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Pathogen emergence (PE) is a complex phenomenon with major public health implications. Over the past decades, numerous underlying mechanisms facilitating the emergence of pathogenic bacteria have been elucidated. In this review, we highlight the diverse molecular and environmental drivers associated with PE, with an emphasis on the interplay of canonical gene transfer mechanisms and the increasingly appreciated role of genetic variations, providing a more coherent picture of this process. Given the interactive and multifactorial nature of PE, we contend that the development of approaches that embrace the integration of these factors is indispensable in order to truly comprehend this complex phenomenon and develop strategies to mitigate this threat.

Pathogen emergence is a poorly understood complex phenomenon. To date, the molecular mechanisms that allow strains within a bacterial population to emerge as human pathogens remain mostly enigmatic. We recently uncovered that toxigenicVibrio choleraeencode preadaptations to host colonization, what we term virulence adaptive polymorphisms (VAPs), however, the molecular mechanisms driving them are not known.ompUis a VAP-encoding gene that is associated with the production of the major outer membrane porin OmpU. Here, we show that theompUORF also encodes a modular small RNA overlapping its 3’ terminus that plays a major role inV. choleraephysiology. We determined that the OmpU-encoded sRNA (OueS) strongly suppresses biofilm formation, a phenotype that is essential for host intestinal colonization, via repression of iron uptake. OueS controls over 84% of the genes regulated by ToxR, a major virulence regulator, and plays an integral role during the infection process. We demonstrate that OueS is critical for intestinal colonization and its bimodular nature dictates the virulence potential ofV. cholerae. Overall, our study reveals specific molecular mechanisms leading to the emergence of pathogenic traits in bacteria unveiling the hidden genetics associated with this process. We propose a scenario where a limited number of modular genes could explain the emergence of novel phenotypic traits in biological systems.

Due to the risk of occult cervical metastasis, elective neck dissection (END) is recommended in the management of patients with early oral cavity squamous cell carcinoma (OSCC) and a clinically node-negative (cN0) neck. This paper presents a systematic review and meta-analysis of studies that recorded isolated regional recurrence (RR) in the pathologically node-negative neck dissection (pN0) neck following END in order to quantify the failure rate. Pubmed and Ovid databases were systematically searched for relevant articles published between January 2009 and January 2019. Studies reporting RR following END in patients with OSCC who had no pathological evidence of lymph node metastasis were eligible for inclusion in this meta-analysis. In addition, a selection of large head and neck units were invited to submit unpublished data. Search criteria produced a list of 5448 papers, of which 18 studies met the inclusion criteria. Three institutions contributed unpublished data. This included a total of 4824 patients with median follow-up of 34 months (2.8 years). Eight datasets included patients staged T1-T4 with RR 17.3% (469/2711), 13 datasets included patients staged T1-T2 with RR 7.5% (158/2113). Overall across all 21 studies, isolated neck recurrence was identified in 627 cases giving a RR of 13.0% (627/4824) on meta-analysis. Understanding the therapeutic effectiveness of END provides context for evaluation of clinical management of the cN0 in these patients. A pathologically negative neck does not guarantee against future recurrence.

The evaluation of speech outcomes after resection and reconstruction of the oral tongue remains largely unsystematic. A cross-sectional study was performed to analyse the speech outcomes of patients who underwent curative treatment with appropriate reconstruction. Sixty-nine patients were assessed for speech intelligibility and phonetics using a validated speech intelligibility assessment tool in the local language. Volume defects were classified as class I (less than one third), II (one third to half), III (half to two-thirds), or IV (two-thirds to total glossectomy). Defect location was defined as lateral, tip, or sulcus. The χ2 test and Kruskal-Wallis test were used to test volume and location as predictors. Twenty-six patients had class I defects, 29 had class II defects, seven had class III defects, and seven had class IV defects. Twenty-two patients (31.9%) received adjuvant radiotherapy. Mean vowel, consonant, word, and paragraph intelligibility were 99.27%, 86.86%, 85.52%, and 88.72%, respectively. The incremental volume of the glossectomy defect was significantly correlated with speech intelligibility scores and phonatory alterations. In classes II and III, tip resection significantly affected interdental sounds. All patients in class III had affected alveolar and alveo-palatal sounds. The results positively corroborated the volume and location of the glossectomy defect to a classification system.

