Treatment Of Advanced Cases Research Articles

A retrospective study of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers

Objectives Although the Pipelle endometrial biopsy is widely performed as a practical and minimally invasive test for endometrial disease(s), its effectiveness in ovarian cancer has not been explored. The aim of the present study was to evaluate the results of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers. Methods A pre-treatment Pipelle-endometrial biopsy was performed in 90 patients with ovarian, fallopian tube, or peritoneal cancers between January 2014 and November 2021. We retrospectively analysed the association between the results of Pipelle endometrial biopsy and clinicopathological data. Moreover, we evaluated their impact on the following treatment in advanced cases initially treated with chemotherapy. Results The sensitivity and false-negative rates for Pipelle endometrial biopsy were 25/90 (27.8%) and 65/90 (72.2%) in all patients, respectively, and 23/56 (41.0%) and 33/56 (58.9%) in cases with advanced disease (stages III and IV), respectively. Pipelle-positive endometrial biopsy-positive (Pipelle-positive) was not observed in 29 patients with clinical stage I disease, and Pipelle-positive patients exhibited significantly more high-grade serous carcinomas, and positive peritoneal, endometrial, and cervical cytologies than Pipelle-endometrial biopsy-negative cases. Surgical pathology was confirmed in 23 Pipelle-positive patients, and 17/23 (74.0%) had the same diagnosis as that for Pipelle endometrial biopsy. Conversely, 6/23 (26.0%) patients exhibited a minor diagnostic discrepancy between Pipelle endometrial biopsy and surgical pathology. Nineteen of the 38 (50.0%) patients initially treated with chemotherapy were identified as Pipelle-positive, contributing to a prompt histological diagnosis and pre-treatment tumour sampling. Companion diagnostic tests were performed using Pipelle endometrial biopsy samples from 4 inoperable patients. Conclusion Although the positive rate of Pipelle endometrial biopsy in ovarian, fallopian tube, and peritoneal cancers is low, Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease.

A Decade of Therapeutic Challenges in Synchronous Gynecological Cancers from the Bucharest Oncological Institute.

The aim of our study is to present the particularities of a specific subset of gynecological cancer patients in Romania. We present a review of synchronous gynecological neoplasia (SGN) treated in the Bucharest Oncological Institute's surgery departments over a decade. Between 2012 and 2022, 7419 female patients with genital malignancies were treated. We identified 36 patients with invasive synchronous primary gynecological cancers (0.5%) and 12 cases with one primary gynecological and another primary invasive pelvic cancer (rectal/bladder). All recurrent, metastatic, or metachronous tumors detected were excluded. Demographic data, personal history, presenting symptoms, pathologic findings, staging, treatment, and evolution for each case were recorded. Usually, the most common SGN association is between ovarian and endometrial cancer of endometrioid differentiation (low-grade malignancies with very good prognosis). However, we noticed that, given the particularities of the Romanian medical system, the most frequent association is between cervical and endometrial, followed by cervical and ovarian cancers. Moreover, the cancer stage at diagnosis is more advanced. In countries with low HPV vaccination rate and low adherence to screening programs, SGNs can present as extremely advanced cases and require extensive surgery (such as pelvic exenterations) to achieve radicality. This multimodal treatment in advanced cases with high tumor burden determines a reduction in survival, time until progression, and quality of life.

Abstract 2855: Epithelial-mesenchymal transition profile after cisplatin-resistance induction in OSCC cell line

