Limited applicability and implementation of the international oncology treatments guidelines in low- and middle-income countries, an example from the Mediterranean area borders.

The quality of cancer care in the modern era is based on a precise diagnosis and personalized therapy according to patients and their disease based on validated guidelines with a high level of evidence. During cancer patients' management, the objective is first to make an accurate diagnosis and then offer the best treatment, validated beforehand in a multidisciplinary board meeting, with the best benefit/risk ratio. In the context of many low- and middle-income countries, the limited available means do not allow an adequate offer, resulting in non-optimal patients' care. In addition, in many low- and middle-income countries, priority can be given to other types of disease than cancer, which may considerably reduce allocation of specific resources to cancer care. Thus, the limited availability of systemic therapy, radiotherapy machines, brachytherapy and technological development may come up against another difficulty, that of geographical distribution of the means in the countries or a lack of expertise due to insufficient training programs. For all these reasons, the implementation of the guidelines established in Western countries could be impossible for many low- and middle-income countries which, moreover, have to face a completely different epidemiology of cancers compared to developed countries. In this work, we will discuss through a few examples of common cancers on both borders of the Mediterranean area, the applicability of the guidelines and the limits of their implementation for optimal cancer care.

Economic burden of lung cancer in Morocco: A cost of illness study.

INTRODUCTION: Lung cancer is the most common cancer in men and the second most common cancer in women. It is associated with substantial economic impact in terms of direct and indirect costs. The main objective of this study is to estimate the direct medical cost of lung cancer management in Morocco MATERIALS AND METHODS: A cost-of-illness study was conducted among patients treated at the Mohammed VI Center of Cancer (Casablanca) in 2019. The costs were estimated from the societal perspective using a bottom-up approach. The materials and procedures used were identified and quantified retrospectively from the information system and files. Their monetary value was calculated according to official prices published by the national health insurance agency. The horizon time adopted was 12 months. RESULTS: The study included 271 patients, with an average age of 62.5 ± 9.5 years. Of these, 93.4 % were men and 92.1 % were former smokers. In terms of cancer staging, 68.3 % of patients were in stage IV while 28.8 % were in stage III. Adenocarcinoma was present in 43.5 % of cases. Patients underwent an average of 10.6 ± 5.1 radiological investigations, 56.1 ± 30.9 biological tests, and 24.1 ± 11.7 consultations. The average direct medical cost was 4455.3 USD (95 % CI: 4037.4-4873.2). Chemotherapy accounted for 19.9 % of the total cost, while radiological investigations and drugs accounted for 18.7 % and 17.6 %, respectively. Diagnostic tests and radiotherapy each accounted for 7.6 % of the total cost, while biological tests accounted for 7.5 % and hospitalizations accounted for 7.1 %. The cost was statistically higher in young patients (p = 0.017), in patients with adenocarcinoma (p < 0.0001), in patients with stage II tumor (< 0.00001), in patients who have undergone surgery (p = 0.002), chemotherapy (p < 0.0001), radiotherapy (p < 0.001) and in those without metastases (p < 0.0001). CONCLUSION: These results provide evidence to support the ratification of the Framework Convention on Tobacco Control and the full adherence of the Kingdom of Morocco to the MPOWER measures.

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. / Désescalade thérapeutique dans les cancers de l'oropharynx induit par les HPV : mise au point.

The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.

Metachronous bilateral isolated adrenal metastasis from rectal adenocarcinoma: a case report.

We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients' follow-up for colorectal cancer.

[Granular cell tumor: report of a complicated vulvar localization of pulmonary metastases]. / Tumeur à cellules granuleuses : à propos d'une localisation vulvaire compliquée de métastases pulmonaires.

Granular cell tumour, or Abrikossoff's tumour, is a rare, ubiquitous tumour, with mostly benign evolution. The malignant forms represent 1-3% of the cases. The vulvar localization is exceptional. We report the case of a 28-year-old patient who presented a vulvar Abrikossoff's tumour. Initially considered benign, the tumour was treated by exclusive local surgery. Five months later, the tumour showed a malignant transformation. The tumour size was 14cm in its major axis with the presence of not systematized scattered mitoses, PS 100 was positive at 100% and Ki 67 to 20%. Because of malignant and economic excision of the neoplasm, the patient received adjuvant radiotherapy. After 20 months, the patient had a local recurrence and lung metastasis, supporting the diagnosis of malignancy. She received two chemotherapy regimens of 5-fluoro-uracil/cisplatin and pacliatxel/carboplatin without any response. Following the failure of chemotherapy, the patient received symptomatic medical treatment. This observation leads to advocate an aggressive surgical treatment and strict supervision of all granular cell tumours.

[Bilateral stellate neuroretinitis as presenting sign of pheochromocytoma]. / Neurorétinite stellaire bilatérale révélant un phéochromocytome.

We report the case of a 21-year-old male patient admitted emergently with progressive bilateral severe visual loss for 1 month. Posterior segment examination revealed bilateral stellate neuroretinitis. Infectious serologies were negative, and brain CT was normal. Physical examination was remarkable for malignant hypertension of 220/150 mmHg. Diagnostic work-up revealed a pheochromocytoma documented by histopathological exam upon adrenalectomy. The disc edema and macular exudates resolved once the hypertension was controlled.

[Bilateral sphenoid sinus mucocele presenting as abducens nerve palsy: case report]. / Mucocèle sphénoïdale bilatérale révélée par une paralysie du nerf abducens : à propos d'un cas.