Background Nomograms applying the 8th edition of the TNM staging system aimed at predicting overall (OS), disease-specific (DSS), locoregional recurrence-free (LRRFS) and distant recurrence-free survivals (DRFS) for oral tongue squamous cell carcinoma (OTSCC) are still lacking. Methods A training cohort of 438 patients with OTSCC was retrospectively enrolled from a single institution. An external validation set of 287 patients was retrieved from two independent institutions. Results Internal validation of the multivariable models for OS, DSS, DRFS and LRRFS showed a good calibration and discrimination results with optimism-corrected c-indices of 0.74, 0.75, 0.77 and 0.70, respectively. The external validation confirmed the good performance of OS, DSS and DRFS models (c-index 0.73 and 0.77, and 0.73, respectively) and a fair performance of the LRRFS model (c-index 0.58). Conclusions The nomograms herein presented can be implemented as useful tools for prediction of OS, DSS, DRFS and LRRFS in OTSCC.

This study aimed to characterize the swallowing outcomes after glossectomy and analyze factors affecting them. An attempt is made to propose a classification system and corroborate it to the results. This is a cross-sectional study to assess swallowing in carcinoma tongue patients treated surgically with or without reconstruction, followed by adjuvant therapy as indicated. One hundred and six patients were evaluated with videofluoroscopy (VFS). Volume defects were classified as I: less than one-third, II: one-third to half, III: half to two-thirds, IV: two-thirds to total glossectomy. Location was assigned as lateral, tip, and sulcus defects. Predictors were T stage, surgical approach, volume, location, and adjuvant radiotherapy. Chi-square and logistic regression were used for statistical analysis. Defects were Class I, II, III, and IV in 36, 42, 16, and 12 patients, respectively. Adjuvant radiotherapy was given in 40% of cases. Mean evaluation time was 14 months from treatment. On, Functional Oral Intake Scale (FOIS) score, as the Class of the defect increased, the percentage of patients with low scores (poor swallowing outcomes) showed an increasing trend (p

The aim of this study was to identify patterns of tumor growth as revealed on magnetic resonance imaging (MRI) and to evaluate the correlation of these patterns with histopathologic features and rates of recurrence, disease-free survival (DFS), and overall survival (OS).In a retrospective analysis of patients with tongue carcinoma, tumor advancing margins, patterns of tumor enhancement, and enhancement beyond tumor margins were studied on MRI. Histopathologic findings included differentiation, margin status, perineural invasion (PNI), and lymphovascular invasion (LVI). MRI and histopathologic features were correlated with outcomes.Ill-defined tumor margins and enhancement beyond tumor margins were associated with recurrences (P ≤ .001) regardless of perineural invasion or LVI. DFS and OS were adversely affected by ill-defined tumor margins (P ≤ .010). DFS was also affected by enhancement beyond the tumor margins (P.001). A heterogeneous pattern of enhancement showed a trend toward a decrease in DFS and OS (P = .088 and .092, respectively). Advancing tumor margins on MRI were independent predictors of overall survival. MRI characteristics exhibited significant associations with histopathologic margins, PNI, and LVI.Ill-defined advancing tumor margins, a heterogeneous pattern of enhancement, and enhancement beyond the tumor margins on MRI adversely affect outcomes and prognosis in tongue carcinoma.

Background The purpose of the study was to evaluate the oncological outcomes of salvage surgery in squamous cell carcinoma of the head and neck (SCCHN). Methods This is a retrospective analysis of all patients of SCCHN with recurrence or second primary, post-treatment, who underwent salvage surgery. The outcomes were analyzed in terms of overall survival, overall survival postsalvage surgery and disease-free survival (DFS) postsalvage surgery. Clinical and pathological predictors were considered. Results Two hundred and forty-one patients were included. The mean follow-up was 56.33 months. Five-year survival OS from date of initial diagnosis of the tumor was 61.2%. The 5-year OS survival after salvage surgery was 47.1%. Five-year DFS after salvage surgery was 28.1%. Prior chemoradiotherapy and pathological perineural invasion were independent predictors on multivariate analysis. Conclusions Survival outcomes after appropriate salvage treatment are good. Prior chemoradiotherapy and perineural invasion on salvage pathology are predictors of poorer outcomes.

