Protective Role of Bilberry Extract Against Cisplatin Induced Ototoxicity in Rats

To investigate the potential preventive effect of bilberry extract in cisplatin-induced ototoxicity. Thirty-five 3–3.5-month healthy adult female Sprague–Dawley rats were randomly divided into three groups and treated as follows: Both, group 1 (n = 10) and group 2 (n = 15) subjects received a single dose of 12 mg/kg cisplatin intraperitoneally; while in group 2, bilberry extract was also administered via gavage feeding for 15 days. Group 3 (n = 10), received no cisplatin or bilberry extract. Baseline distortion product otoacoustic emissions testing were performed in all subjects prior to administration of any medication. The test was repeated at 15th day following administration of any medication. The distortion product otoacoustic emissions were evaluated at 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 12 kHz. Histopathological changes in the cochlea of rats were observed by light microscopy. There was no statistically significant difference in apical turn between three groups but there was a statistically significant difference in basal and mid turn external ciliated cells number. Stria vascularis changes were statistically significant between three groups. The median score for stria vascularis injury and spiral ganglion cells changes were significantly greater in group 1 than in group 2. The initial distortion product otoacoustic emissions measurement results gave similar statistically insignificant values in the three groups (p > 0.05). In contrast to initial measurements statistically significant differences were recorded between day 0 and 15 otoacoustic thresholds (p < 0.05). Bilberry extract group had a significantly higher DP-gram except for 1.5 and 2 kHz frequencies when compared to cisplatin group. The analyses of the results revealed statistically significant differences between two groups (p < 0.05), suggesting that bilberry extract had shown a protective effect against cisplatin ototoxicity. The results of our study revealed that treatment with bilberry extract affords significant protection to the cochlea from cisplatin toxicity and thus, oral experimental dose of bilberry extract administration may have a protective effect against cisplatin ototoxicity in rats.     

Ototoxicity of Different Concentrations Povidone-Iodine Solution Applied to the Middle Ear Cavity of Rats

To investigate the ototoxic effects of different concentrations of povidone-iodine solutions applied to the middle ear cavity of rats using distortion product otoacoustic emissions. 24 healthy 3–3.5-month-old adult female Sprague-Dawley rats were randomly divided into three groups. The group A (n = 8 ears) received 5 % povidone-iodine solution to the right ear, the group B (n = 8 ears) received 7.5 % povidone-iodine solution to the right ear and the group C (n = 8 ears) received 10 % povidone-iodine solution to the right ear. All animals received saline solution to the left ear as a control (n = 24 ears). The animals were tested before, 1 and 10 days after solutions administration to the middle ear. The resulting distortion product otoacoustic emissions were evaluated at 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 12 kHz. Statistically significant reductions in DP-gram amplitudes were noted at high frequencies (7, 8, 10, 12 kHz) in the group A at day 1 but this effect return at day 10. In group B and group C statistically significant differences were recorded for low and high frequencies (1.5, 2, 7, 8, 10, 12 kHz) according to the control group at day 1 and 10. 7.5 and 10 % povidone-iodine showed a significant ototoxic effect on day 1 and 10. But this toxic effect could not be elicited in 5 % povidone-iodine group on day 10. The present study revealed that commercially available high concentration povidone-iodine solution may cause significant ototoxic effects when applied topically through a perforated ear drum in rats. Based on results of this experiment, high concentration povidone-iodine solutions should not be used for preoperative surgical site cleansing for otologic surgery.     

Comparison of the Transient Evoked Otoacoustic Emissions (TEOAEs) and Distortion Products Otoacoustic Emissions (DPOAEs) in Normal Hearing Subjects With and Without Tinnitus

The aim of this study was to investigate the possible role of cochlear outer hair cell function with TEOAE and DPOAE tests in patients with normal hearing and tinnitus. 25 tinnitus patients with normal hearing sensitivity selected as study group. Control group consist of 50 normal hearing subjects without tinnitus. All subjects had thresholds below 25 dBHL at frequencies 250–8,000 Hz, tympanogram type A and normal acoustic reflex thresholds. TEOAE were recorded with click stimulus at 80 dB SPL at 1,000, 2,000, 3,000 and 4000 Hz. DPOAE were measured at frequencies 1,000–8,000 Hz and intensity of L1 55 dB SPL and L2 65 dB SPL. Amplitude of DPOAE and TEOAE were decreased in all frequencies in study group. There was significant difference regarding prevalence abnormal TEOAE and DPOAE between study group and control group. There was relationship between dysfunction of outer hair cells and tinnitus in subjects with normal hearing.     

