Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

Long-term prognostic impact of circulating tumour cells in gastric cancer patients

AIM To analyse the long-term prognostic impact of circulating tumour cells(CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-m L peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerasespecific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-m L of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant(P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs(P = 0.034).CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

Detection of circulating tumour cells in colorectal cancer:Emerging techniques and clinical implications

Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.

Mutational Analysis of OCT4+ and OCT4− Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

Circulating tumour cells(CTCs)were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer(NSCLC).Octamer-binding transcription factor-4 positive(OCT4+)and negative(OCT4−)CTCs were identified and captured by interphase fluorescence in situ hybridisation(iFISH).Single cell whole exome sequencing(WES)was performed and the corresponding bioinformatics data were analysed.OCT4+cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients.Moreover,the tumour mutational burden(TMB)values observed for OCT4+samples from the same patients were slightly smaller than those of the OCT4−samples;the difference was not statistically significant(P>0.05).Thirteen and six characteristic mutations were found in negative samples and positive samples,respectively.The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.

Regarding on the Fractional Mathematical Model of Tumour Invasion and Metastasis

In this paper,we analyze the behaviour of solution for the system exemplifying model of tumour invasion and metastasis by the help of q-homotopy analysis transform method(q-HATM)with the fractional operator.The analyzed model consists of a system of three nonlinear differential equations elucidating the activation and the migratory response of the degradation of the matrix,tumour cells and production of degradative enzymes by the tumour cells.The considered method is graceful amalgamations of q-homotopy analysis technique with Laplace transform(LT),and Caputo–Fabrizio(CF)fractional operator is hired in the present study.By using the fixed point theory,existence and uniqueness are demonstrated.To validate and present the effectiveness of the considered algorithm,we analyzed the considered system in terms of fractional order with time and space.The error analysis of the considered scheme is illustrated.The variations with small change time with respect to achieved results are effectively captured in plots.The obtained results confirm that the considered method is very efficient and highly methodical to analyze the behaviors of the system of fractional order differential equations.

Perivascular epithelioid cell tumour of the liver

Perivascular epithelioid cell tumour is not uncommon in the liver but seldom malignant.

CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules

Background and objective Low-density computed tomography(LDCT)improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data.Hence,accurate diagnosis of early-stage lung cancer remains challenging.The purpose of the study was to assess the feasibility of using circulating tumour cells(CTCs)to differentiate malignant from benign pulmonary nodules.Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited.Peripheral blood samples were collected before surgery,and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis.Laser capture microdissection,MALBAC amplification,and whole-exome sequencing were performed on 8 samples.The diagnostic efficacy of CTCs counting,and the genomic variation profile of benign and malignant CTCs samples were analysed.Results Using 2.5 cells/5 m L as the cut-off value,the area under the receiver operating characteristic curve was of 0.651(95%confidence interval:0.538-0.764),with a sensitivity and specificity of 0.526 and 0.800,respectively,and positive and negative predictive values of 91.1%and 30.3%,respectively.Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples.TP53 mutations were identified in CTCs of four malignant cases;in particular,g.7578115T>C,g.7578645C>T,and g.7579472G>C were exclusively detected in all four malignant samples.Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules.TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Granular Cell Tumour of Larynx— A Case Report

Granular cell tumors, also called Abrikossoff tumors, are benign, slowly growing neoplasms. They may occur anywhere in the body, but head and neck accounts to 45% - 65% of these cases. The most common site is the tongue. Larynx is relatively an uncommon location for these tumours, accounting for approximately three to 10 per cent of the reported cases. Laryngeal granular cell tumour is extremely rare accounting for only 19 reported cases under the age of 17 years. As many as 10% of patients experience multifocal synchronous or metachronous tumors. We present a rare case report of granular cell tumour of the larynx.

Potential utility of liquid biopsies in the management of patients with biliary tract cancers:A review

Biliary tract cancer,comprising gallbladder cancer,cholangiocarcinoma and ampullary cancer,represents a more uncommon entity outside high-endemic areas,though global incidence is rising.The majority of patients present at a late stage,and 5-year survival remains poor.Advanced stage disease is incurable,and though palliative chemotherapy has been shown to improve survival,further diagnostic and therapeutic options are required in order to improve patient outcomes.Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations,attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness.Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic,predictive and prognostic biomarkers.In this review,the current standard of care for patients with biliary tract cancer,future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed.Circulating tumour DNA,circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer.A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.