Vibrio cholerae O1, a natural inhabitant of estuarine environments, is found in a dormant, viable but non-culturable (VBNC) state during interepidemic periods. Although the individual roles of abiotic factors affecting VBNC formation have been extensively studied, their interplay in driving this phenomenon remains largely unaddressed. Here, we identified that major abiotic factors synergize with low nutrient conditions governing entry of cells into the VBNC state. Specifically, V. cholerae cells exposed to a combination of alkaline pH and high salinity under aeration at low temperatures (VBNC-inducing conditions) synergize to facilitate rapid entry into VBNC, whereas the opposite conditions prevented entry into the state. The major virulence regulator ToxR, and the stringent response protein RelA played opposing roles, repressing and facilitating VBNC entry respectively. Further, VBNC-inducing conditions negated the effects of ToxR and RelA, facilitating rapid formation of VBNC cells. In summary, this study highlights the synergy between critical abiotic factors and identified ToxR and RelA as two associated regulators, allowing for the persistence of V. cholerae in aquatic environments. Insights obtained in this study will help better understand environmental survival non-sporulating bacteria and transmission of facultative bacterial pathogens.

ObjectivesPharyngocutaneous fistulae are dreaded complications following total laryngectomy. This paper presents our experience using 3–5 ml gastrografin to detect pharyngeal leaks following total laryngectomy, and compares post-operative videofluoroscopy with clinical follow-up findings in the detection of pharyngocutaneous fistulae.MethodsA retrospective case–control study was conducted of total laryngectomy patients. The control group (n = 85) was assessed clinically for development of pharyngocutaneous fistulae, while the study group (n = 52) underwent small-volume (3–5 ml) post-operative gastrografin videofluoroscopy.ResultsIn the control group, 24 of 85 patients (28 per cent) developed pharyngocutaneous fistulae, with 6 requiring surgical correction. In the study group, 24 of 52 patients (46 per cent) had videofluoroscopy-detected pharyngeal leaks; 4 patients (8 per cent) developed pharyngocutaneous fistulae, but all cases resolved following non-surgical management. Patients who underwent videofluoroscopy had a significantly lower risk of developing pharyngocutaneous fistulae; sensitivity and specificity in the detection of pharyngocutaneous fistulae were 58 per cent and 100 per cent respectively.ConclusionSmall-volume gastrografin videofluoroscopy reliably identified small pharyngeal leaks. Routine use in total laryngectomy combined with withholding feeds in cases of early leaks may prevent the development of pharyngocutaneous fistulae.

Oral tongue carcinomas represent more than half of the tumors arising in the oral cavity, a site with a high cancer specific mortality and impact on quality of life. Current guidelines are lacking for a standardized surgical approach of these tumors. The aim of this study is to compare two currently adopted surgical strategies, compartmental surgery (CTS) and wide local excision (WLE), with loco-regional control as the main oncological endpoint.An observational retrospective multicentric study was carried out enrolling a cohort of patients affected by oral tongue or floor of the mouth squamous cell carcinoma and surgically treated in 4 international tertiary referral centers. Survival analysis was performed by propensity-score matching approach and multivariable Cox regression analysis.A cohort of 933 patients was enrolled. CTS was applied in 113 patients (12.1%) and WLE in 820 (87.9%). Analyzing a propensity-score matched cohort (98 CTS vs. 172 WLE) and applying a survival multivariable modeling strategy on the whole cohort, both confirmed that CTS and WLE are comparable and oncologically safe. Parameters such as number of positive lymph nodes, depth of invasion, and lymphovascular invasion still represent the key prognosticators.The main goals for surgical resection of oral cancer remain its three-dimensional circumferential clearance with adequate margins and en-bloc removal of the tumor-lymph node tract, independently of the technique adopted (CTS or WLE). Further prospective studies including quality of life evaluation are needed to better understand if one of these approaches can provide superior functional outcomes.

Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well-established features like perineural invasion (PNI), differentiation, and lymphovascular-invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3-4).Seven hundred and forty-two patients with T3-4 OSCC underwent surgery from 2006 to 2013. Cox regression was performed to determine predictors of overall survival (OS).OS was adversely impacted by PNI (p = 0.046), LVI (p = 0.038), moderate/poor differentiation (p = 0.001), close/involved surgical margins (p = 0.002), pT (p = 0.034), and pN (p 0.001). The cumulative number of adverse histopathological features predicted poorer OS; HR 2.64 (CI 1.42-4.90) for one adverse feature and HR 4.23 (CI 2.34-7.67) for ≥2.In advanced OSCC, stratification with histopathologic risk factors can predict survival even in maximally treated patients; adjuvant therapies are unable to entirely mitigate this risk. Incorporation of adverse features into future editions of TNM can improve precision in staging and identify candidates for treatment escalation.

Vibrio cholerae O1 is the aetiological agent of the severe diarrhoeal disease cholera. Annually, there are an estimated 1–4 million cholera cases worldwide and over 140 000 deaths. The primary mode of disease transmission is through the consumption of water or food contaminated with the bacterium. Although cholera patients can be treated effectively using rehydration therapy, the disease remains a major scourge in areas with limited access to clean water and proper sanitation. Its continued prevalence highlights the failure of socioeconomic policies leading to wealth disparities, fragile and dated public infrastructure, and lack of appropriate health surveillance.

Background: Microvascular flap reconstruction (MFR) of medium–large tongue defects following ablative surgery is the standard of care. The decision for MFR is often made prior to surgery or intraoperatively depending on the extent of the defect and the volume of remnant tongue. However, there exists no objective technique to predict this requirement preoperatively. This knowledge is crucial for counseling and planning. We aimed to identify an objective magnetic resonance imaging (MRI) measurement tool to predict the need for MFR of tongue tumors. Materials and Methods: This was a retrospective analysis of patients undergoing surgery (with or without reconstruction) for squamous cell carcinoma of the tongue. Patients had a preoperative MRI as part of their assessment. As per our institution protocol, the decision for the requirement of MFR was made by a consensus of two experienced reconstructive surgeons intraoperatively. This decision was correlated with the ratio of tumor volume to the total tongue volume (tv) as observed in the MRI. Results: A total of 47 patients were identified. Twenty-eight patients underwent reconstruction, while 19 did not. The ratio of tumor thickness to tongue thickness (Tt/tt) was calculated, and a cutoff of >0.395 (sensitivity 89.3% and specificity 89.5%) was found to significantly correlate with the decision for MFR (P < 0.001). The volume of a tumor to total tv ratio was calculated from the data of 22 cases, and a cutoff of >4.2 (sensitivity 83.3 and specificity 90) was found to be correlated significantly with the decision for MFR (P < 0.001). Conclusion: Tt/tt ratio is a useful tool to determine the need for MFR of tongue tumor excision defects in the preoperative setting and can help guide counseling.

Radial forearm free flap (RAFF) is the workhorse flap for oral cavity reconstruction. In the context of oncological reconstruction with radial forearm flap, the patient-reported outcomes of donor site morbidity amongst Indian patients have not been reported previously. Cultural and racial differences prevent extrapolation of morbidity data from Western literature. We aimed to evaluate subjectively the subjective long-term functional and aesthetic outcomes of the RAFF donor site. Patients who underwent RAFF reconstruction for intra-oral defects between 2014 and 2016 were included. Two questionnaires (Cosmesis and Sensibility and Forearm Disability) were administered. Fifty-two patients who completed a 2-year follow-up were identified. Thirty-five patients (67%) had complaints regarding the donor site. With regard to cosmesis and sensibility, hand numbness was seen in 21 (40.4%) patients. With regard to forearm disability, a problem in lifting heavy weights was seen in 22 (42.3%) patients. Only three patients in the entire cohort had complaints regarding the cosmesis of the forearm scar. Overall disability score was low (7.83). With regard to donor site morbidity, numbness and difficulty in lifting weights was the most common complaint. There is good acceptance of the donor site and scar with minimum morbidity. These findings are useful for the preoperative counselling of the patients. This is the first Indian study evaluating the long-term subjective outcomes of the radial forearm donor site. We believe the RAFF is still the most preferred flap for oral reconstruction.

