Collision Tumour of Combined Neuroendocrine and Squamous Cell Carcinoma of Nasal Cavity and Paranasal Sinus- Case Report and Review of Literature.

Background: There have been many disputes about the definition, diagnosis, therapy, and prognosis of collision tumours. Case Summary: We describe a rare patient with a collision tumour consisting of high-grade neuroendocrine carcinoma (NEC) and squamous cell carcinoma (SCC) in the right nasal cavity and paranasal sinus. She received surgery, concurrent chemoradiotherapy, and then two cycles of palliative chemotherapy. Follow-up at 26 months after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis. A literature review of previous 27 cases diagnosed with collision tumour of NEC and SCC in the head and neck was also undertaken. Conclusion: It is highly challenging to manage collision tumours because these are two morphologically and etiologically distinct tumours. Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.

Fever and flagellate dermatosis in an otherwise healthy woman.

We report a rare presentation of adult-onset Still disease (AoSD) with flagellate dermatosis and unknown trigger. Atypical skin findings have been increasingly reported for AoSD and may be associated with worse prognosis and systemic complications. Increased awareness of nonclassic skin findings in AoSD may lead to earlier diagnosis and treatment.

Oncological benefits of postoperative radiotherapy in node-negative early stage cancer of the oral cavity with isolated perineural invasion.

Perineural invasion has been widely regarded as a poor prognostic factor in cancer of the oral cavity, but adjuvant treatment based only on this is still debatable. We have made an effort to address the question in a retrospective analysis of data from 2009-15 of patients with early node-negative cancers of the oral cavity. Patients with perineural invasion were divided into those who were treated with radiotherapy and those who were not. The records of a total of 169 patients were analysed, and 118 were given adjuvant radiotherapy and 51 were not. The median (range) duration of follow up was 45 (26-86) months. Of 169 patients, 47 (28%) developed recurrence, 28 in the treated, and 19 in the untreated, group. There was a significant disease-free survival benefit for adjuvant treatment (p = 0.047) but no overall survival benefit (p = 0.54). We conclude that adjuvant radiotherapy should be considered for patients with perineural invasion, even in early cancers of the oral cavity.

Extracapsular extension in oral cavity cancers-predictive factors and impact on recurrence pattern and survival.

Extracapsular extension (ECE) has long been considered a poor prognostic factor in oral cavity cancer, the presence of which warrants intensification of adjuvant therapy. This study was done to analyze the survival of patients with ECE who received adjuvant chemoradiation. Patients with pathologically confirmed squamous cell carcinoma of the oral cavity, with a minimum of 2 years of follow-up, who were treated at a tertiary cancer centre in New Delhi, India during the years 2009-2017, were included. On multivariate analysis, ECE was significantly associated with depth of invasion >10 mm and tumour deposit size >5 mm. Among the node-positive group, patients without ECE had a 5-year disease-free survival (DFS) and 5-year overall survival (OS) advantage over ECE-positive patients of 7.8% (63.8% vs. 56.0%) and 16.5% (87.2% vs. 70.7%), respectively. For patients with ECE, the hazard ratio for DFS and OS was 1.3 (95% confidence interval 0.97-1.75, P = 0.078) and 2.30 (95% confidence interval 1.35-3.92, P = 0.002), respectively. ECE remains one of the strongest predictors of recurrence and survival in oral cancer patients, and despite aggressive adjuvant therapy, distant recurrence is still significantly high.

Pityriasis rubra pilaris-like erythroderma secondary to phosphoinositide 3-kinase inhibition.

