Efficacy of Vitamin D Supplementation in Allergic Rhinitis

Allergic Rhinitis is one of the most commonly recognised rhinitis globally. Though its not a life threatening entity but it is associated with severe impairment of quality of life along with substantial financial burden on patient. There has been a substantial rise in number of patients of allergic rhinitis over years and researchers worldwide have also found low levels of vitamin D in patients of allergic rhinitis. It is a randomised control trial with 87 subjects divided into two groups. Pre-treatment total nasal symptom score (TNSS) were recorded for these patients. The Group A was given intranasal steroidal spray while Group B was given vitamin D supplementation along with intranasal steroidal spray. Post treatment TNSS scores and rhinitis control assessment test scores were calculated and analysed. 38 patients had severe Vit D deficiency with average TNSS score as 11.3 while 49 patients had insufficient Vit D levels with average TNSS as 8.6. The pre-treatment TNSS score in Group A was 12.5 ± 2.68 while post-treatment score was 8.98 ± 1.009 with difference in both scores of Group A as 3.52. The pre-treatment TNSS score in Group B (fluticasone spay with Vit D) was 11.64 ± 3.09 while post-treatment score was 6.3 ± 1.45 with difference in both scores of Group A as 5.34. The post treatment RCAT in Group A and Group B was 19.72 ± 2.84 and 28.2 ± 1.53 respectively with difference between two groups as 8.48. Though Intranasal steroidal sprays are the first line of management of allergic rhinitis however vitamin D supplementation can have a role in better relief of symptoms when used in conjunction. More multi-institutional studies are encouraged to confirm the validity of results before it can be incorporated in standard treatment guidelines.     

Extrinsic intestinal denervation modulates tumor development in the small intestine of ApcMin/+ mice

Background

Innervation interacts with enteric immune responses. Chronic intestinal inflammation is associated with increased risk of colorectal cancer. We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model.

Methods

Experiments were performed with male Apc^Min/+ or wild type mice (4 weeks old, body weight approximately 20 g). Subgroups with subdiaphragmatic vagotomy (apcV/wtV), sympathetic denervation of the small intestine (apcS/wtS) or sham operated controls (apcC/wtC) were investigated (n = 6-14 per group). Three months after surgical manipulation, 10 cm of terminal ileum were excised, fixed for 48 h in 4% paraformaldehyde and all tumors were counted and their area determined in mm² (mean ± standard error of the mean (SEM)). Whole mounts of the muscularis of terminal ileum and duodenum (internal positive control) were also stained for tyrosine hydroxylase to confirm successful sympathetic denervation.

Results

Tumor count in Apc^Min/+ mice was 62 ± 8 (apcC), 46 ± 11 (apcV) and 54 ± 8 (apcS) which was increased compared to wildtype controls with 4 ± 0.5 (wtC), 5 ± 0.5 (wtV) and 5 ± 0.6 (wtS; all p < 0.05). For Apc^Min/+ groups, vagotomized animals showed a trend towards decreased tumor counts compared to sham operated Apc^Min/+ controls while sympathetic denervation was similar to sham Apc^Min/+. Area covered by tumors in Apc^Min/+ mice was 55 ± 10 (apcC), 31 ± 8 (apcV) and 42 ± 8 (apcS) mm², which was generally increased compared to wildtype controls with 7 ± 0.6 (wtC), 7 ± 0.4 (wtV) and 7 ± 0.6 (wtS) mm² (all p < 0.05). In Apc^Min/+ groups, tumor area was decreased in vagotomized animals compared to sham operated controls (p < 0.05) while sympathetically denervated mice showed a minor trend to decreased tumor area compared to controls.

Conclusions

Extrinsic innervation of the small bowel is likely to modulate tumor development in Apc^Min/+ mice. Interrupted vagal innervation, but not sympathetic denervation, seems to inhibit tumor growth.     

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

Background

Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model.

Materials and methods

HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured.Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination.

Results

The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively.

Conclusions

The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model.     