Objectives To study the determinants of locoregional control (LRC) on stage I/II oral squamous cell carcinoma (OSCC) classified by AJCC 8th edition. Methods Retrospective analysis from 296 patients of pT1-2N0 oral OSCC treated with surgery (wide local excision and selective neck dissection). Those receiving adjuvant therapy were excluded. Multivariate analysis was performed for impact of adverse pathological features (APFs) on LRC. Results In stage I, LRC was impacted by perineural invasion (PNI) (HR 7.72, p = 0.010, 95% CI 1.64–36.26) and moderate/poor differentiation (MD/PD) (HR 3.04, p = 0.049, 95% CI 0.99–9.25). In stage II, LRC was impacted by depth of invasion (DOI) (HR 1.59, p = 0.014, 95% CI 1.099–2.32), PNI (HR = 2.86, p = 0.005, 95% CI 1.36–5.98). Combined MD/PD and PNI were associated with worse LRC than either feature individually (HR = 4.12, p Conclusion PNI and differentiation accurately predict LRC in AJCC 8th edition classified stage I/II OSCC. PNI was a stronger predictor of locoregional failure than DOI in stage II disease. By incorporating these parameters, we can improve precision in staging of early OSCC and identify potential candidates for treatment escalation to improve outcomes.

Purpose of review Marginal mandibular nerve palsy (MMNP) is often an understated complication after neck dissection. This article reviews literature regarding anatomic landmarks that help define marginal mandibular nerve (MMN) during neck dissection, oncologic safety of surgical maneuvers, implications of MMNP, and reconstructive options. Recent findings A thorough knowledge of anatomy of the nerve can aid in its preservation. Course, branching pattern and communications of MMN are extremely variable. The Hayes Martin method classically described to preserve the nerve may not be oncologically safe in patients with prefacial nodal involvement. MMNP significantly affects quality of life after neck dissection. Cause, timing, and degree of neural damage play an important role in determining diagnostic and therapeutic options to correct the deformity resulting from MMNP. Owing to treatment-related factors, functionality of local structures may be compromised, which limits available reconstructive options for the surgeon. This should favor a shift of management option toward more conservative procedures in patients treated for head and neck cancer. Summary When oncologically safe, the MMN must always be preserved. The patient perceived deformity resulting from MMNP is significantly higher than clinician-detected rate. In select patients who are affected by significant smile asymmetry, multiple dynamic and static corrective procedures can be offered.

According to the eighth edition of the AJCC Cancer Staging Manual (AJCC8), a depth of invasion (DOI)10mm is classified as pT3, representing a locally advanced tumour requiring postoperative radiotherapy (PORT). When node-negative, however, evidence regarding whether PORT improves loco-regional control or survival is unclear. To clarify this, two cohorts of patients were studied: (1) patients classified as pT3N0 by the seventh edition of the AJCC manual (AJCC7), with DOI10mm and a tumour diameter4cm (17 patients who received PORT), and (2) patients classified as pT1N0 and pT2N0 by AJCC7, with DOI10mm and a tumour diameter4cm (55 patients who did not receive PORT). Loco-regional control and survival were analysed. PORT was found not to impact overall survival or disease-free survival. It was also found not to impact local, regional, or distant recurrence. Although the two subsets of patients considered here (DOI10mm with tumour diameter below or above 4cm) were previously distinct, they are both considered pT3 in AJCC8. Data from this study indicate that the routine administration of PORT to patients with a DOI10mm may not be warranted in the absence of other risk features such as nodal disease or close margins.

Osteoradionecrosis (ORN) is a painful and debilitating serious late complication following treatment for head and neck cancer (HNC) often requiring surgical resection of the jaw and complex multidisciplinary management. An important aggravating factor for mandibular ORN is surgical trauma, commonly dental extractions or implant placement following head and neck radiotherapy. The evidence on the treatment protocols ranges from conservative management to more radical surgical strategies including the use of hyperbaric oxygen therapy. The available evidence on the preventive approaches for ORN includes prophylactic dental care prior to radiotherapy, the use of hyperbaric oxygen (HBO) treatment and prophylactic antibiotics for post-radiotherapy extractions. However, the efficacy of hyperbaric oxygen therapy has been questioned recently signifying poor understanding of the pathophysiology of the condition and therapies targeting the fibroatrophic process have become a focus of ORN treatment. Implementing recent IMRT radiation techniques has also shown evidence to reduce the incidence of ORN. This review provides an insight into the variations in definition and classification of the ORN, the controversies in its pathophysiology and the advances in the prevention and management.