Abstract Oral cancer is among the most common types of cancer in humans. Chemotherapy, mainly based on cisplatin, is utilized in the treatment of advanced cases. However, a loss of chemotherapy effectiveness is frequent and can be related to both inherent or acquired resistance to the chemotherapy agent, resulting in high relapse rates. Epithelial-mesenchymal transition (EMT) plays an important role in different stages of cancer, and it is correlated to resistance to therapy, but the process is still unclear. The purpose of this study is to explore EMT markers in a cisplatin resistant-based model. After determination of IC50, SCC9 cells were intermittently exposed to stepwise increasing concentrations of cisplatin, and Resistance Index (RI) was calculated. Population Doubling (PD) and Population Doubling Time (PDT) were calculated counting the number of viable cells using Trypan Blue method. Scratch assay was performed to investigate the impact on cellular migration. EMT-correlated markers were accessed by RT-qPCR and western blot. After 4 intermittent exposures to cisplatin, we obtained different clones with cisplatin resistance level, SCC9/CPR5 (intermediate cisplatin resistance) and SCC9/CPR11 (final cisplatin resistance) the SCC9/CPR5 clone was obtained showing a mixed morphology between polygonal and fusiform. The complete fusiform morphology resembling mesenchymal cells was seen in SCC9/CPR11, which demonstrated 2-fold of cisplatin resistance in comparison to parental cell line. SCC9/CPR11 showed a difference of less than 1.16 PD and more than 15.5 hours PDT in relation to SCC9. Interestingly, the migratory profile was increased in SCC9/CPR5. Snail1 and Vimentin mRNA levels and protein expression were increased at SCC9/CPR11, but surprisingly E-cadherin was overexpressed but not in protein level. Others markers such as Zeb1, N-cadherin, Vimentin, Snail2 and Twist showed an increase in mRNA levels only in SCC-9-CPR11, however only Twist exhibited high protein expression. Our study showed the establishment of cisplatin resistant SCC9 cells in different moments in relation to a resistance level based on the main two protein markers of EMT, Snail1 and Vimentin. Our data need to be further validated in larger well characterized techniques and we further envision investigating the epigenetic in DNA damage pathways correlating with cisplatin resistance and EMT status. Citation Format: Dieila Giomo De Lima, Gabriell Bonifácio Borgato, Gustavo Narvaes Guimarães, Débora Campanella Bastos, Ricardo Della Coletta, Ana Paula De Souza. Epithelial-mesenchymal transition profile after cisplatin-resistance induction in OSCC cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2855.

New Aspects of Solution Feasibility in a Context of Personalized Therapy Optimization

In this work, the feasibility of a personalized therapy design is considered. We attempt to determine whether all of the obtained results of computer simulations should be presented to medical personnel. For this purpose, a two-drug displacement problem was used, which is the starting point of this research work. The relationships that can be used to characterize the progress as well as the efficiency of treatment in advanced cases can be modeled by a system of nonlinear dynamical equations with additional algebraic dependencies (differential-algebraic equations, DAEs). Then, to improve the efficiency of the therapy, an optimization task needs to be formulated and solved. The solution should meet all the assumed requirements and expectations. Therefore, a control vector parametrization (CVP) procedure for a DAE model is often suggested as an appropriate tool for solving the optimization-based therapy design tasks. In this work, a general iterative optimization framework is discussed in detail together with the proposed three levels of solution feasibility which try to decide if the iteratively obtained solution is trustworthy. The CVP optimization procedure with the designed levels of solution feasibility are implemented and tested. The obtained results are discussed from the perspective of their practical use in the treatment process. It is worth noting that solutions that are valuable from the perspective of creating new optimization algorithms may be rejected by the final recipient as devoid of application possibilities. Some of the presented solutions can be considered as a reference in further clinical research.

Copper(II) Complex Containing 4-Fluorophenoxyacetic Acid Hydrazide and 1,10-Phenanthroline: A Prostate Cancer Cell-Selective and Low-Toxic Copper(II) Compound.

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa.

Trends of Molecular Testing for Lung Cancer at the King Faisal Hospital, Kigali: Therapeutic and Survival Implications

IntroductionLung cancer is the leading cause of cancer mortality worldwide, both in high and low resource settings. Knowledge has been generated elsewhere regarding molecular subtyping and subsequent targeted therapy development, contributing substantially to patient survival. Little is known on the data around lung cancer and its treatment outcomes in Sub-Saharan Africa. This study describes the experience in lung cancer diagnosis, molecular and biomarker testing, and treatment for advanced cases in a single institution in East Africa, between the years 2019 and 2021. MethodsThis was a retrospective observational study evaluating patients with metastatic (stage IV) lung cancer. Data on patient demographics, histologic diagnosis, molecular and biomarker testing, and treatment details and outcomes were collected. Molecular test results were reported as positive if there were biomarkers identified (e.g., EGFR, ALK, programmed death-ligand 1), and patients who had negative test results were reported as negative for biomarkers. ResultsA total of 14 patients were diagnosed with having stage IV disease, and all were proposed to undergo molecular testing. For 12 (86%) patients who were able to have molecular testing done, EGFR and programmed death-ligand 1 were the most common with 66.7% (N = 8) of tissues with either finding. For all 14 patients, treatment changes were made for eight patients (57.1%) after being primarily placed on a combination of paclitaxel and carboplatin for an average of six cycles. Changing treatment significantly improved the 2-year overall survival (85% versus 25%, p = 0.0006). ConclusionsDespite being the number one cause of mortality, gains are being made in poor-resource settings to improve the survival of patients with advanced lung cancers. Limitations to this quest remain misdiagnosis and delayed diagnosis and resource constraints for both molecular testing and subsequent treatments.