Treatment and outcomes of patients with light chain amyloidosis who received a second line of therapy post autologous stem cell transplantation

We retrospectively reviewed 292 patients who received a second line of therapy post ASCT for their light chain amyloidosis. Most patients (40%) were treated with an alkylator + PI ± dex or PI ± dex followed by an alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex (26%), an alkylator ± steroid or steroid monotherapy (19%), a 2nd-gen IMiD + PI ± dex (6%), an alkylator + thalidomide ± dex (5%), or daratumumab-based therapy (4%). The rate of CR or VGPR was 70% among the daratumumab-based group, 62% in the alkylator + PI ± dex or PI ± dex group, 55% in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 47% in the 2nd-gen IMiD + PI ± dex group, 24% in the alkylator ± steroid or steroid monotherapy group, and 18% in the alkylator + thalidomide ± dex group. The median OS was NR for the 2nd-gen IMiD + PI ± dex group and the daratumumab group, 130.4 months in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 100 months for the alkylator + PI ± dex or PI ± dex group, 36 months for the alkylator ± steroid or steroid monotherapy group, and 21 months for the alkylator + thalidomide ± dex group (P < 0.0001). The median OS was 100 months in patients who received melphalan 200 mg/m² compared to 41 months in the 140 mg/m² group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m² at diagnosis had better outcomes.Subject terms: Haematological diseases, Medical research     

Ultrasound features of medullary thyroid carcinoma correlate with cancer aggressiveness: a retrospective multicenter study

Background

Poor prognosis of medullary thyroid cancer (MTC) with suspicious ultrasound (US) features has been reported. The aim of the study was to investigate the association between preoperative US presentation and aggressiveness features of MTC. Also, US features of MTC were compared with those previously reported.

Methods

Study group comprised 134 MTC from nine different centers. Based on US presentation the nodules were stratified in “at risk for malignancy” (m-MTC) or “probably benign” (b-MTC) lesions.

Results

Eighty nine (66.4%) m-MTC and 45 (33.6%) b-MTC were found. Metastatic lymph nodes (p = 0.0001) and extrathyroid invasiveness (p < 0.0001) were more frequent in m-MTC. There was statistically significant correlation (p = 0.0002) between advanced TNM stage and m-MTC with an Odds Ratio 5.5 (95% CI 2.1–14.4). Mean postsurgical calcitonin values were 224 ± 64 pg/ml in m-MTC and 51 ± 21 in b-MTC (p = 0.003).

Conclusions

This study showed that sonographically suspicious MTC is frequently associated with features of aggressiveness, suggesting that careful preoperative US of MTC patients may better plan their surgical approach.     

Vitamin D3 enhances the tumouricidal effects of 5-Fluorouracil through multipathway mechanisms in azoxymethane rat model of colon cancer

Background

Vitamin D3 and its analogues have recently been shown to enhance the anti-tumour effects of 5- Fluorouracil (5-FU) both in vitro and in xenograft mouse model of colon cancer. This study measured the potential mechanism(s) by which vitamin D3 could synergise the tumouricidal activities of 5-FU in azoxymethane (AOM) rat model of colon cancer.

Methods

Seventy-five male Wistar rats were divided equally into 5 groups: Control, AOM, AOM-treated by 5-FU (5-FU), AOM-treated by vitamin D3 (VitD3), and AOM-treated by 5-FU + vitamin D3 (5-FU/D). The study duration was 15 weeks. AOM was injected subcutaneously for 2 weeks (15 mg/kg/week). 5-FU was injected intraperitoneally in the 9th and 10th weeks post AOM (8 total injections were given: 12 mg/kg/day for 4 successive days, then 6 mg/kg every other day for another 4 doses) and oral vitamin D3 (500 IU/rat/day; 3 days/week) was given from week 7 post AOM till the last week of the study. The colons were collected following euthanasia for gross and histopathological examination. The expression of β-catenin, transforming growth factor-β1 (TGF-β1), TGF-β type 2 receptor (TGF-βR2), smad4, inducible nitric oxide synthase (iNOS), and heat shock protein-90 (HSP-90) proteins was measured by immunohistochemistry. In colonic tissue homogenates, quantitative RT-PCR was used to measure the mRNA expression of Wnt, β-catenin, Dickkopf-1 (DKK-1) and cyclooxygenase-2 (COX-2) genes, while ELISA was used to measure the concentrations of TGF-β1, HSP-90 and COX-2 proteins.

