because of the well-known advantages of laparoscopy.     

The reliability of hip scoring systems for total hip arthroplasty candidates: assessment by physical therapists

OBJECTIVE: Hip rating systems have been widely used in assessing severity of hip dysfunction but no uniform method has emerged. The current study was performed to determine the interobserver reliability of five different hip scores on patients with coxarthrosis. DESIGN: Test reliability among physical therapists for five commonly used hip scores. SUBJECTS: Thirty-five patients (48 hips) who had coxarthrosis and who were candidates for total hip arthroplasty were included in the study. METHODS: Patients were evaluated preoperatively by three physical therapists using five different hip rating systems; the Harris Hip Score, the Iowa Hip Score, the Charnley Hip Score, the Merle d'Aubigne Hip Score and the American Academy of Orthopaedic Surgeons' Hip Score. RESULTS: The average age of the patients was 58.8 +/- 2.2 years (range 28-76 years). For all scores, an excellent interobserver reliability between the physical therapists were found (kappa = 0.77-0.95). The best correlation between first and second observer was on Harris Hip Score (kappa = 0.91), between second and third was on Merle d'Aubigne Hip Score (kappa = 0.95) and between first and third was on Iowa Hip Score (kappa = 0.87). CONCLUSION: There was an excellent interobserver reliability for all hip scores between the physical therapists, suggesting that all these hip scores are suitable for use by physical therapists.     

Therapeutic options for pneumococcal pneumonia in Turkey

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Streptococcus pneumoniae continues to be the most important causative agent in CAP. OBJECTIVE: This article reviews options for the empiric treatment of pneumococcal pneumonia in Turkey based on local epidemiologic data. METHODS: This was a retrospective review of studies evaluating antimicrobial susceptibility patterns among clinical isolates of S pneumoniae in Turkey from 2000 onward. Relevant studies were identified through literature searches of both Turkish (Ulakbim and Pleksus) and international (MEDLINE) databases using the search terms S pneumoniae and Turkey. Only antibiotics likely to be used in pneumococcal pneumonia were evaluated. The minimum concentration required to inhibit 90% of isolates (MIC(90)) for each antibiotic was obtained by averaging all reported values to arrive at a single value for the entire country. RESULTS: The MIC(90) for penicillin was 1 g/mL; among all isolates of S pneumoniae, 6.4% were penicillin resistant and 30.9% showed intermediate susceptibility. The MIC(90)s and overall rates of resistance (combined intermediate susceptibility and resistance) for the other antibiotics studied were as follows: cefaclor, 4 microg/mL (26.3%); cefuroxime, 2 microg/mL (15.4%); ceftriaxone, 0.25 microg/mL (0.75%); imipenem, 0.06 microg/mL (0%); erythromycin, 2 microg/mL (13.9%); clarithromycin, 2 microg/mL (13.7%); azithromycin, 2 microg/mL (13.8%); telithromycin, 0.06 microg/mL (no published breakpoints); trimethoprim-sulfamethoxazole, 4 microg/mL (63.8%); tetracycline, 16 microg/mL (24.6%); ciprofloxacin, 2 microg/mL (no published breakpoints); ofloxacin, 2 microg/mL (4%); levofloxacin, 1 microg/mL (0%); gemifloxacin, 0.06 microg/mL (no published breakpoints); and moxifloxacin, 0.06 microg/mL (0%). Penicillin G, at standard parenteral doses, has been shown to achieve concentrations above the MIC for >40% to 100% of the dosing interval, depending on the MIC of the isolate. Based on pharmacodynamic studies, the MIC(90) for penicillin in Turkey should easily be exceeded with the use of penicillin G 3 mU QID. In vitro, susceptibility is generally greater to amoxicillin than to penicillin, with average amoxicillin MIC values approximately 1 dilution lower than those for penicillin. Amoxicillin's better pharmacodynamic/pharmacokinetic properties relative to penicillin make it a reasonable option for the treatment of CAP. In pharmacodynamic studies, amoxicillin 1 g TID achieved and maintained serum concentrations of 2 to 4 microg/mL for at least 40% of the dosing interval. A new formulation of amoxicillin/clavulanate given 2000/125 mg BID is expected to eradicate isolates of S pneumoniae at an amoxicillin MIC < or = 4 microg/mL. CONCLUSIONS: Based on data from Turkish surveillance studies performed from 2000 onward, high-dose parenteral penicillin G and parenteral/oral amoxicillin may be initial choices for the empiric treatment of uncomplicated pneumococcal pneumonia in Turkey. If these agents cannot be used for any reason, other options include parenteral cefuroxime, ceftriaxone, cefotaxime, newer quinolones, macrolides, and telithromycin. Due to elevated rates of resistance in Turkey, trimethoprim-sulfamethoxazole and tetracyclines are not recommended for empiric use in these infections.     

Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis

Aim. Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t‐DCS) is a non‐invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t‐DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t‐DCS on seizures in Rasmussen encephalitis and to clarify its safety. Methods. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non‐sham stimulations), and finally sham stimulation with two‐month intervals, respectively. Three patients received classic (DC) cathodal t‐DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60‐second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm × 50 mm wet sponge electrodes with 2‐mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30‐minute stimulation period. Results. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t‐DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Conclusion. Both classic and modulated cathodal t‐DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.