Stage I Breast Cancer in the Modern Era: A Retrospective Cohort Study of 328 Patients Diagnosed from 2002 to 2006 with a 14- year Median Follow-Up.

INTRODUCTION: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. METHODS: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS). The influence of tumor size, grade, and subtype on the outcomes was analyzed. RESULTS: Most patients were treated by lumpectomy, sentinel node biopsy and adjuvant endocrine therapy and most (82%) were of subtype luminal-A. Adjuvant chemotherapy was administered to 25.6 % of our cohort. Only 24 patients underwent gene expression testing, which was introduced toward the end of the study period. Mean IDFS was 14.64 years, with a 15-year IDFS of 75.6%. Mean OS was 15.28 years with a 15-year OS of 74.9%. In a Cox multivariate analysis, no clinical or pathologic variable impacted on OS and only tumor size (< 1 centimeter (cm) vs 1-2 cm), impacted significantly on IDFS. During follow-up, 20.1% of the cohort developed second primary cancers, including BC. The median time to diagnosis of a second BC was 6.49 years. CONCLUSION: The study results emphasize the importance of long-term follow-up and screening for subsequent malignancies of patients with stage I BC and support the need for using prognostic and predictive indicators beyond the routine clinicopathological characteristics in luminal-A patients.

Diagnosis of Sarcopenic Dysphagia in the Elderly: Critical Review and Future Perspectives.

Sarcopenic dysphagia (SD) is swallowing difficulty associated with loss of generalized skeletal muscles and swallowing-related muscles. Diagnostic criteria for SD were suggested, yet there is a variability in instruments and cut-offs used. The aim of the current review is to critically evaluate tools used in diagnosis of sarcopenic dysphagia in the elderly. Comprehensive review of the literature was performed. Studies were qualitatively evaluated for the diagnostic tools used to make a diagnosis of "sarcopenic dysphagia" and compared to the known diagnostic criteria for SD and other accepted measures. Fourteen studies (N = 10,282) were selected from a search yield of 331 de-duplicated studies. Ninety-three percent of studies (13/14) were conducted in Japan. All subjects included were over the age of 65 years old (mean, 76.5 years). Various tools were used to assess sarcopenia including handgrip strength (14/14 of studies), followed by skeletal muscle mass/index (7/14), tongue pressure, gait speed, and calf circumference in 5/14 studies. The most commonly tool used for dysphagia and/or swallowing dysfunction was the food level intake scale (5/14 of studies) followed by the functional oral intake scale (3/14). The 100-mL water swallow test was used in 2 of the 14 included SD studies. Fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, EAT-10 questionnaire, and standardized swallow assessment were each used in only one SD study. Further research is required to validate SD diagnostic tools, establish cut-offs in different populations, and investigate their role in screening of dysphagia and swallowing dysfunction in the elderly.

Outcomes in modified transoral resection of diverticula for Zenker's diverticulum.

PURPOSE: Transoral resection of Zenker's diverticulum (TORD) was first reported in 2010. We present results for our modified approach to transoral resection (MTORD)-full-thickness cricopharyngeal myectomy, diverticulum sac excision, and suture closure of the pharyngotomy-and evaluate its safety and efficacy compared to endoscopic stapling and open approaches. METHODS: A retrospective study was performed in patients who underwent transoral resection of Zenker's diverticulum using MTORD, endoscopic stapler-assisted diverticulotomy (ESD), or trancervical diverticulectomy (TCD) from July 2009 to August 2017. Pre-operative evaluation included barium swallow and subjective characterization of swallowing dysfunction using the EAT-10 and Reflux Symptom Index (RSI). Complications, length of hospitalization, recurrence, and revision rates were also evaluated. RESULTS: Of 92 patients reviewed, 18 underwent MTORD, 45 underwent ESD and 29 underwent TCD. Major complications were only observed in ESD and TCD. Recurrence which required revision surgery was only observed in ESD. EAT-10 and RSI scores significantly improved and RSI scores normalized post-operatively for all approaches in short-term (< 1 year) follow-up. CONCLUSIONS: MTORD is a safe and effective option for complete Zenker's diverticulectomy. Complication rates are low. To date, no patient has required reoperation, although more cases and longer term follow-up are needed for more complete comparison to ESD and traditional open excision.

Long-term health-related quality of life after mandibular resection and reconstruction.