Mitotane treatment in adrenocortical carcinoma: mechanisms of action and predictive markers of response to therapy.

Adrenocortical carcinoma (ACC) is a rare malignancy with a high risk of recurrence even in cases with complete surgical tumor resection. Mitotane represents the cornerstone of the adjuvant therapy as well as the first line of medical treatment in advanced cases. However, evidence on mitotane efficacy is mostly based on retrospective studies and the use of mitotane continues to represent a clinical challenge. Mitotane causes selective damage to adrenocortical cells, causing an increase of cell apoptosis through a disruption of mitochondria and the induction of the endoplasmic reticulum stress. Different clinical and molecular markers predicting response to mitotane have been proposed with uncertain results. Attainment of mitotane plasma levels within the target range of 14 to 20 mg/L represent the strongest predictor of mitotane effectiveness both in adjuvant and advanced tumor setting. The occurrence of late recurrence after primary ACC diagnosis and changes in metabolic activity on FDG-PET are only weakly associated with mitotane response. Among the proposed molecular markers associated with mitotane efficacy, the investigation of the CYP2W1*6 and CYP2B6*6 single nucleotide polymorphisms appears to be currently the most promising predictive molecular markers of mitotane therapy. However, none of the evaluated markers has been validated for clinical use. In the era of precision medicine, a better insight into mitotane molecular mechanisms as well as the potential use in the daily clinical practice of clinical parameters and molecular markers predicting the individual response to mitotane are urgently needed.

Long lasting response with trabectedin monotherapy in relapsed metastatic mesenchymal chondrosarcoma

BackgroundMesenchymal chondrosarcoma is an exceedingly rare malignancy, accounting for around 5% of all patients with chondrosarcoma. It is a translocation-related sarcoma that tends to have both local and distant recurrences. Surgery is the mainstay of treatment in localised cases however treatment of advanced cases remains a challenge. The rarity of the disease precludes dedicated clinical trials and hence guidelines for its management are not well defined. The dearth in literature makes it pertinent that the cases treated with newer therapies must be reported to contribute to existing knowledge.Case presentationWe hereby report a case of a 39-year old male without any comorbidity presenting with pelvic pain and was diagnosed as mesenchymal chondrosarcoma of the pelvis. He underwent an initial curative resection followed by a disease-free interval of 7 months. Subsequently, he was treated with pulmonary metastatectomy and local debulking surgery at time of initial relapse. He was then exposed to multiple lines of palliative chemotherapy, which limited our treatment options upon subsequent disease progression. Based on recent data, the patient was given trabectedin monotherapy as fourth line chemotherapy. He tolerated the therapy well and attained a progression-free survival of 12 months, which is an impactful figure in relapsed setting in this patient population.ConclusionThis report aims to present a comprehensive review into available and newer treatment choices for mesenchymal chondrosarcoma, and to highlight trabectedin monotherapy as a possible therapeutic option for mesenchymal chondrosarcoma in the relapsed setting.

Major and minor salivary gland tumours.

Salivary glands carcinomas are very rare epithelial malignant tumors. In 2013 in Europe, 7800 new diagnoses were estimated, 8.5 % of all head and neck cancer. The last WHO classification (2017) counts more than 20 malignant histotypes, this variety as well as the rarity of some of them needs a skilled pathologist for diagnosis. Surgery remains the mainstay of management followed by radiation in high-grade and high-risk pathological features cases. The intensity modulated radiotherapy (IMRT) should be preferred over conformational radiotherapy techniques as adjuvant and exclusive treatment in advanced cases. Particle radiotherapy (i.e. protons, carbon ions) can have a role in advanced/unresectable disease since it was proved to have better results over photons in loco-regional control both in adenoid cystic carcinoma and in other histotypes. Although chemotherapy is still the most frequent treatment for metastatic patients, several new compounds (i.e. anti-angiogenic agents, tailored agents, checkpoint inhibitors) are under investigation.

