Optimising head and neck cancer patient management: the crucial contributions of multidisciplinary tumour board decision-making.

Introduction: Squamous cell carcinoma (SCC) of the head and neck is a great burden globally, which is being tackled through treatment options of surgery, radiation therapy, chemotherapy, or a combination of these, to avoid disease-related mortality. Multidisciplinary tumour boards play a pivotal role in customising and deciding management plan based on clinical aspects. The objective of the study is to determine the concordance of opinion between the treatment plan of a primary physician and board members. Material and methods: This is a retrospective cross-sectional study that includes 137 head and neck carcinoma cases. They were discussed in the multidisciplinary tumour board meeting and were reviewed; all demographics were analysed including the tumour staging and the decisions of the primary physician was compared with those of the board. To check the concordance between primary surgeon plans or after board discussion Kappa agreement test was used. Results: Total of 137 patients were included in the study out of which 63 cases were pre-treatment and 74 cases were post-treatment, i.e., surgically treated cases, with the distribution being 46% and 54%, respectively. Most cases, totaling 120, were SCC, accounting for 80% of the total cases. Among the pre-treatment cases, T4a and N0 were the most common categories, with 29 and 40 cases, respectively. Similarly, in post-treatment cases, the majority fell into the T4a and N1 categories, with 29 and 38 cases, respectively. When comparing the primary surgeon's plan with the tumour board meeting decision, the agreement showed a value of 0.273, indicating a slight level of agreement between the two entities. Conclusion: Our data indicates that the multidisciplinary head and neck tumour board may have influenced the treatment plans of the primary surgeon, in approximately one in two patients (43.06%).

Comparative whole-genome transcriptome analysis in renal cell populations reveals high tissue specificity of MAPK/ERK targets in embryonic kidney.

BACKGROUND: MAPK/ERK signaling is a well-known mediator of extracellular stimuli controlling intracellular responses to growth factors and mechanical cues. The critical requirement of MAPK/ERK signaling for embryonic stem cell maintenance is demonstrated, but specific functions in progenitor regulation during embryonic development, and in particular kidney development remain largely unexplored. We previously demonstrated MAPK/ERK signaling as a key regulator of kidney growth through branching morphogenesis and normal nephrogenesis where it also regulates progenitor expansion. Here, we performed RNA sequencing-based whole-genome expression analysis to identify transcriptional MAPK/ERK targets in two distinct renal populations: the ureteric bud epithelium and the nephron progenitors. RESULTS: Our analysis revealed a large number (5053) of differentially expressed genes (DEGs) in nephron progenitors and significantly less (1004) in ureteric bud epithelium, reflecting likely heterogenicity of cell types. The data analysis identified high tissue-specificity, as only a fraction (362) of MAPK/ERK targets are shared between the two tissues. Tissue-specific MAPK/ERK targets participate in the regulation of mitochondrial energy metabolism in nephron progenitors, which fail to maintain normal mitochondria numbers in the MAPK/ERK-deficient tissue. In the ureteric bud epithelium, a dramatic decline in progenitor-specific gene expression was detected with a simultaneous increase in differentiation-associated genes, which was not observed in nephron progenitors. Our experiments in the genetic model of MAPK/ERK deficiency provide evidence that MAPK/ERK signaling in the ureteric bud maintains epithelial cells in an undifferentiated state. Interestingly, the transcriptional targets shared between the two tissues studied are over-represented by histone genes, suggesting that MAPK/ERK signaling regulates cell cycle progression and stem cell maintenance through chromosome condensation and nucleosome assembly. CONCLUSIONS: Using tissue-specific MAPK/ERK inactivation and RNA sequencing in combination with experimentation in embryonic kidneys, we demonstrate here that MAPK/ERK signaling maintains ureteric bud tip cells, suggesting a regulatory role in collecting duct progenitors. We additionally deliver new mechanistic information on how MAPK/ERK signaling regulates progenitor maintenance through its effects on chromatin accessibility and energy metabolism.

Proteomics approaches to characterize the immune responses in cancer.

Despite the dynamic development of cancer research, annually millions of people die of cancer. The human immune system is the major 'guard' against tumor development. Unfortunately, cancer cells have the ability to evade the immune system and continue to grow. The proper understanding of the intricate immune response in tumorigenesis remains the holy grail of cancer immunology and designing effective immunotherapy. To decode the immune responses in cancer, in recent years, proteomics studies have received considerable attention. Proteomics studies focus on the detection and quantification of proteins, which are the effectors of biological functions, and as such, are proven to reflect the cell state more accurately, in comparison to genomic or transcriptomic studies. In this review, we discuss the proteomics studies applied to characterize the immune responses in cancer and tumor immune microenvironment heterogeneity. Further, we describe emerging single-cell proteomics approaches that have the potential to be applied in cancer immunity studies.