PURPOSE: To compare short- and long-term quality of life (QOL) scores in patients undergoing mandibular resection and reconstruction. MATERIALS AND METHODS: All the patients who underwent resection and reconstruction of the mandible between 2000 and 2015 at a large tertiary center were retrospectively reviewed. Their QOL was measured by the University of Washington QOL questionnaire. Between 12 and 189 months (median 83.5 months) had elapsed since the end of treatment. The QOL of the short-term (< 5 years) and long-term (> 5 years) follow-up groups was compared and analyzed. RESULTS: Fifty-eight patients completed the questionnaire. The scores for physical function, emotional function, activity, recreation, and taste domains were significantly higher for the long-term follow-up group. The activity and pain domains posed a significant problem for significantly more patients in the short-term follow-up group. CONCLUSION: Comparison of the short- and long-term QOL scores of patients undergoing mandibular resection and reconstruction revealed that the scores for the latter were significantly higher in several domains. This finding might be indicative of a cumulative effect of time on patients' QOL, even many years post-treatment.

The incidence of malignancy in clinically benign cystic lesions of the lateral neck: our experience and proposed diagnostic algorithm.

AIM: Solitary cystic masses of the lateral neck in an adult patient can pose a diagnostic dilemma. Malignancy must be ruled out since metastases arising from H&N cancers may mimic the presentation of benign cystic masses. Only a small number of studies have investigated the diagnostic management and malignancy rate of clinically benign solitary cervical cystic lesions. There are no established guidelines for the diagnostic evaluation. METHODS: Retrospective review of the clinical, cytological, radiological, and pathological records of all adult patients (> 18 years) operated on for second branchial cleft cysts (BrCC) between 1/2008-2010/2016. Patients with apparent primary H&N malignancy, history of H&N cancer or irradiation, preoperative fine needle aspiration (FNA) of highly suggestive or confirmed malignancy, missing pertinent data, or age less than 18 years were excluded from analysis. RESULTS: 28 patients were diagnosed as having BrCC. The diagnosis was based on clinical findings, FNA cytology, and typical sonographic features. The histologic analysis determined an overall rate of malignancy of 10.7% (3/28): two patients had metastatic papillary thyroid carcinoma, and one patient had metastatic tonsillar squamous cell carcinoma. Purely cystic features on pre-operative ultrasound was the only significant predictor for true BrCC on final histology (p = .02). CONCLUSIONS: Occult malignancy is not rare among adult patients presenting with a solitary cystic mass of the lateral neck. A diagnostic algorithm is proposed. Further studies are needed to establish the appropriate workup and management of an adult patient presenting with a solitary cystic mass of the lateral neck.

The clinical behavior of sinonasal inverted papilloma with cellular dysplasia: case series and review of the literature.

The prognosis and recurrence rate of inverted papilloma (IP) with concomitant cellular dysplasia are not well-delineated. Demographic, clinical and imaging data of all patients who were surgically treated for sinonasal inverted papilloma (SNIP) in our center between 1996 and 2013 were reviewed. Data regarding the coexistence of dysplastic changes or malignancy within the resected tissues were also retrieved. After the exclusion of malignant cases and patients who were lost for follow-up, 92 patients were included in the study. Five patients had coexisting cellular dysplasia (4.7%), four of them had severe dysplasia and one had mild-to-moderate dysplasia. All four cases with severe dysplasia recurred, three were primarily treated endoscopically and one by external approach. Only the case with mild to moderate dysplasia which had been treated by subcranial approach did not recur. Patients with dysplasia had significantly higher recurrence rate than patients without dysplasia (80 vs. 14%, p = 0.019). This significant relation between histology and recurrence remained even after adjustment to tumor extent. The adjusted odd ratio of dysplasia (dysplasia vs. no dysplasia) is 9.7, p = 0.043. SNIP with dysplasia should be treated aggressively and followed closely. The histopathologic investigation of SNIP specimens should always note the presence of dysplasia and its severity. Further investigation on the clinical behavior of SNIP with dysplasia is needed. Multicenter studies are warranted due to the rarity of dysplastic SNIP.

Histopathologic classification of parapharyngeal space tumors: a case series and review of the literature.