Metformin attenuates hypoxia-induced resistance to cisplatin in the HepG2 cell line.

Hepatoblastoma is the most commonly occurring liver tumor in children. Preoperative chemotherapy and surgery have improved treatment outcomes; however, further improvements are required in the treatment of advanced cases. Recently, the efficacy of transarterial chemoembolization (TACE) has garnered attention. TACE increases the local concentration of drugs by transcatheterically administering antitumor agents, and induces necrosis in the tumor by embolizing the feeding artery. However, studies have revealed that tumors exhibit resistance to anticancer drugs in hypoxic environments. Metformin is a drug used to treat type 2 diabetes; however, recent reports have indicated that it may also exhibit antitumor effects in various cancer cell lines. These effects are hypothesized to be mediated by the activation of adenosine monophosphate-activated protein kinase and reduction of mammalian target of rapamycin signaling, but these effects occur at high concentrations that are not suitable for use in a clinical setting. The potential efficacy of metformin at increased physiological concentrations has not been evaluated. The present study investigated the therapeutic effect of low concentrations of metformin in combination with cisplatin on liver cancer HepG2 cells in hypoxic conditions. HepG2 cells were treated with cisplatin alone, metformin alone, or a combination of these two drugs and cultured in normoxia or hypoxia. Treatment with either 5 µM cisplatin or 1 mM metformin alone did not significantly affect cell proliferation or apoptosis in hypoxic conditions. However, when 5 µM cisplatin was combined with 1 mM metformin, a significant inhibition of cell proliferation and induction of apoptosis was observed in hypoxic HepG2 cells. In conclusion, a low concentration of metformin attenuates hypoxia-induced resistance to cisplatin in HepG2 cells. Selective delivery of an effective dose of metformin to a hepatoblastoma tumor may be achievable and clinically useful with TACE.

Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer.

Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. The study was conducted at the University of Colorado Hospital. Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. There were no interventions. Immune markers were analyzed for association with disease severity. Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3(+) (P < .0001), PD-1(+)CD8(+) (P = .0058), and PD-1(+)CD4(+) (P = .0104) T cells were enriched in DTC biopsies. CD8(+) and FoxP3(+) T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1(+) lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAF(V600E) mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer.

Long non-coding RNA Linc-ITGB1 knockdown inhibits cell migration and invasion in GBC-SD/M and GBC-SD gallbladder cancer cell lines.

Gallbladder cancer is a highly aggressive malignancy with a low 5-year survival rate. Despite advances in the molecular understanding of the initiation and progression in gallbladder cancer, treatment modalities such as surgery, radiotherapy, or chemotherapy in advanced cases did not yield promising outcomes. Therefore, it is of great importance to uncover new mechanism underlying gallbladder cancer growth and metastasis. In this study, we identified a differentially expressed long intergenic non-coding RNA, linc-ITGB1, in a pair of higher and lower metastatic gallbladder cancer cell sublines. Then, the potential role of linc-ITGB1 in gallbladder cancer cell proliferation, migration, and invasion was explored using a lentivirus-mediated RNA interference system. Functional analysis showed that knockdown of linc-ITGB1 significantly inhibited gallbladder cancer cell proliferation. Moreover, cell migration and invasion were reduced by over twofold in linc-ITGB1 knockdown cells probably due to upregulation of β-catenin and downregulation of vimentin, slug, and TCF8. In conclusion, linc-ITGB1 potentially promoted gallbladder cancer invasion and metastasis by accelerating the process of epithelial-to-mesenchymal transition, and the application of RNA interference targeting linc-ITGB1 might be a potential form of gallbladder cancer treatment in advanced cases.

Can levodopa-induced dyskinesias go beyond the motor circuit?

