Association of race and gender with primary caregiver relationships and eligibility for advanced heart failure therapies.

BACKGROUND: Caregiver support is considered necessary after heart transplant (HT) and left ventricular assist device (LVAD) for patients with end-stage heart failure (HF). Few studies have demonstrated how caregivers differ by gender and race, and whether that impacts therapy eligibility. METHODS: We examined caregiver relationships among 674 patients (32% women, 55% Black) evaluated at Emory University from 2011 to 2017. Therapy readiness was assessed using the Stanford Integrated Assessment for Transplant (SIPAT). Evaluation outcome according to caregiver relationship was compared using χ2 analysis. Multivariable logistic regression determined the association between caregiver and eligibility according to gender and race. RESULTS: Women and Black patients were less likely to have spouses as their support person (P < .001). Women were less likely to be considered eligible for advanced therapies (adjusted odds ratio [aOR] .64, 95% confidence interval [CI] .46-.89; P = .008), with Black women having lower eligibility than White women (aOR .28, 95% CI .11-.72; P = .008). Social support and SIPAT scores did not significantly influence eligibility by gender or race. CONCLUSION: Lack of caregiver support is considered a relative contraindication to advanced therapies. Type of caregiver in our cohort varied according to race and gender but did not explain differences in eligibility for advanced therapies.

Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis.

Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5 months. The median radiation dose used was 60 Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27 months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50 Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.

Sex differences in eligibility for advanced heart failure therapies.

OBJECTIVES: We investigated sex-based differences in eligibility for and outcomes after receipt of advanced heart failure (HF) therapies. BACKGROUND: Although women are more likely to die from HF than men, registry data suggest that women are less likely to receive heart transplant (HT) or left ventricular assist device (LVAD) for largely unknown reasons. METHODS: We performed a single-center retrospective cohort study of patients evaluated for advanced HF therapies from 2012 to 2016. Logistic regression was used to determine the association of sex with eligibility for HT/LVAD. Competing risks and Kaplan-Meier analysis were used to examine survival. RESULTS: Of 569 patients (31% women) evaluated, 223 (39.2%) were listed for HT and 81 (14.2%) received destination (DT) LVAD. Women were less likely to be listed for HT (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.21-0.61; P < .0001), based on allosensitization (P < .0001) and obesity (P = .02). Women were more likely to receive DT LVAD (adjusted OR 2.29, 95% CI 1.23-4.29; P = .01). Survival was similar between men and women regardless of whether they received HT and DT LVAD or were ineligible for therapy. CONCLUSION: Women are less likely to be HT candidates, but more likely to receive DT LVAD.

Validating patient prioritization in the 2018 Revised United Network for Organ Sharing Heart Allocation System: A single-center experience.

The 2018 Revised United Network for Organ Sharing Heart Allocation System (HAS) was proposed to reclassify status 1A candidates into groups of decreasing acuity; however, it does not take into account factors such as body mass index (BMI) and blood group which influence waitlist (WL) outcomes. We sought to validate patient prioritization in the new HAS at our center. We retrospectively evaluated patients listed for heart transplantation (n = 214) at Emory University Hospital from 2011 to 2017. Patients were reclassified into the 6-tier HAS. Multistate modeling and competing risk analysis were used to compare outcomes of transplantation and WL death/deterioration between new tiers. Additionally, a stratified sensitivity analysis by BMI and blood group was performed. Compared with tier 4 patients, there was progressively increasing hazard of WL death/deterioration in tier 3 (HR: 2.52, 95% CI: 1.37-4.63, P = .003) and tier 2 (HR: 5.03, 95% CI: 1.99-12.70, P < .001), without a difference in transplantation outcome. When stratified by BMI and blood group, this hierarchical association was not valid in patients with BMI ≥30 kg/m2 and non-O blood groups in our cohort. Therefore, the 2018 HAS accurately prioritizes the sickest patients in our cohort. Factors such as BMI and blood group influence this relationship and iterate that the system can be further refined.

De novo DQ donor-specific antibodies are associated with worse outcomes compared to non-DQ de novo donor-specific antibodies following heart transplantation.