The objective of the study is to present a large case series of parapharyngeal space tumors (PPST) and the most comprehensive literature review of tumor histopathologic distribution. The study was designed as internal case series and full Pubmed/MEDLINE electronic database review in a tertiary academic medical center. Tumor histopathology and patient demographics were obtained from a comprehensive Pubmed/MEDLINE database review, as well from an internal case series of 117 patients referred to our center between 1993 and 2013. Main outcome and measures of the study were to define the age, gender, and histopathology of PPST within a large internal case series and among the current body of published literature, and to propose a diagnostic and treatment algorithm for these tumors. Our cohort included 117 cases, 58 females and 59 males, with benign tumors comprising 85 % (n = 99) and malignant tumors 15 % (n = 18). A systematic review of published literature from 1963 to the present revealed 37 case series, and when combined with our present series, yielded a total of 2160 cases. Benign tumors are most common (78.8 %), with tumors of salivary gland (44.4 %), neural (34.4 %), and vascular (2.64 %) origin representing the largest subtypes. Pleomorphic adenomas (30.9 %), paragangliomas (13.1 %), and schwannomas (12.3 %) comprised the majority of all cases. Due to their rarity, data regarding the histopathologic distribution of PPST is scarce. We provide one of the largest case series and the most comprehensive review of these tumors in the literature to date, and offer our algorithm for evaluation and treatment.

Smartphone-based audiometric test for screening hearing loss in the elderly.

Hearing loss is widespread among the elderly. One of the main obstacles to rehabilitation is identifying individuals with potentially correctable hearing loss. Smartphone-based hearing tests can be administered at home, thus greatly facilitating access to screening. This study evaluates the use of a smartphone application as a screening tool for hearing loss in individuals aged ≥ 65 years. Twenty-six subjects aged 84.4 ± 6.73 years (mean ± SD) were recruited. Pure-tone audiometry was administered by both a smartphone application (uHear for iPhone, v1.0 Unitron, Canada) and a standard portable audiometer by trained personnel. Participants also completed a questionnaire on their hearing. Pure-tone thresholds were compared between the two testing modalities and correlated with the questionnaire results. The cutoff point for failing screening tests was a pure tone average of 40 dB for the frequencies 250-6,000 Hz. The smartphone application's pure tone thresholds were higher (poorer hearing) than the audiometric thresholds, with a significant difference in all frequencies but 2,000 Hz. The application and the audiometric values were in agreement for 24 subjects (92 %). The application had a sensitivity of 100 % and specificity of 60 % for screening compared with the audiometer. The questionnaire was significantly less accurate, having assigned a passing score to three participants who failed both the application and audiometric tests. While a smartphone application may not be able to accurately determine the level of hearing impairment, it is useful as a highly accessible portable audiometer substitute for screening for hearing loss in elderly populations.

One stage combined endoscopic and per-oral buccal fat pad approach for large oro-antral-fistula closure with secondary chronic maxillary sinusitis.

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF ≤ 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9 %), foreign body in sinus (n = 10, 22.2 %) nasal congestion (n = 7, 15.5 %), halitosis (n = 6, 13.3 %) and pain (n = 5, 12.2 %). Surgical complications included local pain (n = 2, 4.4 %), persistent rhinitis (n = 2, 4.4 %) and synechia (n = 1, 2.2 %). One patient required revision surgery due to an unresolved OAF. The OAF of all the other 44 patients (97.8 %) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

Validation of the Hebrew Version of the Eating Assessment Tool-10 (H-EAT-10).

BACKGROUND AND OBJECTIVES: Dysphagia is a common disability with different etiologies. In order to measure dysphagia symptom severity and effects on quality of life, the Eating Assessment Tool (EAT-10) was developed and validated in the English language. We aimed to develop a Hebrew version of the EAT-10 and to evaluate its internal consistency, test-retest reliability, and validity in Hebrew-speaking adults with dysphagia. SUBJECTS AND METHODS: The Hebrew EAT-10 (H-EAT-10) questionnaire was completed by 132 patients: 56 patients with dysphagia and 76 controls. Internal consistency analysis was calculated using Cronbach α, and test-retest reliability was calculated using intraclass correlation coefficient in order to assess clinical validity. RESULTS: Internal consistency and test-retest reliability were found to be high in the H-EAT-10 (Cronbach α = 0.955 and intraclass correla tion = 0.98). In addition, H-EAT-10 scores in the dysphagia group were found to be significantly higher than those in the control group (p < 0.001). CONCLUSION: This study demonstrated that H-EAT-10 is a reliable and valid tool that may be implemented for clinical practice and research on dysphagia in a Hebrew-speaking population.

Combined maxillary sinus floor elevation and endonasal endoscopic sinus surgery for coexisting inflammatory sinonasal pathologies: a one-stage double-team procedure.