This scientific commentary refers to ‘A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias’ by Cerasa et al. (doi: 10.1093/brain/awu329). Pioneers of levodopa treatment for Parkinson’s disease in the 1960s quickly realized that the dramatic motor improvement was often clouded by the occurrence of involuntary movements never previously seen in the disorder (Lees et al. , 2015). Levodopa-induced dyskinesias (LIDs) have been a common problem ever since and are one of the main reasons for recommending surgical treatment in advanced cases of Parkinson’s disease. In this issue of Brain , Cerasa and colleagues test the hypothesis that LIDs arise not only from the compromised basal ganglia motor circuit at the heart of Parkinson’s disease but from disturbances in areas of frontal cortex (Cerasa et al. , 2015). LIDs comprise a range of abnormal movements that may be distinguished according to presentation and type. The most common are choreic and sometimes dystonic movements that coincide with high plasma levodopa levels and maximal anti-parkinsonian benefit; hence, these are referred to as ‘peak dose’ or ‘ON’ period dyskinesia (Fahn, 2000). Experimental models are limited to such ‘peak dose’ presentation, which is the most studied type of LID. However, the pathophysiological mechanisms that cause LIDs are still incompletely understood. Classically, it has been proposed that LIDs are related to the degree of nigrostriatal neurodegeneration and striatal changes associated with chronic levodopa therapy (Obeso et al. , 2000). These interact to induce plastic synaptic abnormalities in striatal medium spiny neurons, which has the effect …

SPONTANEOUS CERVİCAL EPİDURAL HEMATOMA DUE TO ORAL ANTİCOAGULANT USE

Spontaneous spinal epidural hematoma (SCEH) is a considerbaly rare clinical condition. It may lead to persistent neurological deficits or even death unless recognized and treated early in its course. It usually occurs after trauma but m ay also develop spontaneously. Majority of cases can be diagnosed with a detailed neurological examination and magnetic resonance imaging (MRI). Urgent surgical tehrapy is the preferred mode of trea tment in advanced cases while a conservative approach is s elected for cases with mild neurological deficit. MRI is regarded as the imaging modality of choice fort he diagnosis of SCEH . We report a case of nontrumatic SCEH after oral anticoagulant (OAC) use that presented with sudden - onset paraplegia. We also revi ewed the relevant literature.

In vitro efficacy of MAGMAS inhibition in prostate cancer.

281 Background: Prostate cancer is the second most common cancer worldwide in males. The initial treatment in advanced cases is medical or surgical castration. The outlook declines when prostate cancer advances independently, despite the aforementioned castration. Within the last ten years, a handful of new agents have proven effective in this castration-resistant phase, but finding more effective, novel ways of treating advanced prostate cancer is warranted. MAGMAS (mitochondria-associated, granulocyte-macrophage colony stimulating factor (GM-CSF) signaling molecule) is a protein ubiquitously expressed in eukaryotic cells that plays a key role in embryonal development in a variety of species. Overexpression of MAGMAS has anti-apoptotic effects, as GM-CSF is a growth factor essential for survival, proliferation and differentiation of cells. MAGMAS and GM-CSF receptor levels have been shown to be overexpressed in prostate cancer, but do not correlate with pathological grade or clinical stage. The purpose of our study was to evaluate the efficacy of a MAGMAS inhibitor, synthesized by Dr Bhaskar Das, in androgen-dependent and androgen-independent prostate cancer cell lines, as well as in a normal prostate cell line as another control. Methods: The different cell lines were treated with MAGMAS inhibitor at various concentrations in vitro. For analysis, we used MTT Cell Proliferation assay at 24 and 48 hours, per manufacturer’s protocol. We tested MAGMAS inhibitor effect on apoptosis/necrosis, cell migration and microtubule destabilization as well. Results: After prostate cancer cell lines were treated with MAGMAS inhibitor in vitro, cell proliferation and migration decreased, apoptosis and necrosis were induced, and microtubules were destabilized, all showing more impressive results in the androgen-independent cells. MAGMAS inhibition did not affect cell proliferation in the normal prostate cells. Conclusions: In vitro studies show MAGMAS inhibition proves efficacious in both androgen-dependent and androgen-independent prostate cancer cell lines. This will be evaluated further in a xenograft mouse model.

Chemoradiotherapy for highly advanced gastric cancer.