The purpose of this paper is to map the number of concerns on the dimensions in Head and Neck Patient Concerns Inventory (PCI) on to the health utility (HU) index scores on Euroqol-Five Dimensions-Five levels {EQ-5D-5L) . This is a cross-sectional survey conducted in patients who have completed their treatment. Four candidate models were considered, three based on ordinary least squares regression (OLS) and one two-parts model. A reduced OLS model based on ‘Physical and functional’, ‘Treatment-related’, and ‘Psychological, emotional and spiritual well-being’ domains was found best on the estimation sample. This was validated externally on a separate sample. This is the first study that mapped a non-QOL tool to generate HU scores on EQ-5D-5L. The proposed mapping algorithm can estimate the cost–utility in economic evaluation studies when HU scores are not directly available. The algorithm will be best suited for studies in low-middle income countries.

This study was conducted to evaluate the outcomes of re-exploration procedures done after head and neck microvascular flap reconstructions. This is a retrospective review of 109 flaps in 106 patients (three patients had two flaps each) that underwent re-exploration procedures in 1001 consecutive free flap surgeries. The outcome was analysed in terms of the type of the flaps, re-exploration rate, flap salvage rate and overall flap success rate. Free radial forearm (RFF) was the commonest flap done (354, 35.3%). One hundred nine flaps underwent re-exploration procedures in 106 patients. Out of this, 79 flaps could be salvaged, and 30 flaps failed. There were also another ten flaps, which failed without any re-exploration. The overall re-exploration rate was 10.8%. The flap salvage rate was 72.4%. The overall flap success rate was 96.1%. Nearly three-fourths of the flaps with vascular compromise can be successfully salvaged with appropriate and timely intervention.

The purpose of the present study was to translate and culturally validate the University of Washington Quality of Life Questionnaire, Version 4.1 (UW-QOL v4.1) in Malayalam, a language commonly used in the state of Kerala in India. The tool underwent translation and adaptation. The translated instrument then underwent a pretest survey in 30 patients. The intention was to identify any problems with the questionnaire when applied to the participants and make any minor changes if required. This was followed by validation in 100 patients. The reliability was tested for internal consistency with Cronbach's alpha. Concurrent validity was tested by correlating it with the concurrently administered FACT-HN questionnaire scores. Construct validity was tested using 'Known-group validity.' Pretest survey did not identify any major problems. There was a moderate to strong correlation between the PF, SEF subscales and the composite scores on UW-QOL scores and the Head and Neck Cancer subscale and the FACT-H&N Total score. QOL scores were more in early staged patients and those who underwent no reconstructive procedure. This proved the construct validity. This study validates the Malayalam version of the UW-QOL instrument. It is reliable, valid and culturally adapted.

Background Trans-oral robotic surgery (TORS) and primary radiotherapy are the two modalities used to treat early T stage oropharyngeal squamous cell carcinoma(OPSCC). Prior literature including a recent randomized controlled trial have not shown the superiority of one modality over the other. When the modalities have similar outcomes, cost-effectiveness have an important role in deciding on the appropriate treatment. There are economic evaluations comparing the two modality with contradicting conclusions. The purpose of this review is to synthesise the evidence. Methods This is a systematic review of economic evaluations on the treatment modalities for OPSCC, namely TORS versus radiotherapy. The main outcome measures were the Cost-utility results reported as the effectiveness and costs separately and as part of the Incremental Cost-Effectiveness Ratio. Results Literature search identified five articles reporting cost-utility analysis, eligible for the review. A strategy is considered to be dominant when the effectiveness achieved was more at a lower cost, compared to the comparator. At the willingness to pay (WTP) threshold of 50,000 to 100,000 USD per Quality Adjusted Life-Year (QALY), three studies showed dominance of strategies in the base case analysis (TORS in two and Primary Chemoradiotherapy in one). Two of the articles studied node negative patients, one of them favored TORS. Three articles had node positive patients and two of them favored TORS and one favored chemoradiotherapy in the base case analysis. On sensitivity analysis, adjuvant treatment was found to be the detrimental factor affecting the cost-effectiveness. Conclusions TORS can be considered a cost-effective strategy in early T stage OPSCC, if the addition of adjuvant therapy involving radiotherapy can be avoided. Literature have shown that around 70% of the early cancers would require adjuvant treatment. This implies the importance of case selection while considering TORS as the initial treatment modality.