Results

Monotherapy with 5-FU or vitamin D3 significantly decreased the number of grown tumours induced by AOM (P < 0.05); however, their combination resulted in more significant tumouricidal effects (P < 0.05) compared with monotherapy groups. Mechanistically, vitamin D3/5-FU co-therapy significantly decreased the expression of Wnt, β-catenin, iNOS, COX-2 and HSP-90 and significantly increased the expression of DKK-1, TGF-β1, TGF-βR2, smad4 (P < 0.05), in comparison with their corresponding monotherapy groups.

Conclusions

Vitamin D3 and 5-FU synergise together and exhibit better anticancer effects by modulating Wnt/β-catenin pathway, TGF-β1 signals, iNOS, COX-2 and HSP-90. Further studies are required to illustrate the clinical value of vitamin D supplementation during the treatment of colon cancer with 5-FU in human patients.     

Anatomical and Surgical Study to Evaluate the Accuracy of “C-M-S” Technique in Facial Nerve Identification During Parotid Surgery

Facial nerve identification is considered to be a crucial step in parotid surgery as inadvertent injury to the nerve will lead to facial paralysis. Multiple landmarks are described in literature to identify the facial nerve during parotid surgery but controversies remain as the consistency and accuracy of these landmarks vary. Numerous studies exist in literature but they fail to address a single landmark that is most reliable to identify the facial nerve during parotid surgery. The purpose of this study is to find reliable landmarks for identification of the main trunk of facial nerve during parotid surgery by evidence gathered by cadaveric dissection and intraoperative study during parotid surgery and develop a systematic approach to identify the facial nerve trunk. This prospective study included 41 cadavers (82 parotid regions) and 20 patients with parotid pathology who underwent parotidectomy. We evaluated the feasibility of our C-M-S technique to identify the main trunk of facial nerve in both anatomical and surgical study. The relationship of landmarks (tragal pointer, tympanomastoid suture, superior border of posterior belly of digastric muscle) to the facial nerve trunk was assessed and the shortest distance between them from the facial trunk was measured using a slide caliper. The measurements were compared between the anatomical and surgical study. The main trunk of facial nerve was successfully identified in all cases using C-M-S technique in both anatomical and surgical study. Distance of facial nerve trunk to tragal pointer was more in the cadaveric sample (13.04 ± 5.238 mm) compared to live patients (9.95 ± 3.967 mm) with statistically significant difference (p = 0.036). The mean distance of tympanomastoid suture and posterior belly of digastric muscle to the facial nerve trunk was similar in anatomical and surgical study with p value of 0.877 and 0.083 respectively. The tympanomastoid suture, posterior belly of digastric muscle and tragal pointer are the most useful landmarks for facial nerve identification during parotid surgery. In our study we found that the tympanomastoid suture line is the most consistent landmark present in all our cases and being closest to the facial nerve trunk in both anatomical and surgical study. Further we recommend using the “C-M-S technique” in order to locate the main trunk of the facial nerve.     

New Visionary in Upper Airway Surgeries–THRIVE,a Tubeless Ventilation

THRIVE stands for Transnasal Humidified Rapid Insufflation Ventilatory Exchange. Usage of THRIVE technique is common in emergency settings and of late its usage in upper airway surgeries is gaining popularity. (1) To determine the operative time, total anaesthesia time, safety and efficacy of THRIVE in patients undergoing upper airway surgeries for varied pathologies. (2) To assess the surgeon’s satisfaction and patients post-operative comfort. An observational study was from May 2019 to Oct 2020. Study was conducted through a detailed proforma which consists of patient demographic details, physical status, co-morbidities and various domains to assess the safety and efficacy of THRIVE. A total of 32 patients were divided into four groups depending on the type of surgery. We had 18 patients in microlaryngeal excision, six in direct laryngoscopy and biopsy, four in tracheostomy and four in balloon dilatation for subglottic stenosis groups. The mean operation time was 16 ± 2 min in the first three groups and 29 ± 0.8 in the fourth group. All the patients underwent successful surgeries without any episodes of desaturation, without complications and with good surgical satisfaction. THRIVE with appropriate safety precautions can be tried in patients undergoing various upper airway surgeries of short duration. All the patients in our study maintained stable vital parameters throughout the surgery. Initial results with the use of THRIVE as per our study and other studies are definitely encouraging to use THRIVE in upper airway surgeries with varied pathologies.     

