Pattern of Post-Operative Infections Among Oral Cavity Cancer Patients in a Tertiary Care Cancer Centre: A Prospective Study.

Surgical site infections (SSIs) constitute a major problem among patients who undergo surgery for oral cancer and remain a substantial cause of morbidity, prolonged hospitalization and death. The aim of this study was to assess the microbial spectrum of post-operative wound infections and to assess the outcome of appropriate antibiotic usage in patients who underwent surgery for oral cancer. This was a prospective observational study done in a tertiary care cancer hospital. Patients who underwent surgery for cancers of the oral cavity during the period January 2014 to December 2016 were included in the study. The spectrum of infections, risk factors, microbial profile, antibiotic susceptibility pattern, treatment given and outcome were assessed. A total of 1431 patients who underwent surgery for cancers of the oral cavity during the study period were followed up. SSIs were noticed in 118 (8%) post-operative cases. This included 55 (76.4%) incisional SSIs and 17 (23.6%) organ/space SSIs. Culture of the surgical site in 72 infected patients yielded a total of 122 isolates. Thirty patients (41.6%) had polymicrobial infections. Gram-negative bacterial isolates (70.5%) outnumbered gram-positive bacterial isolates (27%). Majority of the patients (48 patients-66.6%) were in stage IV disease. Successful management of patients with bacterial infections depends on early identification of bacterial pathogens and selection of an effective antibiotic against the organism. Judicial use of antibiotics is also very essential to prevent the development of drug resistance.

ß-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells.

Recent advancements in cancer research have shown that cancer stem cell (CSC) niche is a crucial factor modulating tumor progression and treatment outcomes. It sustains CSCs by orchestrated regulation of several cytokines, growth factors, and signaling pathways. Although the features defining adult stem cell niches are well-explored, the CSC niche is poorly characterized. Since membrane trafficking proteins have been shown to be essential for the localization of critical proteins supporting CSCs, we investigated the role of TUBB4B, a probable membrane trafficking protein that was found to be overexpressed in the membranes of stem cell enriched cultures, in sustaining CSCs in oral cancer. Here, we show that the knockdown of TUBB4B downregulates the expression of pluripotency markers, depletes ALDH1A1+ population, decreases in vitro sphere formation, and diminishes the tumor initiation potential in vivo. As TUBB4B is not known to have any role in transcriptional regulation nor cell signaling, we suspected that its membrane trafficking function plays a role in constituting a CSC niche. The pattern of its expression in tissue sections, forming a gradient in and around the CSCs, reinforced the notion. Later, we explored its possible cooperation with a signaling protein, Ephrin-B1, the abrogation of which reduces the self-renewal of oral cancer stem cells. Expression and survival analyses based on the TCGA dataset of head and neck squamous cell carcinoma (HNSCC) samples indicated that the functional cooperation of TUBB4 and EFNB1 results in a poor prognosis. We also show that TUBB4B and Ephrin-B1 cohabit in the CSC niche. Moreover, depletion of TUBB4B downregulates the membrane expression of Ephrin-B1 and reduces the CSC population. Our results imply that the dynamics of TUBB4B is decisive for the surface localization of proteins, like Ephrin-B1, that sustain CSCs by their concerted signaling.

A novel reporter construct for screening small molecule inhibitors that specifically target self-renewing cancer cells.

