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.

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.

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.

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.

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.

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.

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.

Non-exercise estimated cardiorespiratory fitness and cancer incidence:The NIH-AARP diet and health study

Background Non-exercise estimated cardiorespiratory fitness(NEE-CRF)has been shown to be associated with mortality,although its association with cancer incidence is unknown.The study aimed to assess the prospective association between NEE-CRF and cancer incidence in a large cohort of men and women.Methods The National Institutes of Health-American Association of Retired Persons diet and health study is a prospective cohort that included 402,548 participants aged 50–71 years who were free from cancer at baseline(1995–1996)(men(n=238,835)and women(n=163,713))and were followed until December 31,2015.The exposure variable was NEE-CRF expressed in metabolic equivalents.NEE-CRF was estimated using a validated equation of self-reported predictors on demographics and lifestyle behaviors derived from baseline questionnaires.Primary outcomes were total cancer incidence and incidence of prostate,breast,lung,and colorectal cancers.Cox proportional hazards models were analyzed for the association between NEE-CRF and cancer incidence outcomes adjusted for established cancer risk factors.Results During 13.7±3.2 years of follow-up(mean±SD),64,344 men and 31,315 women developed a new cancer.For every 1-metabolic equivalent higher NEE-CRF,the hazard ratios and 95%confidence intervals(95%CIs)were 0.96(95%CI:0.94–0.97)and 0.88(95%CI:0.84–0.92)of total and colorectal cancer incidence among men,and 0.95(95%CI:0.93–0.97)and 0.94(95%CI:0.91–0.97)of total and breast cancer incidence among women,respectively(all p<0.001).NEE-CRF was not associated with incidence of prostate and lung cancers in men or colorectal and lung cancers in women.Conclusion These results suggest that higher CRF levels,as assessed by the applied non-exercise estimated method,may provide preventive benefits against the development of cancer,while low CRF could potentially serve as a modifiable cancer risk factor.Integrating NEE-CRF into screening paradigms and referring low-fit individuals to improve CRF could complement the public health prevention strategy against cancer.

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.

Treatment strategies for patients with HER2-positive gastric cancer

Gastric cancer (GC) is a major health concern globally,ranking fifth in frequency and fourth in cancer-associated mortality1.In China,an estimated 396,500 new cases are diagnosed each year,and late-stage disease comprises more than 80%of cases2.Because of late diagnosis and heterogeneous characteristics,the prognosis of GC remains poor.For patients with advanced disease,traditional chemotherapy has been the mainstay of treatment,but its clinical outcomes are far from satisfactory,with a 5-year survival rate below 10%.

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.

Sunitinib-induced hyperammonemic encephalopathy in metastatic gastrointestinal stromal tumors:A case report

BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use.Here,we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.CASE SUMMARY A 66-year-old male with metastatic GIST was admitted because of reduced consciousness.Imatinib was administered as the first-line systemic therapy.He experienced repeated episodes of peritonitis due to tumor perforation,and surgery was performed.Progressive disease was confirmed based on increased liver metastasis,and sunitinib was initiated as a salvage treatment.However,23 d after the third course of sunitinib,he presented to the emergency room with an episode of altered consciousness and behavioral changes.Based on the patient clinical history and examination findings,sunitinib-induced encephalopathy was suspected.Sunitinib was discontinued,and the patient was treated for hyperammonemia.The patient had a normal level of consciousness four days later,and the serum ammonia level gradually decreased.No further neurological symptoms were reported in subsequent follow-ups.CONCLUSION TKI-induced hyperammonemic encephalopathy is potentially life-threatening.Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.

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.

Speztler-Martin补充分级法在脑动静脉畸形的临床应用

目的评价Spetzler-Martin补充分级法是否能更好地筛选手术患者、提高术后预判的准确性。方法回顾性分析我院手术治疗的221例脑动静脉畸形,记录改良Rankin量表评分以及相关临床、影像学资料。建立两种不同Logistic模型,比较不同模型的ROC(receiver operating characteristic curve)曲线下面积并进行统计学分析。结果 Spetzler-Martin补充分级模型ROC曲线下面积(0.901),Spetzler-Martin评分系统模型ROC曲线下面积为(0.774),两者间的差异有统计学意义(P=0.0362)。结论 Spetzler-Martin补充分级法能有效地进一步把患者根据手术风险进行细化分组,更加准确地评估手术风险。当Spetzler-Martin补充分级小于或者等于5分时(敏感性:70%,特异性:88.24%),患者手术风险较低,可以作为是否手术治疗的一个重要参考依据。

抗氧化蛋白Prx1在口腔黏膜白斑中的表达

目的检测抗氧化蛋白Prx1和DNA氧化损伤标记物8-OHdG在口腔黏膜白斑中的表达,探讨Prx1在口腔黏膜白斑中的作用。方法选择40例口腔黏膜白斑,包括单纯增生10例,白斑伴上皮轻度异常增生15例,白斑伴上皮中度异常增生15例,正常口腔黏膜10例。采用免疫组织化学染色方法,分别检测Prx1、8-OHdG在黏膜中的表达。结果口腔黏膜白斑伴上皮中度异常增生组Prx1和8-OHdG染色的MOD值均高于正常组、白斑单纯增生组、白斑伴上皮轻度异常增生组,且差异有统计学意义(P<0.01)。结论 Prx1与口腔黏膜白斑的发病有关,口腔黏膜白斑的发生可能与氧化损伤有关。