Study of tumor transglutaminase 2 expression in gallbladder cancer - Is it a novel predictor of survival?

BACKGROUNDS/AIMS: Transglutaminase 2 (TG2) is known to be an important mediator of inflammation induced carcinogenesis pathway. Chronic inflammation is the most important causative factor in Gallbladder cancer (GBC) carcinogenesis. We analyzed the expression of TG2 in GBC and its role as potential prognostic marker, first of its kind study. METHODS: We analyzed TG2 expression in 100 cases of GBC and 28 cases of non-cancer gallbladder specimen (calculus cholecystitis). We studied TG2 expression in GBC in comparison to control group and evaluated its role as a potential prognostic marker. RESULTS: TG2 score (1-9) was calculated by multiplying percentage cytoplasmic expression (P) with intensity of expression (I) in tumor cells. Positive TG-2 expression was observed in 62% of GBC patients compared to only 21% (n=6) in control group (p=0.001). In curative resection subgroup (n=54), TG2 positive patients showed shorter disease free survival rate (p=0.04) and higher rate of recurrence (p=0.03) compared to TG2 negative patients. TG2 positive expression was observed in 15/16 of patients with recurrent disease. In palliative treatment subgroup, patients with strong TG2 positive expression had poorer disease specific survival (p=0.01) as compared to weakly positive group. On multivariate analysis, lymph node status (p=0.03) and TG2 expression (p=0.037), were found to be significant predictor of recurrence and eventual survival. CONCLUSIONS: Positive TG2 expression was related to higher recurrence rates post curative surgery, shorter disease free and overall survival and ultimately portended poor prognosis. It may be helpful in better prognostication and tailoring therapeutic approach for better management of GBC.

Validation of the Brandwein Gensler Risk Model in Patients of Oral Cavity Squamous Cell Carcinoma in North India.

India has one of the highest incidences of oral squamous cell carcinoma (OSCC), with 75,000-80,000 new cases a year. The outcome in early oral cancer is better, but a significant proportion (12-14%) of these patients still relapses and dies due to locoregional or distant recurrences. Several clinicopathological and molecular factors have been used to prognosticate and predict outcomes in these patients of OSCC. The present study aims to validate Brandwein Gensler (BG) risk predictive model in surgically treated OSCC patients in a tertiary care centre in North India. All oral cavity cancer patients, treated in the Department of Surgical Oncology, King George's Medical University, between 2013 and 2017, were reviewed. Patients with histologically diagnosed OSCC, aged > 18 years undergoing primary surgical resection were included in the study. The final histopathological evaluation was done by a dedicated pathologist to categorize patients according to BG model risk categories. This model comprises of three factors, lymphocytic host response, perineural invasion and worst pattern of invasion, scored by the method described by Brandwein Gensler et al. The sum of these scores is used to define low, moderate and high risk categories. The study, conducted during 2013-2017, included 149 patients. Median age was 45 years (range 25-75 years). Tobacco use was noted in 143 patients. Buccal mucosa was the most common site (51%). Surgical margins were clear (> 5 mm) in 97.9% cases. Postoperative radiotherapy was given in 47.7% patients. Locoregional recurrences (LRR) (primary site and neck) were documented in 17 of the 149 patients (11.4%). There was no synchronous or metachronous distant metastasis noted in any of the study patients. Six patients had disease specific mortality. Among the 17 patients with LRR, majority (11) belonged to the high risk category of the BG risk model. Adjuvant radiotherapy had been administered in 10 of these 11 recurrent patients belonging to the high risk category. The Brandwein Gensler risk model is predictive of locoregional recurrences (p = 0.02) for OSCC undergoing primary surgery. It can be used to devise strategies to prevent recurrences or identification of recurrences at an earlier point for salvage. The benefit of further escalation of adjuvant therapy in the high risk category needs further studies, as 90% patients in this group recurred despite complete adjuvant treatment.

Role of serum HE4 as a prognostic marker in carcinoma of the ovary.

BACKGROUND: Epithelial ovarian cancer is the second most common gynecological cancer. Human Epididymis Protein 4 is a novel biomarker for ovarian cancer. This study aims to explore the role of HE4 in monitoring recurrence and prognostication of ovarian cancer by predicting overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In total, 149 patients with ovarian carcinoma were enrolled in the study. Baseline and post-treatment 3 monthly biomarker levels were recorded. For analysis, patients were divided into primary debulking surgery (PDS) and interval debulking surgery (IDS) groups. Statistical analysis was done using SPSS 24. RESULTS: Median age of patients at diagnosis was 45 (19-75) years. Recurrence was seen in 68.5% (n = 102) patients. The sensitivity of serum HE4 in detecting recurrence was 85.3% (95%CI: 76.95%-91.5%) and specificity was 91.5% (95%CI: 89.5%-98.2%). A >80% decline in HE4 levels during treatment indicated a better PFS, which was statistically significant in both groups (P = 0.04 in PDS and P = <0.001 in IDS group). Multivariate analysis suggested that OS was influenced by optimal cytoreduction in both groups of patients and stage in the IDS group. On the contrary, PFS was influenced by stage and response in HE4 levels in both groups. CONCLUSION: HE4 levels have similar sensitivity but more specificity when compared with CA125 in diagnosing recurrent ovarian cancer. A >80% decline in HE4 levels during treatment predicts better PFS and can help in prognostication.