Cancer stem cells (CSCs) are a subset of cancer cells, which possess self-renewal ability, and lead to tumor progression, metastasis, and resistance to therapy. Live detection and isolation of CSCs are important to understand the biology of CSCs as well as to screen drugs that target them. Even though CSCs are detected using surface markers, there is a lot of inconsistencies for that in a given cancer type. At the same time, self-renewal markers like ALDH1A1, OCT4A and SOX2, which are intracellular molecules, are reliable markers for CSCs in different cancers. In the present study, we generated a reporter construct for self-renewing CSCs, based on ALDH1A1 expression. Oral cancer cells harboring ALDH1A1-DsRed2 were used to screen inhibitors that target CSCs. Our results showed that Comb1, a cocktail of inhibitors for EGF and TGF-ß pathways and their intermediates, effectively reduced the DsRed2 population to 34%. Our immunohistochemical analysis on primary oral cancer corroborated the importance of EGF and TGF-ß pathways in sustaining CSCs. Since these two pathways are also critical for the self-renewal and differentiation of normal stem cells, Comb1 might abolish them as well. On analysis of the effect of Comb1 on normal murine bone marrow cells, there was no significant change in the stem cell self-renewal and differentiation potential in the treated group compared to untreated cells. To conclude, we claim that ALDH1A1-DsRed2 is a useful tool to detect CSCs, and Comb1 is effective in targeting CSCs without affecting normal stem cells.

Retrospective Outcome Analysis of Buccal Mucosal and Lower Alveolar Squamous Cell Carcinoma from a High-Volume Tertiary Cancer Centre.

To evaluate treatment outcome and factors affecting locoregional control and distant metastasis in buccal mucosal and lower alveolar squamous cell carcinoma. A retrospective analysis of all diagnosed cases of buccal mucosal and lower alveolar squamous cell carcinoma in patients who underwent surgical treatment in 2011 was included from the data base. The patients were analysed for their habits, trismus, skin and bone involvement, neck nodes, type of surgery for primary and nodes, differentiation of tumour, pathological nodal status, recurrence site, and duration after completion of treatment and follow-up. A total of 114 patients were included in the study. The mean duration of follow-up was 23.8 months. On follow-up, 30 patients had recurrence (26.32%) either locoregional or distant metastasis. Age less than 45 years, nodal positivity, presence of perineural invasion, extracapsular spread, and degree of differentiation were found to be statistically significant by univariate analysis (p < 0.05). On multivariate analysis, node positivity and presence of perineural invasion emerged as independent predictors of recurrence. Cox regression analysis showed trismus, node positivity, and perineural invasion are significantly associated with recurrence. Aggressive multimodality treatment achieves good local control rates even in locally advanced disease, and the intent of treatment should be curative. Node positivity, presence of perineural invasion, and presence of trismus are found as independent predictors of recurrence. Clinically, presence of trismus is associated with poorer outcomes in view of higher stage.

Prospective Evaluation of Surgical Outcome After Transoral CO2 Laser Resection of Potentially Malignant and Early Oral Malignancy.

A prospective observational study was done at the Regional Cancer Centre, Thiruvananthapuram, a tertiary referral center for cancer care in India with an aim to assess the surgical outcomes of CO2 laser resection of oral lesions in terms of operative time, blood loss, hospital stay, postoperative pain, time to re-epithelization, pathological margins achieved and the postoperative scar. The excision was performed in 30 patients with a diagnosis of either potentially malignant lesions (leucoplakia, erythroplakia) or early cancers, i.e., carcinoma in situ or T1/T2 squamous cell carcinoma of the anterior oral cavity (tongue, buccal mucosa), adhering to standard oncological principles, and the resultant defect was left for secondary healing.

Can Metastatic Lymph node ratio be used as an independent prognostic factor in Carcinoma tongue?