BACKGROUND: Phosphoinositide 3-kinase (PI3K) inhibitors are a class of small-molecule inhibitors approved for the treatment of certain leukaemias and lymphomas. Their dermatological adverse event profile is poorly described. AIM: To characterize a rare cutaneous adverse event from PI3K inhibitors in order to help dermatologists and oncologists identify and effectively manage such eruptions. METHODS: This was a retrospective analysis of patients receiving PI3K inhibitors referred to the Skin Toxicities Program in The Center for Cutaneous Oncology. RESULTS: Three patients on PI3K inhibitors for treatment of malignancy developed diffuse erythroderma and keratoderma. Clinical and histopathological findings were consistent with pityriasis rubra pilaris (PRP)-like reactions. All patients improved with topical and oral corticosteroids, oral acitretin, and drug discontinuation. CONCLUSIONS: PRP-like cutaneous eruptions may develop secondary to PI3K inhibition. Early dermatological evaluation of cutaneous toxicities to PI3K inhibitors as well as rapid initiation of disease-specific treatments may help keep patients on life-prolonging anti-cancer therapies.

A gland of diverse pathology and unpredictable behaviour: our experience of primary submandibular gland malignancies.

Submandibular gland tumours are relatively uncommon tumours and demonstrate diverse histological types and a variable prognosis. The aim of this study was to analyze our experience with submandibular malignancies over a period of 6 years (January 2009 to December 2015). Patient data from the 6-year period were reviewed retrospectively and 51 patients with submandibular malignancies were identified. Demographic data, clinicopathological details, treatment received, complications, and follow-up were recorded. The mean age of the 51 patients at presentation was 49.1 years. They were followed up for a mean 20.3 months. Nine of 47 patients (19.1%) developed distant metastasis during follow-up, while only three (6.4%) developed local recurrence. Disease-free survival at 2 years was 69.7% and overall survival at the end of 2 years was 77.8%. Actuarial 5-year survival was 57.8% when all subtypes were considered. The overall mean time to recurrence was 10 months (6-24 months). Nodal positivity was the only prognostic factor that was significant on multivariate analysis, while age, sex, perineural invasion, and grade were not. With advances in surgical and radiotherapy techniques, loco-regional control rates have improved greatly; however, effective adjuvant treatment to prevent systemic relapse is still lacking.

Prognostic Factors in Indian Patients Operated for Soft Tissue Sarcomas-a Retrospective Cross-sectional Analysis.

Soft tissue sarcomas are a rare entity. While surgery is established as the mainstay of treatment, the exact role and sequencing of adjuvant therapy is not well defined. Literature on Indian patients with soft tissue sarcoma with respect to clinical profile and prognostic factors is scarce. We retrospectively analysed the data of 112 patients operated for soft tissue sarcoma of extremity or trunk (excluding retroperitoneal and mediastinal sarcomas, round cell histology) at our institute from 1 January 2009 to 31 December 2013. Around half the patients were less than 50 years of age and around a third had size more than 10 cm. Oncological outcome was correlated with various demographic, tumour-related and treatment-related factors using SPSS 22. Overall survival at 5 years was 73.2 % and event-free survival at 5 years was 42.2 %. At final follow-up (mean of 44.85 ± 4.64 months), local recurrence was seen in 31.9 % and distant metastasis was seen in 30.1 % of the patients. Using both univariate and multivariate analysis, younger age (<50 years), larger size (>10 cm, but not >5 cm) and pathologically positive lymph nodes were the only factors found significantly affecting overall survival. The clinical profile and prognosis of Indian patients with soft tissue sarcoma were found to be different from that reported in Western literature. The impact of established prognostic indicators for soft tissue sarcoma also differed in Indian patients, which may have both prognostic and therapeutic implications.

Impact on Radiological and Pathological Response with Neoadjuvant Chemoradiation and Its Effect on Survival in Squamous Cell Carcinoma of Thoracic Esophagus.