Cochlear Implantation in Children with Anomalous Cochleovestibular Anatomy: Our Experience

To report operative findings, postoperative course, and postimplantation performance in patients with cochlear malformations who underwent cochlear implantation. Seventeen patients with malformations which included enlarged vestibular aqueduct (n = 6), Mondini’s dysplasia (n = 5) common cavity deformity (n = 3) and incomplete partition type 2 (n = 3) underwent cochlear implantation with Nucleus 22 straight array device at our center. Operative findings described facial nerve anatomy and cerebrospinal fluid leak. Standard tests of speech perception were used to evaluate the postoperative performance for each subject. Operative findings included cerebrospinal fluid leak (thirteen patients) all of which were repaired successfully with graft. None had abnormal facial nerve anatomy. No surgical complications occurred. All the patients except two with common cavity had complete insertion. Electrode thresholds and discomfort levels were variable for several months after implantation. All patients demonstrated improved performance after implantation. Patients with enlarged vestibular aqueduct fared better than patients with other inner ear malformations. Cochlear implantation can be a successful method of rehabilitation in patients with congenital deafness who have cochlear malformations.     

A Phase II Study to Determine the Safety and Efficacy of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase (IDO) Enzyme INCB024360 in Patients with Myelodysplastic Syndromes

Background

INCB024360 is an oral inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the degradation of tryptophan to kynurenine. Preclinical data suggest that IDO1 inhibition by INCB024360 will increase T cell proliferation, and decrease T regulatory cells and myeloid derived suppressor cells suppressive activity. We conducted a phase II study to explore activity and pharmacodynamics of INCB024360 in patients with myelodysplastic syndromes.

Correlation of Radiological and Endoscopic Findings in Patients Presenting with Dysphagia

Dysphagia is a common symptom with diverse etiology in otolaryngology. In the present study clinicopathological, radiological and endoscopic evaluation of patients was done in a tertiary care hospital in patients presenting with dysphagia. A prospective nonrandomized observational study was carried out on total of 80 cases having dysphagia during March 2015 to August 2016. In the present study, out of 80 patients, youngest case was a three years old child while oldest case was an 85 years old female. The mean age was 48.3 ± 20.3 years. The majority of cases were in age group 41–59 years (35%). Male to female ratio was 2.33:1. The mean duration of illness was 15.44 weeks. 15% of patients had absolute dysphagia. For detecting the lesion, Barium swallow study (BSS) showed a total sensitivity of 49.05% (n = 53), Computerised Tomography (CT) showed a total sensitivity of 85.70% (n = 49), plain skiagram neck & chest showed a total sensitivity of 88.88% (n = 9) and endoscopy was the most sensitive test overall as it showed a total sensitivity of 98.75% (n = 80). No complications were reported with either rigid or flexible endoscopy. Dysphagia is a common presenting complaint in otolaryngology with cases coming directly or being referred from other specialities. Males are more commonly affected than females and incidence of malignancy increases with age. Endoscopy can become the first screening test in dysphagia due to its high sensitivity and low risk of complications, with radiological tests being done in an adjunct manner.     

Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan

Background

The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC).

Diffusion-weighted imaging reflects pathological therapeutic response and relapse in breast cancer

Background

Conventional imaging does not always accurately depict the pathological response to neoadjuvant chemotherapy (NAC). Diffusion-weighted imaging (DWI) may provide additional insight into the chemotherapeutic effect. This study assessed whether the apparent diffusion coefficient (ADC) correlated with pathological outcome and prognosis in breast cancer patients receiving NAC.

Methods

Fifty-six patients with locally advanced breast cancer received surgery after NAC. Dynamic contrast-enhanced (DCE) and DWI were performed before and after NAC. The pathological response was classified into five categories from no response to complete response according to amount of residual cancer. The correlation between ADC and postoperative pathologic and prognostic outcome was assessed.

Results

The distribution of the pathological response classification was as follows: no response, 3 cases; mild response, 22 cases; moderate response, 12 cases; marked response, 11 cases; complete response, 8 cases. ADC after NAC correlated with pathological response, but ADC before NAC did not. The change in ADC after chemotherapy had better correlation coefficient (r = 0.67) than change in size (r = 0.58) and ADC after NAC (r = 0.64). Although the group with larger change of tumor size showed only marginal significance compared with the smaller change group (p = 0.089), the group with higher change of ADC showed significantly better prognosis than the lower one (p = 0.038).

Conclusions

Change in ADC after chemotherapy better correlated with pathological outcome and prognosis than change in tumor size. DWI has potential in evaluating the pathological outcome of NAC in breast cancer patients.     