BACKGROUND: Lymph node metastasis is an established prognostic factor in carcinoma of tongue. The association between lymph node ratio (LNR, the ratio of positive lymph nodes to the total number of dissected lymph nodes) and survival has been recently studied. But the available literature is mostly retrospective in nature and they take the broad group of oral squamous cell carcinoma as a whole and not as a single sub-site; also it does not take in to consideration the importance of standardising the minimum number of lymph nodes to be dissected or a single head and neck pathologist examining the specimen to avoid wide variations in the ratio and to reduce the bias. Hence we sought to determine using a prospective study whether the lymph node ratio, as an independent factor impacts survival in node-positive squamous cell carcinoma of tongue and whether a cut-off can be arrived at to risk stratify the patients. METHODS: We prospectively studied 51 consecutive pathologically node positive patients with squamous cell carcinoma tongue who satisfied our selection criteria. A standard surgery for the primary was done under frozen control and a comprehensive neck dissection, with the minimum number of lymph node harvest kept at 15. All the specimens were examined by a single head and neck pathologist. Further adjuvant treatment was given according to our institution protocol. They were followed up with a regular clinical examination for an average period of 24 months. The 2 Yr OS and DFS were calculated using the Kaplan Meier method. LNR was subjected to univariate and multivariate analyses. RESULTS: The 2 yr OS was 37.8% for patients with LNR>0.10 compared with 88.2% for patients with LNR <0.10 (p value=0.0187).Similarly, the DFS was 46.3% for patients with LNR >0.10compared with 83.6% for those with LND<0.10 (p value=0.0859).LNR was a significant prognostic factor in both univariate and multi variate analyses. CONCLUSION: In squamous cell carcinoma of tongue, an increased Lymph node ratio (LNR) is a strong predictor of decreased survival. A lymph node ratio (LNR)>0.10 is associated with a worse outcome.

Risk Factors for Post-operative Complications in Primary Oral Cancer Surgery-a Prospective Study.

The surgical treatment of oral cavity cancers can be influenced by post-operative complications. Identification of risk factors based on clinical characteristics may assist in therapeutic planning and thereby helps in reducing complications. Here, an attempt is made to identify the factors associated with post-operative complications (complications developing within 1 month of surgery) in patients undergoing primary oral cancer surgery. Six hundred seventy-six consecutive patients who underwent primary surgery for oral cancer from December 2007 to May 2010 were prospectively evaluated. The risk factors that predict for post-operative complications were analyzed. There was one mortality and 15% (103 patients) had post-operative complications. The complications included metabolic complications, primary site problems, donor site problems, and systemic complications. Fifteen factors were found statistically significant for the development of post-operative complications by univariate analysis. On multivariate analysis, three of the 15 factors, i.e., presence of COPD, full thickness wide excision, and increased duration of surgery were found to be independently associated with the development of post-operative complications. Presence of COPD, full thickness wide excision, and increased duration of surgery were identified as independent risk factors for post-operative complications in primary oral cancer surgery. The development of complications invariably resulted in increased hospital stay. Hence, the prompt recognition of risk factors for complications based on pre-operative clinical characteristics plus the identification of the risks associated with the surgical procedure can help in determining the appropriate therapeutic planning to prevent complications and in achieving cost effectiveness.

Oncological Safety of Submental Artery Island Flap in Oral Reconstruction - Analysis of 229 Cases.

Submental artery island flap (SMIF) is gaining popularity as a viable alternative to free flaps in carefully selected oral cavity defects after surgical extirpation of cancers.The current paper looks into the overall efficacy and oncological safety of the flap based on a prospective audit of 229 cases done at a high volume cancer center from october 2004 to september 2012 and concludes that SMIF is a oncologically safe,reliable reconstructive option in carefully selected oral cancers undergoing surgical resections.

Anterior skull base reconstruction after cranio-facial resections using galeal pericranial flap.

The tumors of the anterior cranial cavity can either be malignant or benign. They usually arise in the nasal or Para nasal sinuses. Treatment of these tumors includes major craniofacial resection and reconstruction to prevent cerebrospinal fluid leak and meningitis. In this study we are presenting a technique which is simple and cost-effective. We are reporting a series of nine cases in which this technique was tried out and we found that it can be used for dural repair and anterior cranial fossa reconstruction with no major complications.

Schwannoma base tongue: Case report and review of literature.