OBJECTIVES: To report our experience with combined one-stage double-team maxillary sinus floor elevation (SFE) and endonasal endoscopic sinus surgery (ESS) procedure for concomitant inflammatory sinonasal pathologies. MATERIAL AND METHODS: Clinical records of all patients that underwent maxillary SFE in conjunction with endonasal ESS for the treatment of inflammatory sinonasal pathologies between 2011 and 2013 were retrospectively reviewed. All included patients had a sinonasal-related pathology that was first suggested by the referring physician and was later confirmed clinically and radiographically by our combined team comprised of otorhinolaryngologist and maxillofacial surgeons. RESULTS: Fifteen combined SFE+ESS surgeries were performed using either xenograft-allograft mixture or autograft-xenograft-allograft mixture. The study group included seven males and eight females, whose median age was 55 years (range, 45-78 years). Seven patients underwent a unilateral SFE, and eight patients underwent bilateral SFEs. During the same session, four patients also underwent septoplasty for deviated nasal septum, five patients underwent bilateral maxillary antrostomy, 10 patients underwent unilateral maxillary antrostomy, and six patients underwent maxillary sinus cyst resection. Seven combined procedures were performed under active infection. There were no intra-operative complications, and all SFE+ESS combined procedures were successful. Three patients required extended postoperative antibiotic treatment for persistent sinusitis. One patient reported infraorbital hypoesthesia. CONCLUSIONS: We first report the promising outcomes of the double-team one-stage SFE+ESS procedure performed by a combined team of otorhinolaryngologist and maxillofacial surgeons, including on patients presenting with an infection of the sinuses at the time of surgery.

Nasopharyngeal biopsy in adults: a large-scale study in a non endemic area.

BACKGROUND: Limited data exist on the referral criteria for endoscopic-guided nasopharyngeal biopsy to rule out nasopharyngeal malignancy among adults in a non-endemic area. METHODS: Retrospective study of all adult patients that had been referred to our outpatient clinic to undergo endoscopic-guided nasopharyngeal biopsy to exclude nasopharyngeal malignancy between 1/2006-10/2013. All medical consultation referral letters were reviewed, and statistical analyses were conducted to evaluate clinically significant predictors (demographics, clinical manife- stations, nasopharyngeal endoscopic findings) for nasopharyngeal malignancy. RESULTS: A total of 470 patients (470 nasopharyngeal biopsies, 54.9% males and 66% smokers) were included. The most common pathological result was adenoid/lymphoid hyperplasia (76.2%). The overall negative rate of all biopsies for malignancy was 94.2%. Twenty-seven patients had nasopharyngeal malignancy: 22 had squamous cell carcinoma and 5 had non-Hodgkin`s lymphoma. Advanced age, cervical mass, and suspicious nasopharyngeal mass were independent risk factors for nasopharyngeal malignancy on univariate and multivariate analyses. CONCLUSIONS: Nasopharyngeal biopsy may safely be avoided in adults living in a non-endemic area for NPC who are free of the risk factors of advanced age, the presence of a cervical mass, and suspicious nasopharyngeal mass.

Outcomes of endonasal endoscopic dacryocystorhinostomy after maxillectomy in patients with paranasal sinus and skull base tumors.

Maxillectomy followed by radiotherapy and/or chemotherapy can result in lacrimal blockage and the need for subsequent dacryocystorhinostomy (DCR). Endonasal endoscopic DCR, as opposed to external DCR, allows better accuracy and leaves no scar. To date no report was published regarding the results of endoscopic DCR in these patients. The current study presents a retrospective review of all patients with paranasal and skull base tumors who developed nasolacrimal duct blockage after ablative maxillectomy with or without radiotherapy and/or chemotherapy and underwent endonasal endoscopic DCR between January 2006 and October 2012 in a tertiary reference medical center. According to our results, ten patients underwent 11 subsequent endonasal endoscopic DCR. There were 6 men and 4 women with a median age of 55 years (range, 19-81 years); four suffered from benign tumors and six had malignant tumors. All underwent maxillectomy. Six received high-dose radiotherapy. Time interval between primary ablative surgery and endonasal endoscopic DCR was 18 months (range, 7-118 months). Silicone stents were removed after median period of 11 weeks (range, 1-57 weeks). Nine out of ten patients experienced symptomatic improvement following one endonasal endoscopic DCR. One patient had recurrent epiphora and underwent a successful endonasal endoscopic revision DCR. In conclusion, endonasal endoscopic DCR in patients with paranasal and skull base tumors, who previously underwent maxillectomy, is generally successful and not associated with a high rate of complications or failure. Moreover, our findings may suggest that silicone stents can be removed shortly after the operation with high success rate.