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer

Background:

Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC.

Methods:

Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS).

Results:

The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 μg ml⁻¹ and 69.8±14.3 μg ml⁻¹; in plasma were 1.87±0.4 μg ml⁻¹ and 0.055±0.009 μg ml⁻¹. The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 μg g⁻¹ and 30.1±18.3 μg⁻¹g⁻¹, respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3–4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications.

Conclusions:

HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.     

Endonasal Endoscopic Approach in Management of Paediatric CSF Rhinorrhoea Cases

Though endoscopic repair has been the proven to be the gold standard for the repair of cerebrospinal fluid rhinorrhoea in adult patients, the type of approach to be used in paediatric patients especially those below 5 years is still a challenge with no clear cut guidelines. The objective of this study was to evaluate the efficacy of using endonasal endoscopic approach for treating paediatric patients aged less than 5 years diagnosed with cerebrospinal fluid rhinorrhoea. This was a retrospective analysis of five cases of paediatric CSF rhinorrhoea operated in a tertiary health care centre with an age of less than 5 years from October 2002 to September 2010. All the five cases treated by endoscopic approach have no further complaints of CSF leak or meningitis with a follow up period of a minimum period of 6 months. Two cases were further detected to have meningocele and meningoencephalocele which was detected preoperatively and treated by reduction and excision respectively. The good results obtained by endoscopic closure with lack of major complications and the decreased morbidity for the patient suggests that the endoscopic approach should be considered the first line of approach in pediatric population. But we would warrant a careful selection procedure and availability of adequate expertise for this approach to avoid complications.     

Assessment of Site,Degree and Pattern of Airway Obstruction in Patients with Moderate to Severe Obstructive Sleep Apnoea (OSA) Using Drug Induced Sleep Endoscopy (DISE)and Its Association with Awake Fibreoptic Evaluation and Polysomnography Parameters

Accurate assessment of site of obstruction in Obstructive Sleep Apnoea (OSA) is key to its effective management, especially the surgical intervention. Currently, Drug induced sleep endoscopy (DISE) is widely used to assess the obstruction during sleep as assessing during physiologic sleep is impractical and cumbersome. To assess the site, pattern and degree of airway obstruction in patients with moderate to severe obstructive sleep apnoea using DISE and to find a co-relation of DISE findings with awake fibreoptic assessment and severity of OSA. 41 adult patients (29 males, 12 females, mean AHI 40.58 ± 16.94, mean age 54 ± 9.15 years underwent awake fibreoptic nasal endoscopy in the outpatient department and propofol induced DISE in the main operation theatre. The site/s, degree and pattern of obstruction were recorded as per VOTE and Fujita classification. Velum was the commonest site of collapse followed by oropharynx, base of tongue and epiglottis. All had multilevel collapse with velum, oropharynx and base of tongue being the most common combination. At velum, base of tongue and epiglottis, antero-posterior pattern of collapse was commonest and at oropharynx lateral pattern of collapse was the commonest. We found no difference in the site, pattern or severity of collapse between the moderate and severe group though there was a tendency of epiglottis collapse being present more frequently in severe OSA. Awake fibreoptic endoscopic evaluation was able to assess the collapse at level of velum with higher sensitivity but with poor specificity. There was high chances of missing a hypopharyngeal collapse with fibreoptic endoscopic evaluation.Keyword: Obstructive sleep apnoea, Drug induced sleep endoscopy, VOTE classification, Level of collapse, Awake FONPL, Fujita classification     

Treatments after progression to first-line FOLFOXIRI and bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies by GONO