Survival outcome and reduction rate of Ki-67 between pre- and post-neoadjuvant chemotherapy in breast cancer patients with non-pCR

The research question of this investigation is whether the reduction rate of Ki-67 after neoadjuvant chemotherapy (NAC) could indicate a survival in patients with non-pCR. A total of 455 patients had received NAC, and subsequent surgery was analyzed retrospectively. Patients with non-pCR were divided into three subgroups according to Ki-67 change: High-reduction (the absolute value of Ki-67 was reduced by >80 % compared with that prior to NAC), Low-reduction (the absolute value of Ki-67 was reduced by 0–80 % compared with that prior to NAC), and Increase group (the absolute value of Ki-67 was increased compared with that prior to NAC). The relapse-free survival (RFS) rates were compared among subgroups. pCR was achieved in 93 patients (20.4 %). In patients with non-pCR, the median reduction rate of Ki-67 was 60 %. A total of 15 % of patients were in the High-reduction, 63 % in the Low-reduction, and 22 % in the Increase group. The median follow-up period was 64.5 months. The 5-year RFS rates among the three groups were significantly different (p < 0.0001), and the differences were also observed in the HER2 (p = 0.033), triple-negative (p = 0.034), and luminal-like subtypes (p = 0.001). Patients in the High-reduction group showed comparable RFS to that of patients with pCR (p = 0.363). In patients with non-pCR, the reduction rate of Ki-67 after NAC significantly predicted RFS regardless of cancer subtypes. Therefore, patients who are non-pCR but who achieve a high reduction of Ki-67 can be expected to have a favorable prognosis similar to that of patients with pCR.     

Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience

Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor’s sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2–16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3–4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.     

The impact of acute inflammation on progression and metastasis in pancreatic cancer animal model

Background

The impact of acute inflammation on cancer is unclear. Therefore, we evaluated the impact of acute inflammation on cancer progression in an animal model concerning morphological change as well as molecular features.

Comparative Efficacy and Safety of Various Anti-Microbials in Patients of Acute Rhinosinusitis at Tertiary-Care Hospital in Uttarakhand (UK)

To compare the efficacy of gatifloxacin, azithromycin with amoxicillin as positive control for the treatment of Acute rhinosinusitis (ARS). To monitor adverse drug reaction profile of amoxicillin, azithromycin and gatifloxacin in patient of ARS. An open randomized trial of comparative efficacy and safety of amoxicillin, azithromycin and gatifloxacin in patients with ARS. Patients were randomized into three groups as under: group 1: patients on oral amoxicillin 500 mg TDS for 10 days; group 2: patients on oral azithromycin 500 mg OD for 5 days; group 3: patients on oral gatifloxacin 400 mg OD for 10 days. Patients were evaluated for signs and symptoms at day 1, day 7 (for group 2), on day 12 (for group 1, 3) as primary end points and 28 days after post therapy as secondary end point. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Azithromycin showed significant improvement radiographically on day 7 (P < 0.01) and on day 35 (P < 0.01). Gatifloxacin elicited very highly significant improvement radiographically on day 40 (P < 0.001) and significant improvement on day 12 (P < 0.01) when compared with amoxicillin. Azithromycin, the ketolide was associated with lesser adverse effects as compared to amoxicillin. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Gatifloxacin was found to be most effective drug both in terms of improvement in signs and symptoms on visual analogue scale and radiographic scoring and was associated with least adverse events in comparison to rest of two drugs under study.     

Radiation therapy versus surgery for patients with cervical squamous cell carcinoma who have undergone neoadjuvant chemotherapy revisited

Background

The therapeutic significance of neoadjuvant chemotherapy (NAC) followed by radiation therapy (RT) was negated during the early 1990s. Here, we compared post-NAC RT to surgery for chemo-sensitive cervical squamous cell carcinoma (SCC).

Methods

This study included 79 consecutive patients with cervical SCC who were treated by NAC followed by surgery (n = 49) or by definitive RT (n = 30). We compared characteristics and survival outcomes between the surgery and RT groups by their responses to NAC.

Results

Of the 79 patients, 70 (89%) had stage II–IV disease and 41 (52%) had radiological pelvic lymph node enlargement. The 5-year disease-specific survival (DSS) rate of the entire cohort was 66.4% (median follow-up 54 months). Fifty-five patients (70%) achieved sufficient (complete or partial) responses to NAC. Among patients with insufficient NAC responses, the 5-year DSS rate of the surgery group (55.6%) was significantly higher than the RT group (20.0%; P = 0.044). However, among patients with sufficient responses to NAC, 5-year DSS rates did not significantly differ between the surgery and RT groups (82.3 vs 78.6%; P = 0.79) even though the RT group had many more unfavorable prognostic factors and received fewer subsequent treatments than the surgery group.