Risk factors associated with disease recurrence in patients with T4 staged Squamous Cell Carcinoma of the Oral Cavity treated with surgery and postoperative radiotherapy.

Objective: To determine the association of clinical and pathological parameters on recurrence of treated stage T4squamous cell carcinoma of oral cavity patients managed with surgery followed by concomitant chemo and radiation therapy. METHODS: The retrospective, cohort study was conducted at Patel Hospital, Karachi, and comprised data of patients diagnosed with oral squamous cell carcinoma and admitted between January 1, 2014, and January 30, 2019. Patients of either gender aged 20-80 years who had a minimum follow-up of one year were included. Data was collected using the Head and Neck Cancer registry form and the medical record files. The subjects were also contacted by telephone when needed. The study end-points were disease-free survival and overall survival. Data was analysed using SPSS 21. RESULTS: Out of the 83 patients, 65(78%) were male. The overall median(range) age was 46(20-80) years, and 43(52%) of them were aged 31-50 years. Overall, 15(18%) patients had positive margins and 48(58%) had proven cervical node metastasis on histopathology. Overall survival was 42.2% with the median(range) follow-up time was 14(9-21) months and 5-year disease-free survival was 45.8% with the median (range) follow-up time was 13(7-19). The factor that affected the final outcome was found to be the increasing nodal ratio (p=0.043). Conclusion: Among T4 oral squamous cell carcinoma patients treated with surgery and adjuvant therapy, the rate of disease recurrence was found to be high. Tumours with a high cervical nodal disease burden and/or margin involved were at substantially higher risk of recurrence.

To assess the aggressiveness of oral squamous cell carcinoma in the young population.

Objectives: To assess the recurrence and disease-free survival in oral squamous cell carcinoma patients, and to compare them between two age groups. METHODS: Data were extracted from Patel hospital cancer registry database of patients admitted from January 1st2008 to December 31st 2018 based on retrospective diagnosed with oral squamous cell carcinoma. Patient stratified in to two groups i.e. patients with less than or more than 40 years. Various etiological factors, staging, treatment, site of the tumor and recurrence and mortality were assessed. RESULTS: Of the 450 patients, 124(27.5%) were in group A and 327(72.5%) were in group B. There were 101(81%) males in group A and 240(73.4%) males in group B. The overall mean age was 43.63±10.75 years (range: 22-70 years). The most common site of the tumour was cheek 232(51.5%). Recurrence of tumour was 45(36%) in group A and 120(37%) in group B (p=0.653). Overall mortality in group A was 67(54%) compared to 168(51%) in group B (p=0.811). CONCLUSIONS: Mortality and disease recurrence in both age groups was almost the same. Cheek was the most common site of presentation.

Role of contrast enhanced computed tomography in assessing cervical lymph node metastases in oral cavity squamous cell carcinoma.

OBJECTIVE: To evaluate the diagnostic accuracy of contrast-enhanced computed tomography scan in detecting cervical nodal metastasis in oral cavity squamous cell carcinoma. METHODS: The retrospective cross-sectional study was conducted at Aga Khan University Hospital, Karachi, Pakistan. and comprised records from January 1, 2015, to October 31, 2016, of patients diagnosed with oral cavity squamous cell carcinoma and who underwent surgical resection of primary tumour along with neck dissection after having a contrast-enhanced computed tomography scan of head and neck. Diagnostic accuracy of the scans was calculated using final histopathology as the gold standard. All scans were reviewed by a consultant radiologist. Data was analysed using SPSS 23. RESULTS: Of the 100 patients whose records were reviewed, 70(70%) were female, 55(55%) had buccal and 32(32%) had tongue cancer.. The scans had sensitivity 83%, specificity 61.7%, positive predictive value 70.9%, negative predictive value 76.3% and overall diagnostic accuracy 73%. CONCLUSIONS: Computed tomography scan was found to be a useful tool for preoperative staging of oral cavity squamous cell carcinoma. However, due to low specificity and negative predictive value, elective neck dissection should still be done in a negative scan for cervical lymph node metastases.

A rare case of three years disease free survival in a locally advanced parathyroid carcinoma successfully excised by complete surgical resection.