Introduction Salvage surgery is the treatment option in recurrences and second primary tumors. This paper aimed to study the options and outcomes of reconstruction and the predictors of poor reconstructive outcomes in salvage surgery for head and neck cancers. Study Design This is a retrospective study of all patients who underwent reconstructive flap surgery as part of salvage surgery for head and neck cancers between the years 2004 and 2017. Methods The initial treatment may be single modality radiotherapy or surgery or multimodality with combinations of surgery, radiotherapy, and chemotherapy. Any pathology that required surgical salvage was included. Any procedures done purely as reconstructive surgery were excluded. Predictor variables included demographical, clinical, and treatment factors. The outcome parameter was the occurrence of any flap-related complication or not. The complications and morbidity related to the procedures are reported Results Ninety-three patients underwent loco-regional flaps (LRF group), and 100 had free flaps (FF group). Pectoralis major flap was the commonest flap used in 68 patients (73.1%). Anterolateral thigh (ALT) flap was the commonest free flap and comprised 41% of the FF group. Any skin-related complication was seen in 35 patients (37.6%) and 41 (41%), respectively, in LRF and FF subsets. Any flap-related complication was seen in 16 patients (17.2%) and 29 patients (29%), respectively, in LRF and FF subsets. A summary measure “any one of the complications” was seen in 46 (49.5%) and 57 (57%), respectively, in LRF and FF subsets. Univariate and multivariate analysis for any flap-related complication identified no statistically significant predictor. Conclusions Soft tissue flaps were preferred in salvage reconstruction, though the defects had a bony component. In the microvascular free flap reconstruction era, pectoralis major flap has shifted its role from a “workhorse flap” to a “salvage flap.” About half of the patients develop some complications. Flap-related complications are also common. In salvage surgery, it is important that an appropriate flap is selected, suitable for the setting, according to the indications, neck, and patient conditions.

Background We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. Methods Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan–Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. Results All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. Conclusions The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.

Cholera is a severe diarrhoeal disease that spreads rapidly and affects millions of people each year, resulting in tens of thousands of deaths. The disease is caused byVibrio choleraeO1 and is characterized by watery diarrhoea that can be lethal if not properly treated. Cholera had not been reported in South America from the late 1800s until 1991, when it was introduced in Peru, wreaking havoc in one of the biggest epidemics reported to date. Within a year, the disease had spread to most of the Latin American region, resulting in millions of cases and thousands of deaths in all affected countries. Despite its aggressive entry, cholera virtually disappeared from the continent after 1999. The progression of the entire epidemic was well documented, making it an ideal model to understand cholera dynamics. In this review, we highlight how the synergy of socioeconomic, political and ecological factors led to the emergence, rapid spread and eventual disappearance of cholera in Latin America. We discuss how measures implemented during the cholera epidemic drastically changed its course and continental dynamics. Finally, we synthesize our findings and highlight potential lessons that can be learned for efficient and standardized cholera management programmes during future outbreaks in non-endemic areas.

BACKGROUND Partial pharyngeal defect reconstruction after total laryngectomy with regional and free fasciocutaneous flaps has been described. However, mucosal flaps for such defects have not been reported. METHODS An islanded facial artery musculo-mucosal (FAMM) flap was used to reconstruct a partial pharyngeal defect after total laryngectomy. Surgical, swallowing, and speech outcomes were analyzed at 6 months postoperatively. RESULTS At 6 months, videofluoroscopy showed no post swallow residue, fistula, trachea-esophageal puncture leak, or stricture. Perceptual analysis of recorded cold speech, native language passage sample, and the intelligibility analysis was good. The patient had normal mouth opening and marginal mandibular nerve function. CONCLUSION Islanded FAMM flap is ideal for partial pharyngeal defects, which cannot be closed primarily. Speech and swallowing outcomes were good. It provided a robust and predictable blood supply and adequate reach. There was no significant donor site morbidity. The musculo-mucosal flap replaced "like-with-like" tissue.