Assessment of Swallowing Function in Healthy Adults While Using High-Flow Nasal Cannula.

OBJECTIVE: Despite widespread use of high flow nasal cannula (HFNC) for respiratory support, the effect of HFNC on swallowing physiology is poorly understood. Flow rates that permit safe swallowing have not been established. We aim to assess if healthy individuals have diminished swallowing function and safety at high flow rates. STUDY DESIGN: Repeated measures with planned data collection. SETTING: Outpatient dysphagia clinic. METHODS: Swallowing function in a cohort of healthy individuals was assessed using Flexible Endoscopic Evaluation of Swallowing (FEES). Participants' safety of swallowing was assessed with different textures under randomized rates of HFNC (0, 30, 40, 50, and 60 LPM). Swallowing trials included quantities of thin liquids, mildly-thick liquids, and purees. Trials were scored using the Penetration-Aspiration Scale (PAS). Pearson chi-square tests were used to test for correlation between PAS result, flow rate, and consistency across each quantity of material. RESULTS: Twenty-seven subjects were enrolled. Forty-one percent were male with mean age of 34 years (11 standard deviation). Ninety-nine percent (267/270), 97% (n = 263/270), and 99% (399/405) of 1 sip swallows, 3 sip swallows, and 5 mL swallows, respectively, were safe. There was no significant correlation between swallow safety and flow rate using Pearson Chi-Square test across all consistencies and across all quantities of materials (P > 0.05). Of note, out of all subtrials, the thin liquid, 3 sips trial at 60 LPM, had the largest percent of unsafe swallows (14%). CONCLUSION: Our results suggest rate of aspiration is not significantly affected by high flow nasal cannula in healthy individuals.

Validation of a 3D-Printed Percutaneous Injection Laryngoplasty Simulator: A Randomized Controlled Trial.

OBJECTIVE: Simulation may be a valuable tool in training laryngology office procedures on unsedated patients. However, no studies have examined whether existing awake procedure simulators improve trainee performance in laryngology. Our objective was to evaluate the transfer validity of a previously published 3D-printed laryngeal simulator in improving percutaneous injection laryngoplasty (PIL) competency compared with conventional educational materials with a single-blinded randomized controlled trial. METHODS: Otolaryngology residents with fewer than 10 PIL procedures in their case logs were recruited. A pretraining survey was administered to participants to evaluate baseline procedure-specific knowledge and confidence. The participants underwent block randomization by postgraduate year to receive conventional educational materials either with or without additional training with a 3D-printed laryngeal simulator. Participants performed PIL on an anatomically distinct laryngeal model via trans-thyrohyoid and trans-cricothyroid approaches. Endoscopic and external performance recordings were de-identified and evaluated by two blinded laryngologists using an objective structured assessment of technical skill scale and PIL-specific checklist. RESULTS: Twenty residents completed testing. Baseline characteristics demonstrate no significant differences in confidence level or PIL experience between groups. Senior residents receiving simulator training had significantly better respect for tissue during the trans-thyrohyoid approach compared with control (p < 0.0005). There were no significant differences in performance for junior residents. CONCLUSIONS: In this first transfer validity study of a simulator for office awake procedure in laryngology, we found that a previously described low-cost, high-fidelity 3D-printed PIL simulator improved performance of PIL amongst senior otolaryngology residents, suggesting this accessible model may be a valuable educational adjunct for advanced trainees to practice PIL. LEVEL OF EVIDENCE: NA Laryngoscope, 134:318-323, 2024.

[Metastatic spinal cord compression: diagnosis and treatment].

Metastatic epidural spinal cord compression is a common complication of cancer that can cause pain and potentiaLly irreversible loss of neurologic function. In most cases this syndrome is caused by compression of the thecal sac and the spinal cord by extradural metastatic mass. The most important steps in minimizing the potential neurologic sequelae are early diagnosis and rapid therapeutic intervention. MRI is generally the preferred imaging modality because of its noninvasive ability to study the entire thecal sac. Surgery and radiotherapy are the primary approaches to treat tumor compressing the spinal cord.