Schwannomas are benign peripheral nerve sheath tumors. These are rare in the oral cavity (1%). The most common site of involvement in oral cavity is the tongue. Posterior third of tongue is not frequently involved. The aim of this paper is to present a case report of base tongue schwannoma and review literature of this rare tumor. Data from literature were analyzed for age, gender, presenting symptom, size at presentation, and surgical approach. We report a case of 26 year-old male who presented with swelling posterior 1/3rd tongue and change in quality of voice. He was evaluated for the same with MR and incision biopsy and was planned for surgery. Surgery was abandoned at a district hospital due to difficulty in intubation. At our center he underwent fibro optic bronchoscopy guided intubation followed by general anesthesia. He underwent excision of mass using left paramedian lip spitting approach with mandibulotomy and mandibular swing. Tumor was excised in toto. His postoperative recovery was uneventful. Literature review between 2001 and 2012 was done. 15 cases of base tongue schwannoma were identified. The most common age group involved was between 30-40 years. There was a slightly higher incidence in females. All patients were symptomatic at presentation. Most common complaints were related to swallowing and throat pain. Most patients underwent transoral excision of the tumor.

Tobacco related habits among first degree relatives of patients undergoing surgery for advanced head and neck malignancies in India.

This prospective study records the tobacco related habits among the relatives of patients with advanced head and neck cancers who underwent both surgery and chemotherapy as part of their treatment from September 2009 to March 2010. A total of 200 relatives were interviewed (148 males and 52 females). 198 (99%) were aware of the fact that tobacco use can lead to cancer and 168 (84%) had any one of the habits. Smoking alone was reported in 36 (18%) individuals, pan chewing alone in 66 (33%) and multiple habits in 64 (32%). Alcohol and tobacco chewing alone was reported in one case each. There were change in habits following diagnosis of head and neck cancers among the relatives, 33 (16.5%) stopped their habits and smoking was reduced by 25% in 72 (36%)and by 50% in 63 (31.2%) individuals. However, 135 continued the habit even after the diagnosis of cancer in their relatives. Of note, 15 out of the 33 who quit the habit did it because of health advice given to them during the hospital visit.

Multiple ancient schwannoma of the accessory nerve: a case report.

We are reporting a case of multiple ancient schwannoma of the accessory nerve in a 57 year old male. Accessory schwannomas are rare with only 19 cases reported in literature so far. Ancient schwannoma is even rarer in the head and neck region with no other cases associated with the accessory nerve being reported in literature so far.

Anatomic variations of the marginal mandibular nerve.

Marginal Mandibular Nerve (MMN) is a branch of the facial nerve. Muscles supplied by this nerve are responsible for facial symmetry, facial expressions and phonation. Aim was to study the branching pattern and variations in the position of marginal mandibular nerve. 202 patients who underwent neck dissection from June 2005 to October 2006 at Regional Cancer Centre, Trivandrum, India were included in the study. During the course of neck dissection, the marginal mandibular nerve was first identified around the point where the facial artery crossed the lower border of the mandible. Once the nerve was identified, it was traced both backwards and forward till the whole nerve was exposed. Position of the nerve and its relation to lower border of mandible at the point where the facial artery crossed the lower border of the mandible was noted and number and position of each branches were recorded. In 161of the 202 patients (79.7%) the MMN had a single division. Two branches were noted in 26 patients (12.9%). Three branches for MMN are not uncommon, it was noted in 14 patients (6.9%) and in one patient there were four branches. Every effort should be made to preserve all the branches of MMN to ensure cosmesis and decrease morbidity. The mean distance from the lower border of the mandible to the point where the marginal mandibular nerve crossed the facial artery for all the branches taken together was 1.73 mm below the mandible. In 49 patients there was communication between MMN and the cervical branch of facial nerve. The point where the facial artery crosses the lower border of the mandible is a reliable landmark to locate the MMN. Variation in the branching pattern of marginal mandibular nerve is very common.

The submental island flap for reconstruction of intraoral defects in oral cancer patients.