Mesenteric metastases from mature teratoma of the testis:A case report

Metastatic spread of testicular cancer has been well documented,with 95% of cases involving para-aortic retroperitoneal lymph nodes.Mesenteric lymphatic basins do not lie within the canonical drainage pathway of the testes and represent a rare site of metastasis.Various mechanisms of spread to the mesentery have been described,including direct extension and haematogenous dissemination.We present a case of a previously-well 43-year-old man who presented with right scrotal discomfort and intermittent lower back pain,who was found to have mesenteric metastases from a non-seminomatous germ cell tumour of the testis.Managing lymphadenopathy that lies outside of standard resection templates remains a complex surgical challenge.Here we present the first case in the English medical literature with co-existing supradiaphragmatic axillary and mediastinal nodal disease.

Real case of primitive embryonal duodenal carcinoma in a young man

We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-year-old man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Gastroscopy revealed a circumferential vegetating lesion on the second portion of the duodenum. The lesion was indurated at the third portion of the duodenum, responsible for a tight stenosis. A computerized tomography-scan of the chest, abdomen and pelvis, and a pancreatic MRI showed a circumferential lesion with a bi-ductal dilatation (i.e., of the common bile duct and Wirsung’s duct) without metastatic localisation. The patient underwent a pancreaticoduodenectomy with lymph node dissection including all cellular adipose tissues of the hepatic pedicle from the hepatic common artery and of the retroportal lamina. Histological findings were suggestive of a duodenal embryonal carcinoma with pancreatic infiltration. This is the second published case highlighting the duodenal primitive localisation of an embryonal carcinoma with pancreatic infiltration.

Transitional cell carcinoma of the ovary – A case report with review of literature

Transitional cell carcinoma （TCC） of the ovary is a rare and recently recognized subtype of ovarian epithelial cancer. We presented the first case report from our Institute （Sheri Kashmir Instiute of Medical Sciences, Srinagar, India）, which was initially rnisdiagnosed as stromal cell carcinoma （granulosa cell tumour）, and on review of histopathology with immunohistochemistry, the diagnosis of TCC of the ovary was established. The aim of this article was to describe the typical case of primary TCC of the ovary and to review the literature for information on TCC management.

Further Analytical Studies on a Mercuri Thiol Adduct Isolated from a Human Prostate Cancer Cell Line (LNCaP)

Thiols play vital roles in cellular metabolism knowledge of which may be important in the design of future anticancer drugs. Previous work on the composition of the thiols present in human cancer cell lines has shown the presence of an unknown low molecular weight species, deemed to be a “Conthiol”, which could be important in this respect. This was prepared and isolated from a human prostate cancer cell line (LNCaP) in the form of an adduct of 2-mercuri-4-nitrophenol;it accounts for 56.5% of the total cellular thiols present in this cell line. Initial LC-MS analysis of this adduct had indicated that the possible molecular weight of the thiol was in the region of 467 daltons. In further analytical studies to identify the thiol, attempts were made to release it from the adduct by passage through a Thiopropyl Sepharose6B column. LC-MS analysis of the column eluate revealed two components yielding negative ion fragments of 427 m/z and 449 m/z. Only the former component contained thiol, indicating that a breakdown and/or possible rearrangement of the Conthiol had occurred. Further investigations of the column thiol eluate using ICP-MS analysis showed that the sulfur content agreed with the spectrophotometric analysis result (Ellman assay) and that the molecule did not contain phosphate. Amino acid analyses of the eluate were negative. In an attempt to prevent the breakdown of the thiol released by the Thiopropyl Sepharose 6B column, the adduct was treated with 5% v/v bromine water prior to applying to the column. In this instance the thiol containing eluate obtained from the column was treated with an equimolar quantity of mercuric chloride forming a fresh adduct, RS-Hg-SR. LC-MS analysis of this mercurial adduct detected a negative ion fragment of 782 m/z which on further ionization gave a ladder like pattern showing loss of mass units of 58 in each rung. This would seem to suggest the presence of a repeat polymer like structure containing 5 monomers, which, plus the thiol atom, gives a possible formula weight of 322;probably revealing only a part of the unknown Conthiol molecule whose properties and formula weight do not correlate with any known cellular thiol. Further analysis of the thiol released from the adduct on the Thiopropyl Sepharose 6B column by Infra-red (FTIR) provided little information except to confirm the presence of the thiol group and C=O stretch bands together with the possibility of a lactam ring at 1651 and 1634 cm·s-1.

