Management of Malignants Gliomas: About 20 Cases Treated in the Medical Oncology Department of Fattouma Bourguiba University Hospital-Monastir

Introduction: Malignant gliomas refer to grade III or IV brain tumors defined according to the World Health Organization (WHO) classification. They are a heterogeneous group of pathologies and represent a serious health problem by their frequency, severity and treatment difficulties. The prognosis of malignant gliomas remains poor despite all the medical advances. Materials and Methods: It is a retrospective study included 20 cases of malignant glial tumors treated at the medical oncology department, Fattouma Bourguiba hospital in Monastir between 2012 and 2016, according to the STUPP protocol. Results: These were 12 men and 8 women with a median age of 43. Clinical signs were not very specific, dominated by intracranial hypertension and deficit signs. Imagery referred to the diagnosis of malignant gliomas in 1st intention. Surgery consisted of a macroscopically complete exeresis in (15%) cases, a partial exeresis in (50%), the rest of the patients had a stereotactic biopsy. Histology found GBM in 16 patients (80%), 2 cases of Grade III anaplastic astrocytoma (10%), 1 case of anaplastic oligodendroglioma (5%), and 1 case of Grade III anaplastic eppendymoma (5%). Most of our patients received concurrent radio-chemotherapy and adjuvant TMZ chemotherapy was administered in 15 patients, 7 of whom received the full 6 scheduled cures. A relapse treatment was decided in only one of the 12 patients who relapsed. 6 patients are still alive. The median survival is 11.27 months. In our series, overall survival was related to histological type (p = 0.006) and neurological status assessed at the end of RT-CT (p = 0.001). While age, general condition score, type of surgery, and post-therapeutic development did not show a statistically significant relationship, although survival rates were consistent with the criteria assessed. Conclusion: Malignant gliomas are rare tumors, bad prognosis, aggravated in Tunisia by a diagnostic delay. The creation of a multidisciplinary neuro-oncology group can help to improve management.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Paclitaxel for second-line treatment of squamous cell carcinoma of the head and neck:A multicenter retrospective Italian study

BACKGROUND Squamous cell carcinoma of the head and neck(SCCHN)accounts for 3%of all malignant tumors in Italy.Immune checkpoint inhibitors combined with chemotherapy is first-line treatment for SCCHN;however,second-line treatment options are limited.Taxanes are widely used for combination therapy of SCCHN,as clinical trials have shown their efficacy in patients with this disease,partic ularly in patients with prior therapy.AIM To perform a multicenter retrospective study on the efficacy and safety of weekly paclitaxel for SCCHN.METHODS All patients were previously treated with at least one systemic therapy regimen,which included platinum-based therapy in the vast majority.No patient received prior immunotherapy.RESULTS Median progression-free survival(mPFS)was 3.4 months and median overall survival(mOS)was 6.5 months.Subgroup analysis was performed according to three principal prognostic factors:Smoking,alcohol consumption,and body mass index.Analysis demonstrated reduced survival,both mOS and mPFS,in the unfavorable prognostic groups,with the biggest deltas observed in mOS.CONCLUSION Weekly paclitaxel provided favorable survival and disease control rates,with low severe adverse events.Paclitaxel is a safe and valid therapeutic option for patients with SCCHN who received prior therapy.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is(limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Therapeutic Itinerary of Patients Followed for Connectivitis in the Internal Medicine Department of the CNHU-HKM of Cotonou (Benin)

Introduction: In black Africa, connectivites have been for a long time a source of diagnostic erraticity because of their clinical polymorphism. This study aims to determine the therapeutic itinerary of patients followed for connectivitis in the Internal Medicine Department of the CNHU HKM of Cotonou. Methodology: This is a cross-sectional study that included patients followed for connectivitis in the HKM-Cotonou Internal Medicine Department from January 2010 to October 2018. Results: Out of 3600 patients hospitalized in the study period, 21 had connectivitis, i.e. a hospital frequency of 0.58%. Of the 21 patients collected, 18 met the inclusion criteria. The mean age was 40 (±11) years old and the youngest was of 21 and the oldest 58. The sex ratio was 17.9. The “Fon” ethnic group was the most represented (33.3%) and 15 (83.3%) subjects were Christians. Systemic lupus erythematosus was the most frequent connectivitis (55.6%). The average time of consultation was 38 months. Witchcraft was the most incriminating cause (78%). Ten (55.5%) patients had resorted to self-medication as their first choice of treatment, 5 (27.8%) to traditional medicine treatment and 3 (16.7%) to prayer for healing. The reasons for the first choice of treatment were satisfaction (44.4%), financial problems (27.8%), trivialization of the disease (16.7%), and advice from family and friends (11.1%). The consultation at the CNHU followed a referral from a first contact health structure (61%) or an initiative of the patient (27.8%). Conclusion: Connectivitis is a source of diagnostic error in our context. Awareness must be raised among patients for an early consultation at the first symptoms.