BACKGROUND: Neoadjuvant chemoradiation (NCRT) has been shown to improve survival in patients with locally advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the role of 18-FDG PET-CT in predicting pathological response to NCRT. MATERIAL AND METHODS: We assessed 70 patients of esophageal SCC who underwent NCRT and were evaluated with baseline and post chemoradiation 18F-FDG PET-CT scan. Receiver operating characteristic (ROC) curve was generated by analyzing the sensitivity and specificity of different cut-off points for defining a positive test and their ability to predict pathological complete response. Univariate and multivariate analysis were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Radiological and pathological complete response was achieved in 44.3 % (n = 31) and 34.3 % (n = 24) patients, respectively. Using ROC curves, post-treatment standardized uptake value (SUV) max [3.25, area under curve (AUC) 0.752] and % change in SUVmax cut-off value (72.32 %, AUC 0.705) was used to predict pathological response. Significant associations between pathological response in primary tumor and post chemotherapy/radiotherapy SUVmax values (p = 0.016), % change in SUVmax (p = 0.006), radiological response in primary (p = 0.006), and grade of dysphagia at presentation (p = 0.041) were observed. Mean overall survival and relapse free survival was 83 and 58 %, respectively at 34 months. CONCLUSION: 18F-FDG PET-CT can be used to predict pathological response to NCRT in locally advanced SCC.

Preservation of Aesthetics of Breast in Pectoralis Major Myocutaneous Flap Donor Site in Females.

BACKGROUND AND OBJECTIVES: In females, raising a pectoralis major myocutaneous flap is challenging and primary closure of flap donor site causes breast deformity with medial displacement of nipple areola complex. To avoid this distortion, a new method of donor site closure is devised. METHODS: A parasternal skin paddle which has better vascularity is planned while doing a pectoralis major myocutaneous flap in females and a lateral flap planned along the lateral breast curve is used to cover the donor site. The lateral flap donor site is primarily closed. This prevents medial displacement of nipple areola complex. RESULTS: A total of 47 patients underwent donor site flap closure technique. Minor complications in form of marginal necrosis near the tip of the flap were observed in 10.6 % patients. The donor breast of all these PMMC flaps had good contour and aesthetic positioning of nipple areola complex. CONCLUSION: Donor site morbidity with respect to breast distortion has not been studied so far in case of females so our study stands unique in this aspect. Using this technique of planning PMMC in females ensures a skin paddle of better vascularity and restores the breast aesthetics.

Palliative weekly chemotherapy along with cetuximab in recurrent and metastatic head and neck cancers: a retrospective analysis.

BACKGROUND: This study was undertaken to report the results of weekly combination chemotherapy with cetuximab in recurrent/metastatic head and neck squamous cell carcinoma (R/M SCCHN). MATERIALS AND METHODS: Retrospective analysis of 35 R/M SCCHN patients who received cetuximab with weekly paclitaxel and platin (cisplatin/carboplatin) from SCCHN August 2006 to October 2008 at our Institute was performed. RESULTS: Thirty-five patients (33 [94.3%] males and 2 [5.7%] females) received the planned weekly chemotherapy protocol. Median age of these patients was 52 years. Of the SCCHN 32 evaluable patients, 25 patients showed symptomatic improvement and 7 showed no improvement. Radiological responses using RECIST criteria reported CR in 1 patient (3.1%), PR in 17 patients (53.1%), and SD in 6 patients (18.8%). The remaining six patients demonstrated disease progression while two could not be assessed. Median overall survival (OS) was 8.016 months (95% CI; 6.572--9.461) and median PFS was 5.782 months (95% CI; 4.521--7.044). The major chemotherapy-related grades 2 and 3 toxicity recorded was cetuximab-induced rash reported in 24 patients. No treatment-related death within 30 days was observed. CONCLUSION: Cetuximab with weekly combination chemotherapy (Paclitaxel + Platinum compound) has shown promise, demonstrating comparable response and outcomes with acceptable toxicity in R/M SCCHN patients.

Arginine vasotocin neuronal phenotypes among congeneric territorial and shoaling reef butterflyfishes: species, sex and reproductive season comparisons.