Parathyroid carcinoma (PC) is one of the rarest malignancies making approximately 0.005% of all cancers. It may arise sporadically or less commonly, in conjunction with genetic endocrine syndromes. Due to the rarity of the disease, no general consensus or definitive guidelines exist for its pre-operative diagnosis, management, or follow up. Surgical tumor removal is the gold standard treatment to prevent its recurrence. Parathyroid carcinoma has a high recurrence rate ranging from 40 to 60% in recent literature. We report a case of a seventy-year-old elderly female with locally advanced parathyroid carcinoma successfully surgically excised completely with a 3 year disease free survival period without adjuvant chemotherapy or radiotherapy.

Identification and Characterization of Splicing Defects by Single-Molecule Real-Time Sequencing Technology (PacBio).

Although DNA-sequencing is the most effective procedure to achieve a molecular diagnosis in genetic diseases, complementary RNA analyses are often required.Reverse-Transcription polymerase chain reaction (RT-PCR) is still a valuable option when the clinical phenotype and/or available DNA-test results address the diagnosis toward a gene of interest or when the splicing effect of a single variant needs to be assessed.We use Single-Molecule Real-Time sequencing to detect and characterize splicing defects and single nucleotide variants in well-known disease genes (DMD, NF1, TTN). After proper optimization, the procedure could be used in the diagnostic setting, simplifying the workflow of cDNA analysis.

Improving Anemia in Inflammatory Bowel Disease: Impact of the Anemia Care Pathway.

BACKGROUND: Anemia is a common complication of inflammatory bowel disease (IBD). Despite existing guidelines for anemia in IBD, it is frequently under-treated and the prevalence of anemia has remained high. To address this gap, the Crohn's and Colitis Foundation developed the Anemia Care Pathway (ACP). AIMS: To implement the ACP in a managed care setting and identify where it improves practice habits and where barriers remain. METHODS: The ACP was implemented from July 2016 through June 2017 and retrospectively studied. Run charts were used to identify shifts in iron deficiency screening and treatment as well as anemia prevalence. Results were compared to those of other providers in the same center not using the ACP. RESULTS: 640 IBD encounters were studied. In the ACP clinic (n = 213), anemics received iron therapy in only 30% of encounters at baseline but improved to 80%. Concurrently, anemia prevalence decreased from 48 to 25%. Screening for iron deficiency, however, did not improve. No shifts were seen in the non-ACP clinics (n = 427) across the same period despite awareness of the ACP and other guidelines. CONCLUSIONS: Across 1 year, we observed gaps in the screening and treatment of anemia in IBD. Although screening rates did not improve, the ACP appeared to reduce missed opportunities for iron therapy by about half. Most importantly, this was associated with an overall decrease in anemia prevalence. Future refinements to the ACP should be focused on enhanced screening and follow-up.

Calcifying fibrous pseudotumour of maxilla: A rare entity mimicking malignancy: A case report.

Occurrence of inflammatory pseudotumour in head and neck region or nose and paranasal sinuses is rare. However, when they do occur, they could be quite aggressive. Etiologically, they are believed to be reactive than neoplastic, and calcification may suggest end-stage. Their clinical presentation and radiologic features may resemble a malignancy. Grossly, they are not encapsulated, but multilobulated and can be circumscribed or infiltrative. Histologically, they constitute of bland spindle cells with scant cytoplasm and occasional mitotic figures. Scattered lymphocytic and plasma cell infiltrates with abundant dense hyalinized collagenous stroma and focal small calcifications are seen. Presence of atypia, DNA aneuploidy, and abnormal p53 expression may suggest malignant potential. Though not known to metastasize, they can lead to local complications, causing destruction of bone and surrounding tissues. Management is mainly by surgical excision though adjunct corticosteroids have been advocated. We report such a rare case of calcifying fibrous pseudotumour of maxilla.

Effectiveness of plain X-ray in detection of fish and chicken bone foreign body in upper aerodigestive tract.

OBJECTIVE: To assess the use of plain film radiology in the detection of fish and chicken bones in the upper aerodigestive tract. METHODS: This retrospective chart review was conducted at the Aga Khan University Hospital, Karachi, and comprised medical charts of patients who had undergone oesophagoscopy for removal of fish and chicken bone from 1990 to 2015.SPSS 19 was used for data analysis. RESULTS: Of the 24 patients, foreign body was detected on X-ray in 7(29.2%) and through fibre optic laryngoscopy in 13(54.2%).All the patients underwent surgical intervention for removal of the foreign body. Also, 19(79.2%) patients underwent direct laryngoscopy and 5(16.7%) required oesophagoscopy. The sensitivity with X-ray was 15% and specificity was zero. The sensitivity of fibre optic laryngoscopy in comparison to intra-operative findings was 65% and the specificity was 100%. CONCLUSIONS: X-ray was not found to be an ideal modality to diagnose fish or chicken bone impaction in the upper aerodigestive tract.