Prevention,diagnostic evaluation,management and prognostic implications of liver disease in critically ill patients with COVID-19

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2,broke out in December 2019 in Wuhan city of China and spread rapidly worldwide.Therefore,by March 2020,the World Health Organization declared the disease a global pandemic.Apart from the respiratory system,various other organs of the human body are also seriously affected by the virus.Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%.Elevated levels of total bilirubin,aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings.Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury.This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19,the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients.Moreover,it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.

Small Cell Lymphoma of the Gastrocnemius Muscle: A Case Report

Introduction: The primary localization of non-Hodgkin lymphoma of the muscle is rare. Only the biopsy allows the certainty diagnosis. The aim was to report a first case of small cell lymphoma of the gastrocnemius in Mali and to do a review of the literature. Clinical Observation: It was about a 34-year-old woman who consulted 3 months after the onset of symptoms for swelling and pain in the left calf. On clinical examination there was a hard, painful and warm mass in the left calf, with paresthesias in the tibial nerve territory associated with partial functional impotence of the leg. The ultrasound revealed a hyper echogenic and heterogeneous non-vascularized mass of the left gastrocnemius muscle measuring 65 × 45 × 40 mm non-vascularized on color Doppler and pulsed in favor of myositis. Magnetic resonance imaging (MRI) concluded in a well-limited heterogeneous cystic mass in the left gastrocnemius muscle respecting the bone of benign appearance: remodeled Baker’s cyst? Considering the radioclinical unconformity, thoraco-abdominal CT was performed and revealed pulmonary metastasis. The biopsy carried out concluded with a small cell lymphoma of the gastrocnemial muscle. Marginal resection was performed associated with adjuvant chemotherapy. The advancement at 9 months was satisfactory.

Gynecological Side Effects of Tamoxifen among Sudanese Women, Khartoum, Sudan, 2020

Background: In Sudan, the common endocrine therapy tamoxifen is prescribed to HR-positive patients, which is associated with a variety of complications such as hot flashes, vaginal discharge, and vaginal dryness. Objective: This study aimed to determine the gynecological side effects of tamoxifen among Sudanese women who have been diagnosed with breast cancer in Khartoum, Sudan. Methods: A retrospective cross-sectional study was conducted at Alzara Hospital in Al Amal Toure Revere, Sudan. A convenience sample of individuals previously diagnosed with breast cancer attended refer clinic. From October 2020 to September 2021, all patients attending were checked for eligibility. Results: A total of 100 patients were enrolled in the study;60% of patients reported increased vaginal secretions after taking the drug, 28% reported normal vaginal secretions with no change, and 11% reported decreased secretions after taking the medication, while 22% developed vaginal bleeding, and 22% of the ultrasound results revealed endometrial masses among the study patients. Also, 54 percent of female patients experienced hot flashes after taking the medication, and 12% of women missed some doses of treatment. Conclusion: Tamoxifen results in several gynecological side effects in women with breast cancer. A high percentage of women in the study developed hot flashes, vaginal bleeding, and discharge, in addition to having ultrasound results showing endometrial masses among them.

Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients

Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cells(MSCs)are critical for BM/bone homeostasis,and failures in their functionality,transform the BM into a premetastatic niche(PMN).We previously found that BM-MSCs from advanced breast cancer patients(BCPs,infiltrative ductal carcinoma,stage III-B)have an abnormal profile.This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients.A comparative analysis was undertaken,which included self-renewal capacity,morphology,proliferation capacity,cell cycle,reactive oxygen species(ROS)levels,and senescence-associatedβ‑galactosidase(SA‑β‑gal)staining of BMderived MSCs isolated from 14 BCPs and 9 healthy volunteers(HVs).Additionally,the expression and activity of the telomerase subunit TERT,as well as telomere length,were measured.Expression levels of pluripotency,osteogenic,and osteoclastogenic genes(OCT-4,SOX-2,M-CAM,RUNX-2,BMP-2,CCL-2,M-CSF,and IL-6)were also determined.The results showed that MSCs from BCPs had reduced,self-renewal and proliferation capacity.These cells also exhibited inhibited cell cycle progression and phenotypic changes,such as an enlarged and flattened appearance.Additionally,there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length.We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression.We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.

The concept of “prevention before disease” in Buddhism and its application & dissemination status in modern medicine: a review

The concept of“prevention before disease”in Buddhism has deep roots in traditional Indian medicine and has been integrated into Buddhist philosophy.The Buddhist philosophy of“prevention before disease”is based on the cultivation of mindfulness through the practice of meditation.This philosophy has been integrated into modern medicine through the development of mindfulness-based interventions,which have been found to be effective in reducing symptoms of anxiety,depression,and chronic pain.The article also discusses the spread of Buddhist philosophy and its“prevention before disease”concept in different regions of the world and the potential benefits of integrating this philosophy into patient care.Here,we summarized the concept of“Prevention before Disease”in Buddhism and its specific content in Buddhist teachings and discussed its application&dissemination status in modern medicine.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

Genomic medicine and cancer clinical trial in Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic disease.Because chemotherapy empirically affects all dividing cells,the targets are virtually non-specific.In this regard,toxic effects on normal tissue are essentially inevitable.