Arginine vasotocin (AVT) and the homologous arginine vasopressin (AVP) neuropeptides are involved in the control of aggression, spacing behaviour and mating systems in vertebrates, but the function of AVT in the regulation of social behaviour among closely-related fish species needs further clarification. We used immunocytochemical techniques to test whether AVT neurones show species, sex or seasonal differences in two sympatric butterflyfish sister species: the territorial monogamous multiband butterflyfish, Chaetodon multicinctus, and the shoaling polygamous milletseed butterflyfish, Chaetodon miliaris. The territorial species had larger AVT-immunoreactive (-ir) somata within the preoptic area, and higher AVT fibre densities within but not limited to the ventral telencephalon, medial and dorsal nucleus of the dorsal telencephalon, torus semicircularis, and tectum compared to the shoaling nonterritorial species. Furthermore, AVT-ir somata size and number did not differ among sexes or spawning periods in the territorial species, and showed only limited variation within the shoaling species. The distinct difference in AVT neuronal characteristics among species is likely to be independent of body size differences, and the lack of sex and seasonal variability is consistent with their divergent but stable social and mating systems. These phenotypic differences among species may be related to the influence of AVT on social spacing, aggression or monogamy, as reported for other fish, avian and mammalian models. The present study provides the first evidence for variation in vasotocin neural organisation in two congeneric and sympatric fish species with different social systems.

Favourable impact of intensity-modulated radiation therapy on chronic dysphagia in patients with head and neck cancer.

The aim of this study was to evaluate the impact of intensity-modulated radiation therapy (IMRT) on the incidence and severity of chronic dysphagia in patients with head and neck cancer. 62 evaluable patients with head and neck cancer who were treated with IMRT with or without concurrent chemotherapy were analysed. The majority of the patients (77.4%) had advanced locoregional disease. 45 patients underwent definitive IMRT and 17 received post-operative IMRT. Concurrent chemotherapy was given to 29 of the 45 patients treated with definitive IMRT. The average prescribed dose to clinical target volume (CTV)1 was 66-70 Gy (definitive IMRT) and 56-62 Gy (post-operative IMRT); 60 Gy to CTV2; 54 Gy to CTV3; and 50-52 Gy to the supraclavicular area. At a median follow-up of 19 months, 2-year actuarial locoregional control and survival was 77% and 74%, respectively. At 6 months after IMRT, chronic dysphagia was Grade 0 in 77.1% of patients, Grade 1 in 10.5% and Grade 2 in 12.3%. Acute mucositis showed no correlation with long-term dysphagia. The percutaneous endoscopic gastrostomy or nasogastric tube was removed in all of the patients within 8 weeks of completion of treatment. Xerostomia was Grade 0 in 61.4% of patients, Grade 1 in 31.5% and Grade 2 in 7% of patients. In conclusion, IMRT conferred a major favourable impact on chronic dysphagia in patients with locally advanced head and neck cancers, with satisfactory locoregional control.

Redefinition of dystrophin isoform distribution in mouse tissue by RT-PCR implies role in nonmuscle manifestations of duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is caused by a defect in a 427-kDa membrane-associated protein: dystrophin. The DMD gene also encodes several shorter isoforms which are believed to participate in nonmuscle manifestations of DMD, including abnormal retinal electrophysiology, dilated cardiomyopathy, mental retardation, and hearing defects. The purpose of this work was to determine the normal tissue expression of full-length dystrophin (Dp427) and the dystrophin isoforms Dp260, Dp140, Dp116, and Dp71, to aid in understanding what roles these isoforms might play in DMD nonmuscle manifestations. RT-PCR was performed on mRNA isolated from wild-type C57BL/6J mouse tissues, including brain, cardiac muscle, eye, intestine, kidney, liver, lung, skeletal muscle, spleen, stomach, testis, thymus, and uterus. RT-PCR amplification demonstrated that the isoforms were in a number of tissues which had not been revealed by previous Western and Northern blot analyses. Dp427 was expressed at equal levels in all tissues. Dp260 and Dp140 were present in all tissues tested, but the levels of expression varied. Dp116 was expressed in a subset of tissues and levels of expression varied. Dp71 was constitutively expressed in all tissues, suggesting that this isoform plays a basic role in normal tissue function. The expanded tissue distribution supports the hypothesis that dystrophin isoforms serve essential and unique functions, necessitating further investigation into their potential roles in DMD nonmuscle manifestations.