BACKGROUND: Antibody-mediated rejection (AMR) resulting from de novo donor-specific antibodies (dnDSA) leads to adverse outcomes following heart transplantation (HTx). It remains unclear what role dnDSA to specific HLA antigens play in adverse outcomes. This study compares outcomes in patients developing dnDSA to DQ antigens with those developing non-DQ dnDSA and those free from dnDSA. METHODS: The present study was a single-center, retrospective analysis of 122 consecutive HTx recipients. The primary outcome was a composite of death or graft dysfunction. RESULTS: After 3.3 years of follow-up, 31 (28%) patients developed dnDSA. Mean time to dnDSA was 539 days. Of 31 patients, 19 developed DQ antibodies and 12 developed non-DQ antibodies. Compared to non-DQ dnDSA, DQ antibodies presented with higher MFI values (P=.001) were more likely persistent (P=.001) and appeared later post-HTx (654 vs 359 days, P=.035). In a multivariable analysis, DQ dnDSA was associated with increased risk of the primary endpoint (HR 6.15, 95% CI 2.57-14.75, P=.001), whereas no increased risk was seen with non-DQ dnDSA (P=.749). CONCLUSIONS: dnDSA to DQ antigens following HTx are associated with increased risk of death and graft dysfunction.

Improved Outcomes for Women on the Heart Transplant Wait List in the Modern Era.

BACKGROUND: Whether the routine use of continuous-flow left ventricular assist devices (LVAD) has affected gender differences in outcomes for patients listed for heart transplantation (HT) is unclear. METHODS AND RESULTS: We identified 20,468 adults (25% women) listed as status 1A or 1B for HT from 2000 to 2014. Sex differences in removal from the wait list during the first 365 days due to death or deterioration was assessed with the use of Kaplan-Meier survival analysis. Patients were stratified according to listing before (era 1) or after (era 2) Food and Drug Administration approval of the Heartmate II LVAD on April 22, 2008. Freedom from death or deterioration on the wait list was higher for men than for women (70% vs 64%; P < .001). After adjusting for risk factors, women had a higher risk of removal from the wait list at 365 days during both era 1 (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.10-1.36; P < .001) and era 2 (HR 1.15, 95% CI 1.01-1.31; P = .029). Further adjustment for LVAD use eliminated the higher risk for women in era 2 (HR 1.14, 95% CI 0.99-1.29; P = .053) and not in era 1 (HR 1.22, 95% CI 1.10-1.36; P < .001). CONCLUSIONS: The higher risk for death or deterioration in women waiting for HT has improved in the modern era.

Treatment results in advanced stage Hodgkin's lymphoma: a retrospective study.

BACKGROUND: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. AIM: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. MATERIALS AND METHODS: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. RESULTS: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. CONCLUSIONS: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

Prospective observational study on diagnostic accuracy of whole-body MRI in solid small round cell tumours.

AIM: To assess the diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) for metastatic disease in patients with solid small round cell tumours (SRCT) by comparing it with routine staging procedures (standard of care). MATERIALS AND METHODS: Eligible cases of neuroblastoma, primitive neuroectodermal tumour, and rhabdomyosarcoma were enrolled in the study after obtaining informed consent. WB-MRI was undertaken using overlapping coronal T1 and short-tau inversion recovery (STIR) sequences. Lesions were classified into skeletal, pulmonary, and soft-tissue types. Conventional staging, which consisted of combined positron-emission tomography & computed tomography (PET-CT), bone scintigraphy & bone marrow biopsy for bone metastases, CT thorax for lung metastases, combined PET-CT, metaiodobenzylguanidine (MIBG) scintigraphy (in neuroblastoma) for soft tissue metastases and clinical evaluation was used as the reference standard. Parameters for diagnostic accuracy were calculated. RESULTS: Thirty-four out of forty patients enrolled were included in final analysis, half of them having metastatic disease. The sensitivity, specificity, positive and negative predictive value, and the diagnostic accuracy of WB-MRI and PET-CT for skeletal metastases as compared to reference standard were 91.9%, 99.8%, 97.4%, 99.6%, and 95.5% and 99.1%, 99.9%, 99.1%, 99.9%, and 99.9%, respectively. The sensitivity of MRI, only PET and PET-CT with plain CT thorax was 30%, 40%, and 100%, respectively, for lung metastases. The sensitivity of MRI for soft-tissue lesions was 76.9%. CONCLUSION: WB-MRI is a radiation-free tool with high diagnostic accuracy for the evaluation of metastatic disease to the marrow. The rate of detection of soft-tissue metastases, such as nodal metastases, is less when WB-MRI is compared with conventional staging using coronal STIR images. CT thorax is essential for accurate evaluation of lung metastases.