Background FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression.Methods We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction.Results Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045).Conclusions First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.Subject terms: Colorectal cancer, Chemotherapy     

To evaluate the role of Feracrylum (1%) as hemostatic agent in Tonsillectomy

Tonsillectomy is a common procedure performed globally. It is associated with morbidities like hemorrhage and pain. Various methods are employed to reduce them. The present study is aimed to evaluate the role of Feracrylum (1%) in traditional cold steel tonsillectomy and to measure the outcomes in terms of intra-operative bleed, intra-operative time and post operative pain and recovery. A prospective study was conducted in Department of ENT, ESI Medical College, Kalburgi Karnataka, India, for a period of two years between January 2019 to December 2020 In this study, a total of 60 patients were involved and divided them into two groups after fulfilling the inclusion and exclusion criteria. Thirty patients each undergoing tonsillectomy with the use of Feracrylum considered as Group I and without the use of Feracrylum in the tonsillar fossae considered as Group II. The study has been approved by Ethics committee and informed consent was obtained from all the study subjects. The amount of blood loss is calculated. Post operative pain based on VAS (Visual Analogue Scale) is assessed in both the groups. Assessment of recovery in days is estimated in both groups by reduced pain, gaining normal activity and normal food intake. In this study, intra-operative time in group I was 19.83 ± 3.93 min and in group II 27.16 ± 3.35 min (P < 0.001). The intra-operative blood loss in group I was 26.67 ± 4.81 ml and in group II 44.70 ± 7.59 ml (P < 0.001). Patients recovered from pain, resumed normal activity and food intake within 2–3 days in Group I and in contrast it took about 3–5 days on an average in group II. In this study, majority of the patients experienced mild pain in Group I when Feracrylum was used during hemostasis. In our study, the time taken by the patients to recover from pain, resume their normal activity and also with regard to normal food intake was rapid. On an average of 2–3 days was seen in Group I. Group II patients required 3–5 days to recover from pain and resuming normal activity and food intake. The P value of < 0.001 was highly significant. Our study has stressed that use of Feracrylum in cold steel tonsillectomy is relatively safe. Its use is associated with a significant decrease in surgical time and blood loss. Rapid recovery makes it favourable to be used in cold steel tonsillectomy.     

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

Background Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours.Methods We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. The starting doses were berzosertib 18 mg/m², gemcitabine 875 mg/m² and cisplatin 60 mg/m².Results Fifty-two patients received berzosertib + gemcitabine and eight received berzosertib + gemcitabine + cisplatin. Four patients receiving berzosertib + gemcitabine had a total of seven dose-limiting toxicities (DLTs) and three receiving berzosertib + gemcitabine + cisplatin had a total of three DLTs. Berzosertib 210 mg/m² (days 2 and 9) + gemcitabine 1000 mg/m² (days 1 and 8) Q3W was established as the recommended Phase 2 dose (RP2D); no RP2D was determined for berzosertib + gemcitabine + cisplatin. Neither gemcitabine nor cisplatin affected berzosertib PK. Most patients in both arms achieved a best response of either partial response or stable disease.Conclusions Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.Clinical trial identifier {"type":"clinical-trial","attrs":{"text":"NCT02157792","term_id":"NCT02157792"}}NCT02157792.Subject terms: Medical research, Cancer     

