Oral Squamous Cell Carcinoma (OSCC)

Background The cellular regulatory protein p53 is overexpressed by almost 50% of all malignancies making it an attractive target for a vaccine approach to cancer. A number of immunotherapy approaches targeting p53 have been evaluated successfully in murine models, but translation of these preclinical Wndings to the clinic has been unsuccessful. Prior studies in our laboratory employing murine models demonstrated that a modiWed vaccinia virus Ankara (MVA) vaccine expressing murine p53 could stimulate p53 speciWc immunity. Systemic administration of the MVA vaccine was able to eVect the rejection of established tumors. To better understand the immunologic mechanisms that underlie the vaccine function of human p53, we utilized a murine model in which the murine germ line copy of p53 was replaced with a modiWed human one. These mice, referred to as Hupki, were evaluated as a tolerant model to explore the capacity of MVA expressing human p53 to overcome tolerance and reject human p53-expressing tumors.

We describe an animal model to induce the histogenesis of squamous metaplasia of the cervical columnar epithelium, a condition usually preceding cervical neoplasia. This model is based on dietary retinoid depletion in female mice. Control sibling mice fed the same diet but with all-trans-retinoic acid (at 3 micrograms/g diet) showed the normal endocervical epithelial and glandular columnar morphology, typical of a simple epithelium without subcolumnar reserve cells. The stratified squamous ectocervical epithelium of these mice fed all-trans retinoic acid showed intense immunohistochemical staining in basal and suprabasal cells with mono-specific antibodies against keratins K5, K14, K6, K13, and, suprabasally, with antibodies specific for K1 and K10. At the squamocolumnar junction, the adjacent columnar epithelium (termed "suprajunctional") did not show staining for K5, K14, K6, K13, K1, and K10 but specifically stained for keratin K8, typical of simple epithelia and absent...

Background: Marjolin's ulcer is a rare but highly aggressive squamous cell cancer that is most often associated with chronic burn wounds. Although many individual case reports exist, no comprehensive evaluation of Marjolin's ulcer patients has been conducted in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our local setting and to identify predictors of outcome. Methods: This was a retrospective study of histologically confirmed cases of Marjolin's ulcer seen at Bugando Medical Centre over a period of 10-years between January 2001 and December 2010. Data were retrieved from patients' files and analyzed using SPSS computer software version 15.0

Objective: Though the surgical treatment of esophageal cancer is increasingly accepted for elderly people defined as aged over 70 years, less is reported about the results in patients over 75. This study is a single institution retrospective analysis of outcome after esophagectomy for cancer of the esophagus and GEJ in patients aged over 75 years. Methods: All consecutive patients 76 years old and over undergoing curative esophagectomy for cancer in the period 1991-2006 were analyzed as to comorbidities, outcome and long-term survival. All the data had been prospectively collected in a database. Postoperative mortality risk was assessed by P-POSSUM and O-POSSUM score for in-hospital mortality and by the recently published Steyerberg's score system [Steyerberg EW, Neville BA, Koppert LB, Lemmens VEPP, Tilanus HW, Coebergh JWW, Weeks JC, Earle CC. Surgical mortality in patients with esophageal cancer: development and validation of a simple risk score. J Clin Oncol 2006;24:4277-84.] for 30-day mortality. Five-year survival was compared to the standardized survival in the general population. Results: One hundred and eight patients fulfilling the abovementioned criteria were found (76 males and 32 females, mean age 79.5 years, mean standardized life-expectancy: 7.36 years). Among them, 69% had esophageal tumors and 31% GEJ tumors. The predominant histology was adenocarcinoma (74%). Eighty-six (79.6%) presented with one or more major comorbidities or a history of previous major upper-GI surgery, potentially affecting the surgical outcome. All underwent resection with curative intent (R 0 83.3%, R 1 12%, R 2 4.6%). The overall postoperative morbidity rate was 51.9%, pulmonary complications (37%) being the most frequent. Postoperative mortality, mainly due to cardiopulmonary complications, was 7.4%, which was consistent with that predicted by P-POSSUM score (7.2%) and lower than that predicted by O-POSSUM score (15.1%). Thirty-day mortality was 5.5%, being consistent with that predicted by the Steyerberg's score (6.8%). Overall 5-year survival was 35.7%, while R 0 overall survival 42% and cancer specific R 0 survival 51.7%. Conclusions: Patients 76 years old and over with esophageal or GEJ cancer should not be denied surgery solely on the basis of age. Outcome and long-term results in the selected elderly are not differing from those reported for younger patients. However, despite thorough preoperative assessment being applied in the selection of the candidates for surgery, a practical and reliable individual riskanalysis stratification is still lacking. #

Background. In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM. Methods. To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1). Results. A cutoff point of CRM at B1.0 mm and[1.0 mm appeared to be an adequate marker for survival and prognosis (both P \ 0.001). The outcome in patients with CRMs B1.0 and [0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P \ 0.001). Survival of patients

The combination of a myocutaneous flap with a three dimensional, bendable reconstruction plate has provided very satisfactory results in restoration of mandibular defects following surgical resections in irradiated patients. Twenty-four cases have been treated and evaluated prospectively using this technique. Patients requiring postoperative irradiation were excluded from this study. Two groups were identified. Group A (n=20) required a myocutaneous flap to resurface the soft tissue defect and Group B (n=4) were treated by primary closure. No failures were encountered in the group handled primarily with a myocutaneous flap combined with an A 0 plate. One failure occurred in the group closed primarily. Nine (38%) of the patients have maintained their plate for over 1 year. Twelve (55'10) have functioned for more than 9 months. Of the remaining three (7%), one failed and the other two have been in place for more than 5 months. The results of this study demonstrate that a well-vascularized soft tissue bed in combination with stainless steel plate provides a very satisfactory, functional, esthetic and reliable method in rehabilitation of mandibular defects primarily in irradiated patients.

BACKGROUND: Genetic polymorphisms of vitamin D receptor gene (VDR) and genes involved in vitamin D metabolism pathway, CYP27B1 and CYP24B1, may affect individual susceptibility to oral squamous cell carcinoma. The purpose of this study was to evaluate the associations between VDR, CYP27B1 and CYP24A1 gene polymorphisms with oral cancer risk and survival. METHODS: Study cohort consisted of 110 patients with oral cancer and 122 healthy controls. The genotypes of the analysed genes were determined by PCR-RFLP or real-time PCR method. RESULTS: The significant decrease of oral cancer risk was observed in individuals with heterozygote genotype of CYP24A1 gene (rs2296241) (odds ratio 0.281, P = 0.000) in comparison with wild type. Patients with VDR FokI ff wild type genotype had significantly worse overall survival (P = 0.012, log rank) compared with heterozygous and mutated genotype combined. A stratified analysis by the lymph node involvement and tumour stage showed that ff is associated with poor survival in groups with and without lymph node involvement (P = 0.025, P = 0.040, respectively) and in stage III tumours (P = 0.026). Multivariate Cox's regression analysis revealed that VDR FokI could be considered an independent prognostic factor. CONCLUSION: Our findings indicate that CYP24A1 gene polymorphism might have an influence on the susceptibility to oral cancer. VDR FokI polymorphism was associated with worse survival and could be considered as an independent prognostic marker.