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells.

Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1ß, PDGF-AA, TGF-ß1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1ß, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent decrease in clonogenic survival. In conclusion, present study revealed the similarities and subtle differences in basal and radiation-induced cytokine profile of different tumor cell lines, and its influence on growth and survival of respective bystander cells. These findings may add a new dimension to our current understanding about role of cytokines in cancer biology.

Understanding the principles in management of Wilms' tumour: can imaging assist in patient selection?

The management of Wilms' tumour has evolved through thorough systematic research, predominantly lead by two groups: the Wilms' Tumour Study Committee of the International Society of Paediatric Oncology (SIOP) and National Wilms' Tumor Study Group (NWTSG) of North America. These two groups differ in their approach: SIOP advocates initial chemotherapy of 4-6 weeks followed by surgery, whereas the NWTSG advocates upfront surgery, with certain exceptions. This review briefly discusses the principles, and pros and cons of each approach. Both the treatment approaches have equivalent outcomes (in the form of event-free survival and overall survival), when compared stage-wise. With this knowledge, modern imaging can be used for individualizing treatment in anticipation of minimizing complications. The review identifies critical imaging features and discusses the reliability of imaging based on current reports in the literature.

Brachytherapy for Organ and Function Preservation in Soft-Tissue Sarcomas in Adult and Paediatric Patients.

Adjuvant radiotherapy is an integral component in the management of soft-tissue sarcomas. Brachytherapy is a very convenient and conformal way of delivering adjuvant radiotherapy in such tumours, which spares the surrounding normal tissue. Randomised studies have established the efficacy of brachytherapy in the adjuvant setting, with a 5-year local control of 80-85%. High dose rate, low dose rate and pulsed dose rate have shown equivalent local control, but high dose rate has gained popularity owing to patient convenience, radiation safety and flexibility in dose optimisation. Freehand insertion perioperative brachytherapy (intraoperative placement and postoperative treatment) is the most commonly used technique in soft-tissue sarcomas, with intraoperative radiotherapy and radioactive seed placement being the less commonly used techniques. Brachytherapy can be used as monotherapy or in combination with external beam radiotherapy, such as in cases of close/positive margins for safe dose escalation. Although the quantum of side-effects with external beam radiotherapy has considerably reduced with the evolution of technology and the introduction of intensity modulation (intensity-modulated radiotherapy), brachytherapy still scores better in terms of dose conformality, especially in recurrent tumours (previously irradiated) and when used to treat paediatric and geriatric patients.

Non-surgical organ preservation in laryngeal and hypopharyngeal cancers: an audit from the clinic.

BACKGROUND: There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. METHOD: This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). RESULTS: Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. CONCLUSION: Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.

Results of surgical resection in pelvic Ewing's sarcoma.

OBJECTIVE: To evaluate the results of patients with non-metastatic Ewing's sarcoma of the pelvis treated with surgical resection as part of their multimodality treatment METHODS: Twenty-six patients treated between September 2000 and September 2009 were evaluated. Thirteen resections included the acetabulum and 13 did not. Thirteen resections excluding the acetabulum had no reconstruction. Arthrodesis was done in two, extracorporeal radiation and reimplantation in two, and pseudarthrosis in nine patients. RESULTS: Three patients had involved margins. Seventeen patients had good response to chemotherapy and nine were poor responders. Twenty-one patients were available for follow-up. The follow-up ranged from 4 to 129 months (mean 36 months). Thirteen patients are currently alive. There was one local recurrence. On Kaplan-Meier analysis the overall survival was 72% at 5 years. The 3-year survival in good responders to chemotherapy was 94% compared to 30% in poor responders. The Musculoskeletal Tumor Society Score ranged from 23 to 29, with patients in whom the acetabulum was retained having better function compared to patients in whom acetabulum was resected. CONCLUSION: Surgery provides good local control and oncologic outcomes with acceptable function in these patients.