Evolution of sinonasal symptoms and mucosal healing after minimally invasive pituitary surgery.

BACKGROUND: Minimally invasive pituitary surgery (MIPS) via endoscopy has become widely accepted as the surgical paradigm of choice for pituitary pathology. The objective of the current study was to analyze the evolution of symptom scores and mucosal healing after MIPS. METHODS: The 22-item Sino-Nasal Outcome Test (SNOT-22) scores and objective endoscopic data of 52 patients were reviewed in a longitudinal manner. Scaled averages of the SNOT-22 and endoscopic scores from different time points were compared with baseline scores by using nonparametric testing. The time to baseline for endoscopic examinations was also analyzed by using Kaplan-Meier curves. RESULTS: The rhinologic symptoms subdomain of the SNOT-22 scores showed statistically significant worsening between baseline and 2 weeks after surgery (p = 0.03). Follow-up SNOT-22 scores after 2 weeks showed no significant differences compared with baseline scores, with an overall trend toward improvement in patient symptoms during the subsequent period. Similar analysis for the endoscopic data illustrated statistically significant differences from the baseline scores up to 16 weeks after surgery. The overall trend showed a worsened endoscopic examination, initially with a spike at ∼8 to 10 weeks (p = 0.03) and with a subsequent return to baseline. The Kaplan-Meier estimate curve demonstrated a median time to return to baseline endoscopy at 18.9 weeks (95% confidence interval, 14.9-38.3 weeks). CONCLUSION: The longitudinal data exhibited subjective improvement of patient outcomes based on SNOT-22 scores within 2-4 weeks after MIPS. However, the objective endoscopic data revealed a lag in improvement of the examination, typically at 16-20 weeks, which underscores ongoing careful endoscopic assessment and management to ensure proper mucosal healing beyond just subjective symptoms as the gauge to postoperative recovery.

Nuclear transportation of exogenous epidermal growth factor receptor and androgen receptor via extracellular vesicles.

Epidermal growth factor receptor (EGFR) plays a central role in the progression of several human malignancies. Although EGFR is a membrane receptor, it undergoes nuclear translocation, where it has a distinct signalling pathway. Herein, we report a novel mechanism by which cancer cells can directly transport EGFR to the nucleus of other cells via extracellular vesicles (EVs). The transported receptor is active and stimulates the nuclear EGFR pathways. Interestingly, the translocation of EGFR via EVs occurs independently of the nuclear localisation sequence that is required for nuclear translocation of endogenous EGFR. Also, we found that the mutant receptor EGFRvIII could be transported to the nucleus of other cells via EVs. To assess the role of EVs in the regulation of an actual nuclear receptor, we studied the regulation of androgen receptor (AR). We found that full-length AR and mutant variant ARv7 are secreted in EVs derived from prostate cancer cell lines and could be transported to the nucleus of AR-null cells. The EV-derived AR was able to bind the androgen-responsive promoter region of prostate specific antigen, and recruit RNA Pol II, an indication of active transcription. The nuclear-translocated AR via EVs enhanced the proliferation of acceptor cells in the absence of androgen. Finally, we provide evidence that nuclear localisation of AR could occur in vivo via orthotopically-injected EVs in male SCID mice prostate glands. To our knowledge, this is the first study showing the nuclear translocation of nuclear receptors via EVs, which significantly extends the role of EVs as paracrine transcriptional regulators.

Learning curve for the transsphenoidal endoscopic endonasal approach to pituitary tumors.

INTRODUCTION: The transsphenoidal endoscopic approach is a relatively new procedure compared to the microscopic approach in pituitary adenoma resection. The endoscopic approach has shown to significantly decrease the rate of complications, time in the operating room and hospital, and patient post-op discomfort. However, this procedure requires the surgeon to make use of different visual and tactile clues that must be developed with experience. Therefore, it is important to understand the learning curve that the surgeon must overcome to become proficient with the endoscopic approach. METHODS: Retrospective review of a single-surgeon consecutive series of 78 patients undergoing endoscopic pituitary tumor surgery from 2006 to 2012 at Rush University Medical Center has been used in this study. Patients were grouped according to an early (n = 9) and late group (n = 68) determined by a significant difference in outcomes. Our primary outcome measures were: duration of operation, CSF leak, hospital length of stay, visual field improvement, diabetes insipidus, panhypopituitarism, and subtotal resection. RESULTS: There was a significant reduction in OR time and intraoperative CSF leaks between the early and late groups. There was no difference in hospital LOS or visual field improvement between the groups. With regards to complication rates, there was no difference found for DI, panhypopituitarism, lumbar drain placement, sinusitis, or subtotal resection between the two groups. CONCLUSION: This study indicates that there may be a learning curve of approximately 9 cases before a surgical team can decrease OR times and reduce the rate of intraoperative CSF leaks for the endonasal endoscopic approach to pituitary adenoma resection.