Role of steroid hormone and growth factor receptors and proto-oncogenes in the behavior of human mammary epithelial cancer cells in vitro.

The cultivation of cells from primary breast cancers is very unpredictable. The majority of breast-cancer-derived cell lines are of metastatic origin. To define the characteristics of tumor cells which govern their ability to grow in vitro as primary cultures as well as continuous or established culture cell lineages, human mammary epithelial cancer (HMEC) cells from 18 cases of unselected primary breast cancer were propagated in culture. Propagation of HMEC cells in vitro as monolayers in primary culture was successful in 10 out of 18 (55.5%) cases, which showed continous proliferation of tumor cells only up to 6-8 passages before they reached senescence. An investigation of the effects of phenotypic expression of estrogen receptors (ER), the progesterone receptors, c-erbB-2 oncoprotein and epidermal growth factor receptors (EGFR) on the capacity of HMEC cells to grow in vitro as monolayers showed that expression of ER and EGFR is required for controlling tumor proliferative activity in vitro. Expression of ER protein made the growth of HMEC cells more difficult, while expression of EGFR protein made their growth in vitro easier. Phenotypic characteristics of floating HMEC cells were found to be different from those grown on cover slips as adherent cultures, suggesting a selective growth of HMEC cells of a specific phenotype in culture. Cultured HMEC cells in subsequent passages showed a decrease in their proliferative capacity, alterations in phenotypic characteristics and development of morphologic features of terminal differentiation, resulting in senescence.

Transverse colon conduit urinary diversion in patients treated with very high dose pelvic irradiation.

OBJECTIVE: To study the results of transverse colon conduit urinary diversion in patients receiving very high dose pelvic irradiation (> or = 65 Gy). PATIENTS AND METHODS: Records were reviewed for 30 such patients who underwent transverse colon conduit as a primary form of urinary diversion between January 1986 and June 1992. Most of the conduits were constructed using refluxing ureterocolic anastomoses with stents. RESULTS: There was no operative mortality. Although the procedure was associated with a complication rate of 37% and a re-operation rate of 20%, there were no bowel or urinary anastomotic leaks. The operation could be safely performed on patients with renal failure, with 83% of such patients showing normal or improved serum creatinine levels post-operatively. CONCLUSION: The advantages of transverse colon conduit urinary diversion are the use of non-irradiated bowel and ureters for diversion. We recommend it as a primary form of urinary diversion in these high risk cases.

Intravesical formalin for hemorrhagic cystitis following irradiation of cancer of the cervix.

OBJECTIVE: To determine the effectiveness of intravesical formalin instillation in hemorrhagic cystitis following irradiation of cancer of the cervix. METHOD: Records were reviewed for 35 patients with hemorrhagic radiation cystitis who underwent treatment with 1% (n = 22), 2% (n = 10), and 4% formalin (n = 4), using Fair's technique. RESULT: Complete response was seen in 31 patients (89%) and partial response in 3 patients (8%) after a single instillation. Minor complications were seen in 19 patients (54%). Major complications occurred in 11 patients (31%), with 5 cases requiring subsequent urinary diversion. One patient died of persistent bleeding and probable formalin toxicity. Hematuria recurred in 7 patients achieving complete response at a mean period of 8 months after treatment. A 1% solution was as effective in controlling hematuria as higher concentrations and was associated with significantly less morbidity. CONCLUSION: Intravesical instillation of 1% formalin is an effective treatment for intractable hematuria secondary to radiation cystitis.