Erratum to Treatment strategies for patients with HER2-positive gastric cancer

For the affiliation information,the affiliation for author Feixue Wang should be Department of GI Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin Medical University,Tianjin 300060,China.

Real-World Evidence in Localized Pancreatic: Coping with Uncertainty in Unselected Populations

Background: Localized pancreatic cancer, including resectable (R), borderline resectable (BR) and locally advanced unresectable disease (LAU), is considered in clinical guidelines for diverse treatment options based on clinical trials in selected populations. Hence, exploring with real world evidence (RWE) clinicians’ preferences for treatment options and their results seems pertinent. Methods: In a set of consecutive patients with localized pancreatic cancer assisted in a third level hospital from January 2013 to December 2022, medical records, symptoms, diagnostic process, distribution between subtypes, and treatment plans, with safety and efficacy results, were assessed. Results: A total of 152 patients with localized disease were included (43.4% R, 21.0% BR, 33.6% LAU). The population characteristics exemplified differences between daily practice and clinical trials. Tumor location and symptoms were as expected. Treatment plan was conditioned by PS or comorbidities in 23.0% of patients. In patients with R disease, surgery followed by different adjuvant chemotherapy (CT) regimes was the antineoplastic treatment of choice (64.8%) with efficacy results (OS 37.5 months;95% CI 18.4 - 56.7), in the range of contemporary standards. The common use of neoadjuvant CT for BR disease (94.4%), with surgery in 50% of them, and its results (OS 30.8 months;95% CI 10.5 - 51.2) reflected current controversies of treatment recommendations and evolution in this scenario. Paliative CT with or without radiotherapy was the standard specific treatment in LAU disease (95.1%) with survival results (PFS: 10.8 months;95% CI 8.8 - 12.7. OS: 20.3 months;95% CI 13.5 - 27.2) that justify the distinct character and the specific study of this entity. Conclusion: RWE for localized pancreatic cancer aroused from the analysis of this population confirms the distinct nature of patients assisted in daily practice, as well as mirrors the complexity of decision making in clinical assumptions in which achieving stronger evidence should be paramount.

Different strategies of treatment for uterine cervical carcinoma stage ⅠB2-ⅡB

Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.

Role of MGMT as biomarker in colorectal cancer

O6-methylguanine DNA methyltransferase(MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients.

Biological subtypes of breast cancer: Prognostic and therapeutic implications

Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.

Treatment of esophagogastric junction carcinoma:An unsolved debate

The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening programs to individuate and eradicate BE represent the best way to reduce AEG cancer. Several endoscopic approaches are here discussed. Surgicalstrategies for different types of AEG cancer are now fairly standardized, and multidisciplinary strategies u s i n g c h e m o t h e ra py o r c h e m o ra d i o t h e ra py m ay improve the outcome of these patients. Here we briefly discuss the keypoints, main topics, and critical issues, according to accumulating evidence and taking into account our own experience.

Comparison of Effectiveness of Gefitinib, Erlotinib, and Afatinib in Advanced Non-small Cell Lung Cancer Patients with EGFR Mutation Positive in Indonesian Population

Background and objective EGFR-tyrosine kinase inhibitors(EGFR-TKIs) were used to treat non-small cell lung cancer(NSCLC) patients with EGFR mutation positive. This study aims to compare the effectiveness of first line TKIs;gefitinib, erlotinib, and afatinib in the treatment of advanced stage NSCLC patients with EGFR mutation positive in the Indonesian population.Methods A retrospective cohort study of 88 NSCLC patients with EGFR mutation positive treated with gefitinib(n=59), erlotinib(n=22), and afatinib(n=7) was performed in national cancer hospital in Indonesia.Inclusion criteria were stage IIIb or IV NSCLC with adenocarcinoma subtype. Subjects less than 18 years or with a history of other malignancy were excluded. Outcomes were treatment response, progression-free survival(PFS), and mortality rate. Results Complete response, partial response, and stable disease were shown in 1.1%, 35.2%, and 31.8% of subjects, respectively. There were 31.8% of subjects developed progressive disease during treatment. Regarding EGFR mutation positive profile, a total of 56.8% subjects had deletion in exon 19, 42% subjects had mutation in exon 21, and rare mutation in exon 18 was found in 3.4% of total subjects. Demography and clinical characteristics had no significant association with the risk of progressive disease. The median PFS of subjects was 11 months(95%CI: 6.8-15.2 months). There was no statistical difference of PFS between treatment groups.Conclusion Gefitinib, erlotinib, and afatinib have similar effectiveness in advanced stage NSCLC with EGFR mutation positive. Afatinib tends to be associated with longer PFS but further investigation is required.