121 Background: Although the prognosis of early gastric cancer is favorable, the treatment for advanced cases still have difficulty in achieving satisfactory results. Thus, more effective multimodality treatment should be established. Chemoradiotherapy has become a standard treatment for gastric cancer especially as an adjuvant therapy while radiotherapy has been expected as one of the modalities against highly advanced gastric cancer. Methods: Patients with advanced gastric cancer who were treated with chemotherapy of S-1 and cisplatin plus radiation were analyzed retrospectively. Concurrent radiation therapy (5 days/week) at 2 Gy/day was started with chemotherapy and repeated daily on days 1–5, 8–12, 15–19 and 22–26. Irradiation was planned using a computed tomography (CT) simulator for two rectangular portals with a pair of 45-degree wedge filters and was targeted at the primary tumor and surrounding lesions, including lymph nodes. Results: A total 109 patients were treated with chemoradiotherapy between 2002 and 2013 at our institute. The median age was 64 years. Histological type included 45 differentiated and undifferentiated 64 subtypes. The TNM stage before the treatment was diagnosed as IIIA: 11; IIIB: 10; IIIC: 14; IV: 74. Of the 98 evaluable patients, 69 patients had partial responses while no patients had a complete response, resulting in an overall response rate of 70%. Progressive disease (PD) occurred in 2 patients (4%). The most frequent adverse events more than grade 3 were hematologic toxicities, including leukocytopenia (47%), neutropenia (25%), and thrombocytopenia (24%). Non-hematologic toxicities such as general fatigue, renal-related events, and gastrointestinal toxicities were manageable with no treatment-related death. The median survival time was 537 days. Conclusions: While there were disadvantages of radiotherapy including the difficulty of confirming the area of irradiation due to peristaltic movement, risk of perforation and ulceration, recent technological advancement of radiation therapy has enabled pinpoint accuracy in treatment of primary gastric lesions and regional lymph nodes. There has been much anticipation that chemoradiotherapy will be a part of multidisciplinary treatment for advanced cancer.

Ludwig′s angina - An emergency: A case report with literature review

Ludwig's angina is a form of severe diffuse cellulitis that presents an acute onset and spreads rapidly, bilaterally affecting the submandibular, sublingual and submental spaces resulting in a state of emergency. Early diagnosis and immediate treatment planning could be a life-saving procedure. Here we report a case of wide spread odontogenic infection extending to the neck with elevation of the floor of the mouth obstructing the airway which resulted in breathlessness and stridor for which the patient was directed to maintain his airway by elective tracheostomy and subsequent drainage of the potentially involved spaces. Late stages of the disease should be addressed immediately and given special importance towards the maintenance of airway followed by surgical decompression under antibiotic coverage. The appropriate use of parenteral antibiotics, airway protection techniques, and formal surgical drainage of the infection remains the standard protocol of treatment in advanced cases of Ludwig's angina.

New Insight into the Treatment of Advanced Differentiated Thyroid Cancer

The vast majority of patients with differentiated thyroid cancer (DTC) are treated successfully with surgery and radioactive iodine ablation, yet the treatment of advanced cases is frustrating and largely ineffective. Systemic treatment with conventional cytotoxic chemotherapy is basically ineffective in most patients with advanced DTC. However, a better understanding of the genetics and biologic basis of thyroid cancers has generated opportunities for innovative therapeutic modalities, resulting in several clinical trials. We aim to delineate the latest knowledge regarding the biologic characteristics of DTC and to describe the available data related to novel targeted therapies that have demonstrated clinical effectiveness.

LARYNGECTOMY: FROM STRIDOR TO SURVIVAL- OUR EXPERIENCE

AbstractLaryngeal cancer is among the commonest cancers in the body. It constitutes one fifth of all head and neck cancers. India accounts for 17% of the world burden. Even though it is curable in early stages, majority of them in India present in the later stages due to ignorance and poverty. The mainstay of treatment in advanced cases is total laryngectomy, with or without post operative radiotherapy which results in loss of voice. However, by speech rehabilitation and by modification of the technique in the form of near total laryngectomy, these patients can be assured of good quality disease free survival.

Updated Review of the Pathogenesis and Management of Merkel Cell Carcinoma

Merkel cell carcinoma is a rare, aggressive, malignant cutaneous tumor of the elderly or immunosuppressed individuals that usually appears on sun-exposed areas of the body. Its pathogenesis is still debated, and, currently, no standardized treatment exists. To provide a current updated review of the most relevant data concerning the pathogenesis and management of Merkel cell carcinoma. Using relevant MeSH terms, we performed a review of the literature on these subjects from 1980 to June 2009. The current management of Merkel cell carcinoma is based on surgical excision as the majority of patients present with localized disease, whereas up to 30% have regional lymph node metastases. In these cases, the best outcome is achieved with multidisciplinary management that includes radiotherapy. Chemotherapy is part of the treatment in advanced cases and is mandatory for distant metastatis. Given that a recent work showed the presence of a previously unknown polyomavirus, which the authors called Merkel cell polyomavirus, the therapeutical approach to Merkel cell carcinoma could be reconsidered in the future.