Tongue and buccal cancer carcinomas form the major bulk of oral cancers in the Indian subcontinent [1]. Although the diagnosis of tongue and buccal mucosa cancer is straight forward, a vast majority of patients present with locally advanced lesions. Several challenges exist in the management of oral cancer [2]. Standard management of oral cancers is surgical resection of the primary lesion and cervical lymph node dissection with the addition of radiation and/or chemotherapy as adjuvant therapy depending on the histopathological report. Along with the resection of the tumour, primary reconstruction is important to minimize morbidity. The tongue and buccal mucosa play an important role in speech and swallowing and reconstruction is performed to restore acceptable form and function [3]. Also, the reconstruction should be tailored in such a way to maximize the function of the remaining musculature and mucosa.

This study aimed to develop a speech intelligibility tool in Malayalam, an Indian language, based on the perceptual analysis. The tool had components of vowel, consonant, word, passage, and overall intelligibility. After face and content validation, a sample of 30 consecutive oral cancer patients underwent preliminary testing for internal consistency, inter- and intra-rater reliability, concurrent, and known-group validity. Subsequent validation was done in 80 T1–T4 patients from two centers. The scale had a high level of internal consistency; the Cronbach’s alpha was 0.847 and good intra-rater and inter-rater agreement amongst all raters. There was a strong correlation between the Malayalam and the English passage. Pearson correlation coefficient of 0.646 proved concurrent validity. On known-group and subsequent validation, the tool showed expected differences between the treatment groups. The speech tool proved to be reliable and valid for perceptual evaluation of speech intelligibility in oral cancer patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13193-020-01216-1) contains supplementary material, which is available to authorized users.

In oral squamous cell carcinoma (OSCC), expression of PDL1 is controversial with expressions showing a positive and negative correlation with survival in previous studies. Additionally, it is unclear whether expression on the tumour or tumour infiltrating lymphocytes (TIL) is a better predictor of survival. We performed this study on a cohort of Indian patients with OSCC to determine impact of PDL1 expression on survival. Retrospective analysis of 64 patients of OSCC treated with curative intent surgery with or without adjuvant therapy was performed. Stored tissue blocks were extracted and quantitative immunohistochemistry was performed for PDL1 expression separately on the tumour and the TIL using commercially available Dako kits. Correlation of clinical and pathological variables with PDL1 expression was performed using chi-square test. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards ratio. In our cohort, PDL1 expression was low, both in tumour (92% had

Objectives The AJCC 8th edition (AJCC 8) has introduced depth of invasion (DOI) and extranodal extension (ENE) into staging for oral squamous cell carcinoma (OSCC). Although validations have been performed on institutional datasets have shown a good performance, particularly in early OSCC, there have been no studies on diverse patient populations that determine the impact on prognostic heterogeneity. Materials and methods Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery +/- adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) as endpoint, the prognostic performance of AJCC 7th and 8th editions were compared using Akaike Information Criterion (AIC), Bayesian Information Criteria (BIC), Harrell's concordance index (C-index). Results When comparing AJCC 8 to AJCC 7, the heterogeneity in prediction of OS increased for T-category and N-category while remaining unchanged for TNM staging, suggesting AJCC 8 increased complexity with no improvement in predictive value. There were significant differences in median DOI and incidence of ENE between geographical regions, resulting in dissimilar rates of stage-migration when adopting AJCC 8. Conclusion In an attempt to improve prognostic performance, AJCC 8 introduced more variables; however heterogeneity in these results in significant geographical differences in model discrimination and performance. Caution should be applied as this may result in inaccurate and unreliable prognostic predictions that may impact treatment recommendations.

Sinonasal cancers form a distinct subset of head-and-neck tumors. They exhibit varied histologies with different clinical outcomes. These tumors are rare, and there exists no randomized trial identifying the ideal treatment for these patients. Induction chemotherapy (CT) has been tried with varying success for different purposes such as bioselection, improving outcomes, orbital preservation, and reduction in the extent of surgery. The purpose of this review is to examine and present the literature regarding the use of induction CT in sinonasal cancers and their outcomes.