Is There Any Benefit of Drain Placement on Postoperative Complications in Patients Undergoing the Sistrunk Procedure?

Introduction Same-day, outpatient Sistrunk procedure is commonly performed to manage thyroglossal duct cyst anomalies and may lead to postoperative complications. Surgical drains are placed to prevent complications, but recent observations show no advantage and rather increased health care costs and patient discomfort. Objective The study evaluated if drain placement in the Sistrunk procedure offers any benefit on postoperative complications. Methods A retrospective analysis of patient records having undergone same-day, outpatient Sistrunk procedure from 2004 to 2014 was done. Of 58 (38 male and 20 female) patients included, 38 did not have drains placed and the remaining 20 had drains placed. Mean and median age of patients was 18.1 and 13.5 years, respectively. Postoperative complications of patients with drains versus those without drains were statistically analyzed. Results Overall, about 10% of patients had hematoma/seroma (H-S), with 6.9% of patients needing aspiration for H-S; 3.4% had wound infections; and 1.7% had pus formation. No statistically significant differences in Sistrunk-related complications between patient groups (with drain or without drain) were seen using Fisher exact (two-sided) test: H-S (p = 0.08); need for aspiration (p = 0.29); wound infection (p > 0.05); and pus formation (p = 0.35). Chi-square test also did not show any significant difference in the groups in terms of number of follow-ups. Conclusion Surgical placement of a drain in the Sistrunk procedure does not seem to offer any advantage in terms of reducing common postoperative complications. Sameday Sistrunk procedure without any drain placement may be a safer alternative without necessitating hospitalization. More studies with larger sample size are needed for further substantiation.(AU)

Is There Any Benefit of Drain Placement on Postoperative Complications in Patients Undergoing the Sistrunk Procedure?

Introduction Same-day, outpatient Sistrunk procedure is commonly performed to manage thyroglossal duct cyst anomalies and may lead to postoperative complications. Surgical drains are placed to prevent complications, but recent observations show no advantage and rather increased health care costs and patient discomfort. Objective The study evaluated if drain placement in the Sistrunk procedure offers any benefit on postoperative complications. Methods A retrospective analysis of patient records having undergone same-day, outpatient Sistrunk procedure from 2004 to 2014 was done. Of 58 (38 male and 20 female) patients included, 38 did not have drains placed and the remaining 20 had drains placed. Mean and median age of patients was 18.1 and 13.5 years, respectively. Postoperative complications of patients with drains versus those without drains were statistically analyzed. Results Overall, about 10% of patients had hematoma/seroma (H-S), with 6.9% of patients needing aspiration for H-S; 3.4% had wound infections; and 1.7% had pus formation. No statistically significant differences in Sistrunk-related complications between patient groups (with drain or without drain) were seen using Fisher exact (two-sided) test: H-S (p = 0.08); need for aspiration (p = 0.29); wound infection (p > 0.05); and pus formation (p = 0.35). Chi-square test also did not show any significant difference in the groups in terms of number of follow-ups. Conclusion Surgical placement of a drain in the Sistrunk procedure does not seem to offer any advantage in terms of reducing common postoperative complications. Same-day Sistrunk procedure without any drain placement may be a safer alternative without necessitating hospitalization. More studies with larger sample size are needed for further substantiation.

Regulation of the tumor suppressor PTEN through exosomes: a diagnostic potential for prostate cancer.

PTEN is a potent tumor-suppressor protein. Aggressive and metastatic prostate cancer (PC) is associated with a reduction or loss of PTEN expression. PTEN reduction often occurs without gene mutations, and its downregulation is not fully understood. Herein, we show that PTEN is incorporated in the cargo of exosomes derived from cancer cells. PTEN is not detected in exosomes derived from normal, noncancerous cells. We found that PTEN can be transferred to other cells through exosomes. In cells that have a reduction or complete loss of PTEN expression, the transferred PTEN is competent to confer tumor-suppression activity to acceptor cells. In PC patients, we show that PTEN is incorporated in the cargo of exosomes that circulate in their blood. Interestingly, normal subjects have no PTEN expression in their blood exosomes. Further, we found that the prostate-specific antigen (PSA) is incorporated in PC patients' and normal subjects' blood exosomes. These data suggest that exosomal PTEN can compensate for PTEN loss in PTEN deficient cells, and may have diagnostic value for prostate cancer.