Endoscopic Septoplasty: A Retrospective Analysis of 415 Cases

Nasal obstruction is the most common complaint in nasal and sinus disease. Deviated nasal septum is a very frequently encountered and common cause. Surgical correction of a deviated septum- nasal septoplasty- is the definite treatment for septal deviation. Over the last 2 decades, the applications for endoscopy in the field of rhinology have evolved beyond functional endoscopic sinus surgery (FESS). Septoplasty which is among the three most commonly performed procedures in otolaryngology is particularly well suited to endoscopic application. Endoscopic septoplasty as a minimally invasive technique can limit the dissection and minimize trauma to the nasal septal flap under excellent visualization whose primary advantage is to decrease morbidity and post operative swelling in isolated septal deviation by limiting the excision to the area of deviation. This was a retrospective study, conducted in a tertiary care medical college hospital over a period of 5 years. The study group comprised 415 patients in and around Nashik District; who visited our tertiary health centre and were subjected to endoscopic septoplasty. Complete data records from 415 patients were available for statistical analysis. Maximum numbers of patients were in age group 20–39. The youngest patient was 7 years old and oldest was 75 years. Mean age was 32 years. The 7 years old was operated for DCR for congenital NLD block and septoplasty was adjunct procedure. Even the 75 years was operated for DCR. In the present study out of 415 cases, 256 (67.5 %) cases were male and 115 (32.5 %) cases were female. There is a male preponderance in the overall distribution of cases. In the present study of 415 patients, the most common operative procedure done was septoplasty in 260 (62.6 %), FESS with septoplasty in 38 (9.2 %) cases, septorhinopolasty in 41 (9.9 %) cases and DCR with septoplasty in 78 (18.3 %) cases. Endoscopic septoplasty facilitates good access to accomplish endoscopic DCR, FESS, and accurate and adequate septal graft harvest in severely deviated noses for septorhinoplasty. Complications like dental pain, paraestaesia, septal perforation, saddle nose deformity and persistent deviation are a rarity.     

Endothelial follicle-stimulating hormone receptor expression in invasive breast cancer and vascular remodeling at tumor periphery

Background

Follicle-stimulating hormone receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.

Methods

We used immunohistochemical techniques involving specific antibodies to detect FSHR and the endothelial markers (CD34, VEGFR2, and D2-40) in tissue samples from 83 patients with lymph node-negative, invasive breast cancer representing four main clinical treatment groups: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative.

Results

The FSHR+ vessels were exclusively located at breast cancer periphery, in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm², respectively). These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors. The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups. FSHR+ vessels did not express VEGFR2. The endothelial FSHR expression correlated significantly with the peritumoral CD34+ vessels’ density (p < 0.001) and tumor size (p = 0.01).

Conclusion

Endothelial FSHR expression in breast cancer is associated with vascular remodeling at tumor periphery.     

Faecal immunochemical test for patients with ‘high-risk’ bowel symptoms: a large prospective cohort study and updated literature review

Background We evaluated whether faecal immunochemical testing (FIT) can rule out colorectal cancer (CRC) among patients presenting with ‘high-risk’ symptoms requiring definitive investigation.Methods Three thousand five hundred and ninety-six symptomatic patients referred to the standard urgent CRC pathway were recruited in a multi-centre observational study. They completed FIT in addition to standard investigations. CRC miss rate (percentage of CRC cases with low quantitative faecal haemoglobin [f-Hb] measurement) and specificity (percentage of patients without cancer with low f-Hb) were calculated. We also provided an updated literature review.Results Ninety patients had CRC. At f-Hb < 10 µg/g, the miss rate was 16.7% (specificity 80.1%). At f-Hb < 4 µg/g, the miss rate was 12.2% (specificity 73%), which became 3.3% if low FIT plus the absence of anaemia and abdominal pain were considered (specificity 51%). Within meta-analyses of 9 UK studies, the pooled miss rate was 7.2% (specificity 74%) for f-Hb < 4 µg/g.Discussion FIT alone as a triage tool would miss an estimated 1 in 8 cases in our study (1 in 14 from meta-analysis), while many people without CRC could avoid investigations. FIT can focus secondary care diagnostic capacity on patients most at risk of CRC, but more work on safety netting is required before incorporating FIT triage into the urgent diagnostic pathway.Subject terms: Colorectal cancer, Diagnostic markers     

Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases

Cytogenetic studies among 809 consecutive patients with essential thrombocythemia (ET; median age 59 years; 65% females) revealed normal karyotype in 754 (93%), loss of chromosome Y only (-Y) in 16 (2%), and abnormalities other than -Y in 39 (4.8%), the most frequent being sole 20q- (n = 8). At presentation, abnormal karyotype, excluding -Y, was associated with older age (p = 0.04), higher leukocyte count (p = 0.03) and arterial thrombosis history (p = 0.02); no associations were apparent for JAK2/CALR/MPL mutations whereas ASXL1 mutations clustered with normal karyotype/-Y and TP53 with abnormal karyotype. Survival was significantly shorter in patients with abnormal karyotype or -Y, compared to those with normal karyotype (median 12, 10, and 21 years, respectively; p < 0.0001). During multivariable analysis that included IPSET (international prognostic score for ET) variables, abnormal karyotype (p < 0.01, HR 2.0), age >60 years (p < 0.01, HR 4.5), leukocytosis >11 × 10⁹/L (p < 0.01, HR 1.5), and male gender (p < 0.01, HR 1.4) were independently associated with inferior survival; abnormal karyotype and age >60 years remained significant, along with SF3B1/SRSF2/U2AF1/TP53 mutations (p = 0.04; HR 2.9), when the latter was included in the multivariable model. The current study suggests prognostic relevance for karyotype in ET.Subject terms: Myeloproliferative disease, Myeloproliferative disease     

CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma

Background

Invasive ductal carcinoma is the most common type of breast malignancy, with varying molecular features and resistance to treatment. Although CD44+/CD24- cells are believed to act as breast cancer stem cells and to be linked to poor prognosis in some patients, the association between these cells and tumor recurrence or metastasis in all or some types of invasive ductal carcinoma is unclear.

Methods

A total of 147 randomly selected primary and secondary invasive ductal carcinoma samples were assayed for expression of CD44, CD24, ER, PR, and Her2. The association between the proportions of CD44+/CD24- tumor cells and the clinico-pathological features of these patients was evaluated.

Results

CD44+/CD24- tumor cells were detected in 70.1% of the tumors, with a median proportion of 5.8%. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement (P = 0.026) and PR status (P = 0.038), and was correlated with strong PR status in patients with recurrent or metastatic tumors (P = 0.046) and with basal-like features (p = 0.05). The median disease-free survival (DFS) of patients with and without CD44⁺/CD24^-/low tumor cells were 22.9 ± 2.2 months and 35.9 ± 3.8 months, and the median overall survival (OS) of patients with and without CD44⁺/CD24^-/low tumor cells were 39.3 ± 2.6 months and 54.0 ± 3.5 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44⁺/CD24^-/low tumor cells was strongly correlated with DFS and OS.

Conclusion

The prevalence of CD44+/CD24- tumor cells varied greatly in invasive ductal carcinomas, with the occurrence of this phenotype high in primary tumors with high PR status and in secondary tumors. Moreover, this phenotype was significantly associated with shorter cumulative DFS and OS. Thus, the CD44⁺/CD24^- phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.     

Hyaluronan in the Treatment of Chronic Rhinosinusitis with Nasal Polyposis

Chronic rhinosinusitis (CRS) is a common condition and affects the quality of life of approximately 16 % of adults in US and 10.9 % in Europe. Hyaluronan (HA) is a nonsulphate glycosaminoglycan found in the extracellular matrix of connective tissues, and plays an important role in the healing process and repair of mucosal surfaces. We aim to evaluate the effect of HA on nasal symptoms and endoscopic appearance in patients with CRS and nasal polyps (NP) who have not undergone sinus surgery. Eighty patients older than 18 years old were randomized to receive either open-label nebulized saline solution (NS) or intranasal corticosteroid spray (ICS) 200 µg bid or nebulized sodium hyaluronate (NHA, YABRO^®) or both ICS and NHA. Results were collected at 1 month, 3 months and 3 months after treatment. Significant improvements in nasal symptoms scores, endoscopic appearance scores, radiologic scores, rhinomanometry and saccharine clearance test were observed in the NHA, ICS and ICS + NHA groups after 1 month and 3 months of treatment compared with baseline (all p ≤ 0.005). The use of oral steroids was significantly reduced after 3 months of therapy in the same groups versus baseline (all p < 0.05). The incidence of adverse events at 3 months was similar between the 4 groups (all p > 0.05). Throat irritation, nasal burning and drug-related epistaxis were not reported in the group NHA. HA, as a nebulized nasal douche preparation, improved nasal symptoms and endoscopic appearances in patients with CRS and NP who have not undergone sinus surgery.