Atraumatic groin pain secondary to an aneurysmal bone cyst:A case report and literature review

BACKGROUND Bone lesions can present the multi-displinary team with a challenge by way of diagnosis as some lesions share many radiological and histological characteristics.Giant cell tumours of the bone(GCTB)are relatively common,benign bone tumours.Aneurysmal bone cysts(ABC)are less common benign osteolytic lesions that are histologically similar to GCTBs but produce blood filled cavities.Both GCTBs and ABCs are locally aggressive and are typically found on meta-epiphyseal regions of long bones with pelvic tumours being less common.CASE SUMMARY A 17-year old female presented with atraumatic right groin pain and was initially diagnosed with a GCTB on the right superior pubic ramus of the pelvis.The patient was treated successfully with a wide excision,curettage and bone graft and underwent open reduction and internal fixation of the right hemi-pelvis.Following further intra-operative histological investigations,the lesion was diagnosed as an ABC.CONCLUSION This patient has had an uncomplicated post-operative course,has returned to comfortable weight bearing and will be reviewed for minimum 5 yr in the outpatient setting to monitor for reoccurrence.

Treatment Outcomes of Germ Cell Tumors of Ovary:Single Institutional Study

5%of all ovarian tumours are accounted to germ cell tumours(GCT’s).Affecting mostly young women,the highest incidence is seen in second and third decade of life.They are highly malignant but chemosensitive and more curable than their epithelial counterparts.Treating these tumors with effective surgery and combination chemotherapy survival rates have dramatically improved in recent decades.We present our experience of ovarian germ cell tumours in the department of Surgical Oncology,Rajendra Institute of Medical Sciences(RIMS),Ranchi with special emphasis on treatment outcomes.A retrospective review of hospital medical records of patients with ovarian germ cell tumours diagnosed and treated at RIMS from June 2019 to August 2020,was performed.Clinical profile and treatment outcome of patients were recorded.A total of 19 patients met criteria.The median age at diagnosis was 20 years(range 11-42 years)and all had good performance status.All except two patients underwent surgery,70.6%and 29.4%in upfront and interval debulking surgery(IDS)setting respectively.Fertility preserving surgery was done in 75%patients in the primary surgery group and 60%undergoing IDS.83.3%patients received BEP as adjuvant chemotherapy whereas 80%as neo-adjuvant chemotherapy.Majority(31.5%)patients had dysgerminoma as final histology,followed by mixed histology(26.3%),yolk sac tumour(15.7%),immature teratoma(15.7%)and choriocarcinoma(10.5%).47.3%patients were in Stage I at the time of diagnosis.78.9%patients were alive without disease,10.5%recurred,and 10.5%were lost to follow up.

Cancer stem cells may contribute to the difficulty in treating cancer

Tumour heterogeneity is a phenomenon where each cell that makes up a tumour,contains mutations that differ from that of other cells in the tumour.The clonal evolution and cancer stem cell theories of cancer formation,have been used to explain tumour heterogeneity.The theories both point to the existence of cells within a tumour that are capable of initiating the tumour in a different location.While the clonal evolution theory argues that all cells within a tumour possess this ability,the cancer stem cell theory argues that only a few cells(cancer stem cells or CSCs)within the tumour possess this ability to seed the tumour in a different location.Data supporting the cancer stem cell theory is accumulating.Researchers have targeted these CSCs therapeutically,hypothesizing that since these CSCs are the‘drivers’of tumour progression,their death may inhibit tumour progression.This was foiled by tumour cell plasticity,a phenomenon whereby a non-CSC spontaneously de-differentiates into a CSC.Researchers are now working on combinations that kill both CSCs and non-CSCs as well as drugs that prevent non-CSC-to-CSC transition.This review concisely describes CSCs and how they contribute to the difficulty in treating cancer.

Total Talar Replacement Using a Novel 3D-Printed Prosthesis for Recurrent Giant Cell Tumour of the Talus

In our case,3D printing was used to fabricate a custom-made titanium alloy total talar prosthesis as a mirror image of the contralateral healthy talus for a 16-year-old girl who underwent right talar resection for a recurrent giant cell tumour(GCT)of the talus.A porous surface was used over the neck and tail of the talus prosthesis to promote soft tissue attachment and improve the stability of the prosthesis.Pre-drilled medial and lateral holes were prepared for ligament repair and attachment.Eighteen months after the operation,there was no tumour recurrence,and the patient walked without symptoms.The Musculoskeletal Tumour Society score was 22/30,the American Orthopaedic Foot and Ankle Society score was 88/100,and the prosthesis was well positioned on radiographs.The short-and medium-term outcomes indicated that 3D-printed modular talar prostheses could be an effective treatment option.