The submental artery island flap (SIF) is gaining acceptance as a simple and reliable option in selected oral oncologic reconstructions. The present study aims to assess the usefulness of submental artery flap in oral reconstruction with respect to flap reliability, cosmesis, function, donor site morbidity and oncological safety. Thirty (30) patients who underwent ablative surgery and reconstruction using the submental artery island flap for oral cancer at Regional Cancer Centre, Trivandrum, India, between October 2004 and December 2006 were prospectively studied for the flap viability, cosmesis, function (speech and swallowing) and locoregional recurrence. The site and stage of the tumour, type of resection, management of the neck and the technique of flap transfer were recorded and the patients were followed up to assess the status of the flap and its donor site and the oncologic outcomes. There were 19 men and 11 women, ages of whom ranged from 30 years to 78 years with a mean+/-SD of 53+/-11 years. With the exception of one patient who had undergone neck dissection as part of a previous surgery, all patients underwent neck dissection or at least a level I clearance along with the wide excision of the primary lesion. The follow up period ranged from 4 to 25 months with a median of 13.5 months. Six patients either recurred locoregionally or had metachronous second primary constituting an over all recurrence rate of 20%. The size of the skin paddle ranged from 3 x 3 cm to 7 x 6 cm, with a mean size of 4.9 x 4 cm. One total and one partial flap loss were observed. One patient had intractable hair growth on the flap even 3 months after surgery. Donor site healing was excellent in all cases and the donor site scar was well hidden. The long term cosmesis and functions were good in all the patients. The submental artery island flap is a simple and reliable option for oral cancer reconstruction in carefully selected cases, with acceptable cosmetic and functional results and reasonable oncological safety.

The role of selective neck dissection (I-III) in the treatment of node negative (N0) neck in oral cancer.

It is now possible to limit the extent of selective neck dissection for mucosal squamous cell carcinoma of the head and neck by sparing selected lymphatic levels thereby reducing the morbidity. This has been brought about by our improved understanding of the metastasis behavior of these cancers. Studies have demonstrated similar rates of neck recurrences and survival after selective neck dissection compared to modified radical neck dissection. The purpose of this study was to evaluate the efficacy of selective neck dissection (SND) in managing the N0 neck in oral cavity carcinomas. A retrospective analysis of Squamous cell carcinoma of oral cavity with N0 neck from 1998 to 2004 was performed. Statistical analysis was done using SPSS software. The chi-square test was used to compare the various proportions. The overall and disease-free survival were estimated using the Kaplan-Meier method and statistical significant difference in survival was tested by log rank test. Out of the 219 cases, 84% were in the early stage and 16% were in the late stages. Seventy two percent of the patients had primary tumors in the anterior two-thirds of the tongue. One hundred and sixty one patients were pathologically node negative. There was no statistically significant difference in the regional recurrence between the pN0 and pN+ patients. There was no difference in the regional recurrence inside and outside the surgical field. The pathological node positive patients had a worse disease-free survival (DFS) compared to the node negative patients, and the patients with nodal recurrence had a significantly worse DFS compared to patients without nodal recurrence. SND (I-III) is a sound and effective procedure in the management of clinically negative neck in squamous cell carcinoma of the oral cavity. Clinically N0 neck but pathologically N+ neck requires adjuvant radiation therapy. It probably has a therapeutic role in the selected cases of squamous cell carcinoma of the oral cavity with N1 neck, and in these cases an extension of dissection to levels IV and V is beneficial.

Metastatic osteosarcoma causing intussusception.

Osteosarcoma is the most common malignant bone neoplasm. It has a very high metastatic potential, and lungs are the most common site of metastasis followed by bones. Multiagent chemotherapy has been reported to alter the biological behavior of the disease so that the tumor metastasizes to more rare sites such as brain, bowel, and soft tissues. The authors report a case of jejuno-jejunal intussusception caused by metastases from osteosarcoma.