Conclusions

Post-NAC survival outcomes among patients with chemo-sensitive cervical SCC who then underwent RT were not inferior to those treated with surgery, and NAC did not detract from the efficacy of subsequent RT. Among selected patients who respond favorably to NAC, RT could be a less invasive substitute for surgery without compromising treatment outcomes.

     

The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients

Background

The preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic marker for gastric cancer patients. However, the utility of the NLR in predicting short-term outcomes in gastric cancer patients remains unclear. Here, we investigated whether the preoperative NLR is a predictor of short-term outcomes in gastric cancer patients.

Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear Implantation

To test whether there are variations in cochlear orientation with respect to age and sex, and its relevance in cochlear implant surgery. Implant otologists rely upon the anatomic landmarks including the facial recess and round window niche and round window membrane for accessibility and placement of electrode array into scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in cochlear orientation with respect to age. Cochlear orientation studied radiologically by pre-operative CT scan of temporal bone can guide a Surgeon’s approach to cochlear implantation. To investigate the changes in cochlear orientation with respect to age and sex; and its relevance in cochlear implantation. A retrospective analytical study was performed on CT scans of temporal bones in patients (of our hospital from July 2013 to January 2015 i.e. for a period of 18 months) with no congenital or radiological abnormalities of cochlea. The basal turn angulations of cochlea varied with age and majority of change occurred during early age. The basal turn angulations of cochlea in difficult situations during cochlear implantation were correlated with the data. There is a significant variation in cochlear orientation as measured radiologically by basal turn angulations relative to midsagittal plane. The more obtuse and acute basal turn angulations have implications like difficulty in cochleostomy and electrode placement during cochlear implantation.     

Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy

Purpose

Our sincere hope is to establish the predictive factors of neoadjuvant chemotherapy (NAC) response and provide patients with greater certainty regarding treatment outcomes. The aim of this study was to assess the response to NAC and survival in patients with locally advanced rectal cancer (LARC) according to their RAS/BRAF mutation status.

Methods

Data on 57 patients with LARC who received NAC between 2009 and 2016 were analyzed retrospectively. The patients were classified into two groups based on their mutation status: wild-type in both RAS and BRAF (WT) or mutant-type in either RAS or BRAF (MT).

Results

Twenty-three patients were classified as WT, and the remaining 34 patients were MT. Histological response to NAC was similar in both groups. In responders, the 3-year relapse-free survival (RFS) was better compared with the non-responders (92 and 66%, respectively). In the WT group, the 3-year RFS was 95% which was significantly better than that in the MT group (59%, p = 0.011). The MT group was further subdivided into the following 2 groups by the pathological response; the MT responders (n = 10) and MT non-responders (n = 24). The 3-year RFS was 50% in the MT non-responders, which was significantly worse compared to that in the remaining patients (92%, p = 0.001).

Conclusion

RAS/BRAF mutations did not affect the response to NAC. However, the RFS was likely to be poor for those in the MT group who did not achieve favorable pathological response. In contrast, the RFS was favorable in the WT group regardless of the pathological response.

     

Comparison of laparoscopic proximal gastrectomy with double-tract reconstruction and laparoscopic total gastrectomy in terms of nutritional status or quality of life in early gastric cancer patients

Background

This study aimed to evaluate the surgical outcomes of laparoscopic proximal gastrectomy (LPG) reconstructed by the double-tract method in comparison to those of laparoscopic total gastrectomy (LTG).

Role of Transient Evoked Otoacoustic Emission Beyond Screening of Hearing Impairment: A Study of 400 Cases

The primary purpose of this study was to investigate the potential role of transient-evoked Otoacoustic emissions (TEOAEs) beyond screening for hearing impairment in different middle/inner ear disorders in 3–65 years age group. Because TEOAEs are present in ears with normal cochlear and middle ear function and typically are absent or reduced in ears with cochlear and/or middle ear disorders of even mild degree. This was a prospective study of four hundred cases. Out of these 364 cases were having problems related to otology and 36 were healthy volunteers who attended the department of otorhinolaryngology of our institute. All the cases were kept in different eight groups and then subjected to Otoacoustic emission testing with the ‘GSI AUDIO screener’ equipment installed in our ENT department. The data obtained in all groups were analyzed and conclusion was made. TEOAEs is a reliable, simple and cost effective screening technique for hearing disorders with sensitivity varying from 72 to 96.42 % among the study groups and 88 % in composite group comprising all study groups.