Germ Cell Tumor Ovary: an Institutional Experience of Treatment and Survival Outcomes.

Malignant germ cell tumors (GCT) of the ovary account for 2-3% of all ovarian neoplasms and occur mostly in the second and third decade of life. Over the past three decades, survival rates for germ cell tumors have dramatically improved, coincident with more aggressive surgical staging and combination chemotherapy. Although there are several studies describing ovarian GCT and fertility-preserving surgery in the western population, there is very little Indian data. We present our experience of germ cell tumor ovary in the Department of Surgical Oncology, King George's Medical University over the last 5 years with special emphasis on treatment outcome and role of fertility preservation surgery. A retrospective review of medical records of patients with ovarian germ cell tumors, treated at our center from January 2012 to December 2016, was performed. Epidemiological and clinical profile of patients was reviewed. Clinical stage of presentation, neoadjuvant treatment, surgical treatment, and adjuvant treatment data were analyzed, and treatment outcome data was recorded. Patient follow-up was done to ascertain disease-free interval, treatment outcome, ability to conceive following fertility-preserving surgery, and quality of life. A total of 39 patients with ovarian germ cell tumor were treated during this period. Their median age at diagnosis was 22 years (range 11-65 years) and most common mode of presentation was abdominal lump without ascites. Around 36.8% (n = 14) patients had conservative surgery with preservation of opposite ovary and uterus. Most patients (71.1% n = 27) received neoadjuvant chemotherapy due to advanced disease in form of ascites or large mass, and five of these patients were amenable to fertility-preserving surgery after chemotherapy. Nine out of the fourteen patients have had return of menstrual function after a mean period of 3.5 + 0.5 months. One patient who underwent fertility-preserving surgery has delivered healthy children after treatment. Stage distribution for stage I to IV was as follows: 15.4% (n = 6), 35.9% (n = 14), 46.2% (n = 18), and 2.6% (n = 1), respectively. Dysgerminoma was the commonest histology (37.1% n = 13) followed by teratoma (22.9% n = 8). 17.1% (n = 6) patients had recurrence, with a median time to recurrence 16 months (range 5.5 to 37 months) and they were treated with second-line chemotherapy. Germ cell tumor of the ovary is an eminently treatable disease and selected patients can be managed with fertility-preserving surgery. BEP is the most effective chemotherapy regimen. Disease-free survival rates in these patients are quite high and recurrences can be managed with second-line chemotherapy.

Development of a New Outcome Prediction Model in Early-stage Squamous Cell Carcinoma of the Oral Cavity Based on Histopathologic Parameters With Multivariate Analysis: The Aditi-Nuzhat Lymph-node Prediction Score (ANLPS) System.

The aim of this study was to evaluate the histopathologic parameters that predict lymph node metastasis in patients with oral squamous cell carcinoma (OSCC) and to design a new assessment score on the basis of these parameters that could ultimately allow for changes in treatment decisions or aid clinicians in deciding whether there is a need for close follow-up or to perform early lymph node dissection. Histopathologic parameters of 336 cases of OSCC with stage cT1/T2 N0M0 disease were analyzed. The location of the tumor and the type of surgery used for the management of the tumor were recorded for all patients. The parameters, including T stage, grading of tumor, tumor budding, tumor thickness, depth of invasion, shape of tumor nest, lymphoid response at tumor-host interface and pattern of invasion, eosinophilic reaction, foreign-body giant cell reaction, lymphovascular invasion, and perineural invasion, were examined. Ninety-two patients had metastasis in lymph nodes. On univariate and multivariate analysis, independent variables for predicting lymph node metastasis in descending order were depth of invasion (P=0.003), pattern of invasion (P=0.007), perineural invasion (P=0.014), grade (P=0.028), lymphovascular invasion (P=0.038), lymphoid response (P=0.037), and tumor budding (P=0.039). We designed a scoring system on the basis of these statistical results and tested it. Cases with scores ranging from 7 to 11, 12 to 16, and ≥17 points showed LN metastasis in 6.4%, 22.8%, and 77.1% of cases, respectively. The difference between these 3 groups in relation to nodal metastasis was very significant (P<0.0001). A patient at low risk for lymph node metastasis (score, 7 to 11) had a 5-year survival of 93%, moderate-risk patients (score, 12 to 16) had a 5-year survival of 67%, and high-risk patients (score, 17 to 21) had a 5-year survival of 39%. The risk of lymph node metastasis in OSCC is influenced by many histologic parameters that are not routinely analyzed in pathologic reports. These significant independent factors were graded to design a scoring system that permits accurate evaluation of the risk of metastasis with accuracy independent of the traditional TNM system or isolated histologic parameters. The need for neck node dissection can be predicted depending upon the scores obtained.

Tuberculous osteomyelitis of sternum secondary to primary tuberculous mastitis.

Sternal tuberculosis secondary to tuberculous mastitis is uncommon. The invasion of the sternum following a primary focus in the breast has not been reported. This may be due to the resistance offered by pectoral fascia and periosteum to the spread of infection into the bone. We present a case of tubercular sternal osteomtyelitis following tubercular mastitis in a 40-year old female. A brief case report and a review of literature are presented.