Effect of incorporation of soy protein isolate and inulin on quality characteristics and shelf-life of low-fat duck meat sausages.

OBJECTIVE: Low fat duck meat sausages were prepared by replacing the fat in the formulations with soy protein isolate (SPI) and inulin to find the best formulation having superior shelflife without affecting its quality attributes. METHODS: Four sausage mix formulations were prepared viz.control (0% SPI and inulin), T1 (2.5% inulin), T2 (2.5% SPI), and T3 (2.5% SPI+2.5% inulin) replacing duck fat as per the recipe. Five batches of duck meat sausages of each formulation were prepared, and the final products were evaluated for physico-chemical, organoleptic, and microbiological qualities. RESULTS: The % moisture and crude protein content of the sausages revealed an increasing trend (p<0.01) from control to the treated formulations, while the % total ash contents were found to be non-significant (p>0.05). On the contrary, the per cent ether extract decreased significantly (p<0.01) from the control to the treated groups. In terms of calorie value, control samples exhibited the highest values with a significant (p<0.01) regression from control to treated formulation, respectively. The colour profile study (L, a*, b*) of the formulations were found to be non-significant. Texture profile study in terms of springiness, cohesiveness, chewiness, and resilience revealed no significant difference in all the treatment groups except the hardness scores, which revealed a significantly (p<0.01) increasing trend from control to the treated formulations. The total viable count showed a significant decrease in the treated groups. However, there was a significant increase in the bacterial load during the storage till day 15th. The total viable psychrophilic bacterial count showed a significant (p<0.01) increase in bacterial load from day 5th to 15th day of storage. Colititre counts were negative for all the formulations until the 15th day of storage. CONCLUSION: The present study results may conclude that duck meat sausages could be prepared satisfactorily by replacing duck fat with SPI and inulin at the rate of 2.5% of each with superior quality attributes.

Outcomes of surgical versus non-surgical treatment of resectable T4a laryngeal and hypopharyngeal carcinoma.

OBJECTIVE: Surgery is the recommended treatment for resectable T4a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients. METHOD: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T4a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes. RESULTS: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment. CONCLUSION: Surgery is the preferred treatment for T4a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

Cytomegalovirus prostatitis in a heart transplant recipient.

Cytomegalovirus (CMV) is the most common viral infection affecting the posttransplantation course of organ recipients. However, CMV involvement of the prostate even in immunocompromised hosts is rare. We describe the first case in the heart transplant literature of a 59-year-old heart recipient with CMV prostatitis. An elevated PSA prompted a prostate biopsy revealing an adenocarinoma, chronic prostatitis as well as viral cytopathic effect consistent with CMV infection. CMV PCR in the blood was negative. A few months prior, the patient developed CMV viremia and was treated initially with ganciclovir intravenously and subsequently with valganciclovir and CMV immunoglobulins. The patient did well with brachytherapy and additional anti-CMV agents. We discuss the role of CMV in the prostate and management of CMV prostatitis. Relationships between CMV, prostate cancer and heart transplantation are also outlined.

A unified approach to design controller in cascade control structure for unstable, integrating and stable processes.

This article presents a unified approach of controller design in cascade control structure (CCS) for unstable, integrating and stable processes with dead-time to achieve enhanced load disturbance rejection. The design of inner and outer loop controllers in CCS is based, partially on the direct synthesis approach and partially on the pole placement method. First, the parameters of the inner loop controller are obtained and then the outer loop controller is designed by considering the inner loop as a part of the primary plant. The proposed design approach deals with a wide range of processes having unstable, integrating and stable dynamics in a unified way. It is applied directly on the higher and lower order processes, as the proposed strategy is acquitted from the approximation of the dead-time and model order reduction of the plant. Simulations have been conducted to show the efficacy of the present approach. The results shows that the present approach provides enhanced regulatory performance as compared to the recently reported approaches from the literature.