The Use of Oxygen/Air Blender during Transoral Laser Microsurgery with Supraglottic Manual Jet Ventilation: A Safe Approach.

Background: Surgical fires are known, preventable, and devastating complications of transoral microlaryngeal laser surgery. Several guidelines have recommended maintaining the fraction of inspired oxygen concentration (FiO2) at or below 30% for open delivery cases. We hereby present our experience utilizing an air/oxygen gas mixing device (blender) attached to a supraglottic manual jet ventilator during transoral laser microlaryngeal surgery in three cases to control oxygen levels. Methods: Retrospective chart review of three cases and literature review. Results: Three patients underwent microlaryngeal laser surgery and balloon dilation for the management of subglottic stenosis. All three patients were successfully ventilated throughout the procedures, and no major complications occurred intraoperatively. Two of three patients demonstrated symptomatic and clinical improvement at the first follow-up. Conclusions: This report demonstrates the successful use of an oxygen/air blender to reduce FiO2 to fire-safe levels of less than 30% during laser surgery of the airway using jet ventilation.

Laryngeal Trauma.

Laryngeal trauma is rare but potentially fatal. Initial evaluation includes efficient history and physical examination, imaging, bedside flexible laryngoscopy, and if necessary, operative endoscopic evaluation. Multiple classification systems exist for laryngeal trauma, and each has its merits. We recommend a patient-centered approach, rather than using the classification alone. Secure airways are the primary goal of acute management, with awake tracheostomy more often indicated over oral intubation compared with traumas not involving the larynx. More severe injuries typically require surgical intervention. Early intervention results in optimal voice and airway outcomes.

Localization of PKCη in cell membranes as a predictor for breast cancer response to treatment.

BACKGROUND: Successful treatment of breast cancer is frequently limited by the resistance of tumors to chemotherapy. Recent studies suggested a role for protein kinase C (PKC) in the resistance to chemotherapy. Here we used retrospective analysis of breast cancer biopsies of neoadjuvantly treated patients to investigate the correlation of PKC expression with aggressiveness and resistance to chemotherapy. PATIENTS AND METHODS: Our cohort (n = 25) included patients with advanced and aggressive breast cancers, who underwent neoadjuvant therapy with the CAF regimen (cyclophosphamide, doxorubicin, fluorouracil). Core biopsies (pre-chemotherapy) and surgical biopsies of primary tumors and lymph node metastases (post-chemotherapy) were scored for PKCeta (PKCh) and PKCepsilon (PKCe) expression in the cytoplasm, cell membrane, nuclear membrane, and the nucleus. RESULTS: Our results showed increased expression of PKCh (not PKCe) in the cytoplasm and cell membranes of post-chemotherapy biopsies (p = 0.03). PKCh presence in cell membranes, indicating activation, was in correlation with poor survival (p = 0.007). CONCLUSION: PKCh staining in cell and nuclear membranes is an indicator for poor survival and a predictor for the effectiveness of neoadjuvant treatment. Other avenues of treatment should be considered for these patients. PKCh presents a target for therapy where inhibition of its activity and/or translocation to membranes could interfere with the resistance to chemotherapy.

Lack of prenatal care in a traditional community: trends and perinatal outcomes.

PURPOSE: To describe the prevalence of lack of prenatal care (LOPC) over the years and to examine the association between LOPC and perinatal complications among Bedouin parturients. METHODS: A retrospective study comparing all singleton births of Bedouin women with and without prenatal care, between the years 1988 and 2009, was conducted. Multiple logistic regression models were used to control for confounders. RESULTS: Out of 123,506 singleton deliveries, 16.5% (n = 20,402) were of women lacking prenatal care. A gradual increase in the rate of LOPC was noted between the years 2006 and 2009. Using multivariable analyses, controlling for parity, LOPC was found to be significantly associated with preterm delivery (PTD) < 37 weeks (odds ratio (OR) 1.13, 95% CI 1.07-1.19), PTD < 34 weeks (OR 1.53, 95% CI 1.40-1.67), low birth weight < 2,500 g (LBW; OR 1.39, 95% CI 1.32-1.46), very LBW < 1,500 g (OR 1.67, 95% CI 1.49-1.86), and perinatal mortality (OR 1.63, 95% CI 1.47-1.80). CONCLUSIONS: Lack of prenatal care in a traditional community is associated with adverse obstetric outcomes and specifically is an independent risk factor for preterm delivery, low birth weight, and perinatal mortality.