Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.

OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

HER 2/neu Overexpression in Oral Squamous Cell Carcinoma and Its Clinico-Pathological Association at a Tertiary Care Center in Eastern India.

Human epidermal growth factor receptor 2/neu (HER2/neu) is known to serve as a prognostic and predictive biomarker in several cancers such as breast, gastric and ovarian cancers. In head and neck squamous cell carcinoma, HER2/neu expression is seen but in a fluctuated manner. Hence, its role as a prognostic factor in oral squamous cell carcinoma (OSCC) needs evaluation. To determine the HER 2/neu overexpression in OSCC patients and its association with clinical and pathological parameters. 74 patients of OSCC treated between 2016 and 2018 were included in the study. Immunohistochemistry was done on tissue samples from these patients and HER2/neu expression was measured. Both biopsy and resected specimens were considered for the study. Out of 74 patients, 47.3% (35) were operated and 52.7% (39) were not operated due to loss to follow-up. No significant association was found (p = 0.636, OR = 0.68, CI = 0.14-3.34) between lymphovascular invasion (LVI) and HER2/neu expression. Similar results were seen for perineural invasion (PNI) (p = 0.490, OR = 0.53, CI = 0.88-3.24), depth of invasion (p = 0.21), grade of tumor (p = 0.214), clinical-stage (p = 0.511) and pathological stage (p = 0.091). No significant association existed between HER2/neu expression and LVI, PNI, clinical-stage, the grade of tumor and the pathological stage of oral squamous cell carcinoma.

Metastatic hobnail variant of papillary thyroid carcinoma: A diagnostic challenge in cell block preparation.

Hobnail variant of papillary thyroid carcinoma (HV-PTC) is an unusual entity recently included in WHO classification of endocrine tumors (2017) and proposed as an aggressive variant of PTC. Compared to patients of classical counterparts, HV-PTC frequently has extrathyroidal extension, exhibits nodal or distant metastasis, and responds poorly to radioiodine treatment, leading to increased mortality. We hereby describe the cytohistological and immunohistochemical features of a metastatic HV-PTC in 55-year-old male, previously diagnosed as poorly differentiated papillary thyroid carcinoma in thyroidectomy specimen. Five years after total thyroidectomy with radical neck dissection the patient presented with gross pleural effusion showing multiple lung parenchymal and pleural based lesions with complete collapse of lung on computed tomography scan. The conventional cytology of pleural fluid showed dyscohesive cells arranged in micropapillary form gave the suggestion of metastatic papillary carcinoma. But the cell block preparation highlighted >30% hobnail cells arranged in micropapillary pattern showing increased atypical mitosis and occasional pseudoinclusions. Supplemented with immunohistochemistry (CK19, TTF-1, and p53), final diagnosis HV-PTC was made.

Histopathological and Immunohistochemical Evaluation of CDX2 and Ki67 in Colorectal Lesions with their Expression Pattern in Different Histologic Variants, Grade, and Stage of Colorectal Carcinomas.

BACKGROUND: A variety of colorectal lesions are surgically treated encompassing both benign and malignant polyps and colorectal cancer (CRC). CRC is the third most common cause of death in developed countries. Over the last decade, CDX2 has been linked to CRC progression, with reduced expression of the protein associated with more advanced tumor stage, vessel invasion, and metastasis. AIMS AND OBJECTIVES: To analyze the histopathology and immunohistochemistry (IHC) of CDX2 and Ki67 with their expression pattern; in different lesions of colon and rectum with special reference to various grade/stage/histological variants of CRC and to find out whether they can be used as possible predictive marker. MATERIALS AND METHODS: The study conducted was hospital based, both retrospective and perspective type comprising colorectal samples of total 367 cases (N) within a period of 2½ years. Surgical samples were collected, then grossed, processed, stained with routine hematoxylin and eosin stain in our department followed by IHC of CDX2 and Ki67 in only 60 randomly selected cases (n = 60). RESULTS: Out of total 367 cases, 265 cases were prospective study and 102 cases were retrospective study (240 cases were colonic lesions, and 127 are rectal lesions). The samples included were both from colonoscopy biopsy (small) 319 cases and 48 colectomy specimen (large). Mean age of the study participants was 49.62 years with a standard deviation of 17.34 years and predominantly male, but the difference was not statistically significant (P > 0.05). Colon (238 cases, 64.9%) as a whole affected more than rectum and left sided tumors more than the right side. All 60 cases were found to be positive for CDX2 expression (i.e., 100%); majority (n = 38) being carcinoma cases possessing high score and was statistically significant (P = 0.008, using Chi-square test) indicating strong association, whereas Ki-67 showed an increased index from noneoplastic to neoplastic cases. CONCLUSION: These markers can be used as future predictive biomarkers which will precisely evaluate risk group, prognosis, and response to therapy hence can be used as target therapy reducing irrational treatment.