Mucocele is a rare, benign, cystic tumor affecting primarily adults. It arises within the sphenoid sinus and invades the orbit through bony destruction. The most frequent locations are frontal and fronto-ethmoidal; sphenoidal forms are rarer, and bilaterality is exceptionally rare. Ophthalmological signs with the risk of blindness required emergency treatment. The authors report a case of bilateral sphenoid mucocele presenting as an isolated abducens nerve palsy, the etiological investigation confirmed the diagnosis of sphenoid mucocele, and the treatment consisted of a surgical marsupialization through an endonasal endoscopic approach.

[Retrobulbar optic neuropathy secondary to an undifferentiated carcinoma of the sphenoid sinus]. / Neuropathie optique rétrobulbaire révélant un carcinome indifférencié du sinus sphénoïdal.

Undifferentiated carcinoma of the paranasal sinuses is a rare malignant tumor, characterized by rapid growth, local/regional invasion, metastatic potential and poor prognosis despite aggressive treatment. Clinically, this tumor may manifest as episodes of epistaxis, headache or ophthalmic signs, particularly oculomotor nerve palsies, optic atrophy or even proptosis in the case of orbital extension. We report the case of a patient admitted with a left retrobulbar optic neuropathy, which led to a diagnosis of undifferentiated carcinoma of the sphenoid sinus.

[Double prepapillary arterial loop and arterial occlusion]. / Boucle vasculaire prépapillaire bilatérale compliquée d'une occlusion artérielle.

The prepapillary vascular loops are rare congenital vascular anomalies. Often unilateral and asymptomatic, they may be complicated by ischemic events by twisting or thrombosis of the loop. We report a rare case of double prepapillary arterial loop complicated by left retinal ischemia due to thrombosis of the loop.

Molecular detection and genotyping of human papillomavirus in cervical carcinoma biopsies in an area of high incidence of cancer from Moroccan women.

Cervical cancer is a leading cause of cancer-related deaths in developing countries, and the human papillomavirus (HPV) is linked etiologically to cervical cancer. Eighty nine cervical carcinoma biopsies collected from women visiting the Oncologic Center in Casablanca (Centre Hospitalier Universitaire Ibn Rochd, Morocco) for cervical cancer symptoms, were screened for HPV DNA by polymerase chain reaction amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 45, and 59. Using very high stringency hybridization the HPV types could be easily distinguished. After preliminary clinical sorting, 92% (82/89) of the samples were found to be HPV-positive. Among the samples infected by a single HPV, type 16 was the most frequent 36.6% (30/82) of the positive samples, followed by HPV 18; 19.5% (16/82). Double or even multiple infections by the different HPV types were also detected (35.5% of the positive samples); dual infections were the more frequent, with the following combinations of HPVs: HPV16/HPV18 (21% of the positives samples) and HPV16/HPV45 (8.5%).

[Clear cell carcinoma of the parotid gland]. / Carcinome à cellules claires de la glande parotide.

OBJECTIVES: Clear cell carcinomas of the parotid gland are hardly reported only fifty cases are known. They are characterized by a proliferation of acinic epithelial cells and of clear myo epithelial cells. What makes them remarkable is a slow process of evolution. MATERIAL AND METHODS: Three cases which were treated in the Ibn Rochd center of oncology are gathered from the 1999-2003 period into a review in order to discover the epidemic and anatomopathological characteristics of these tumours. The goal of study is to contribute to a best knowledge of the clinical features, pare clinical, anatomopathological and therapeutic characteristic of this tumour. RESULTS: Two men, aged of 62 and 71 and a 82-years-old-woman were concerned. Growing cervical mass was the most revealing symptom. The diagnosis was established by the parotid biopsy in 2 cases and after surgery in the third case. The treatment consisted in a total parotidectomy with conservation of the facial nerve and postoperative radiation at the extend of 65 Gy for the first patient. After 12 months the patient is still alive. As for the two other patients, given the extend of advancement of the tumour, palliative treatment was decided. It resulted in stabilization of the disease and a receding of 22 months for one patient and no trace of the second one because of a loss of the evolutionary pursuit. CONCLUSION: With an in-depth analysis we can notice that clear cell carcinomas of the parotid gland are rare and mostly occur to old patients. Immunohistochemistry is the essential first step to sort these tumour with other salivary ones. Basic treatment is surgery. Radiation therapy linked to surgery seems to improve the local control of the disease. The prognosis remains relatively good despite discusses. Because of the few published cases, it's hard to analyze these tumours.

[Nephroblastoma in adults. Three case reports]. / Le néphroblastome de l'adulte. A propos de trois cas.

The authors report three nephroblastoma's cases occurred in adult and treated at Ibn Rochd Oncology Center at Casablanca. The average of age was 24 years (19-29 years) and the delay of diagnosis was five months (3-8 months). The most frequent clinical sign was a lumbar fossa mass. At diagnosis, radiological exams revealed that patients presented an advanced stage and metastatic disease in one case. The treatment was a total nephrectomy with ganglioma dissection when the tumor was resectable followed by chemotherapy and radiotherapy. Two patients was in progressive disease despite treatment, and one patient was lost at follow-up. The prognosis of adult's nephroblastoma remains very severe, due to the advanced stage at diagnosis and the mediocre reply to the treatment.

[Primitive seminoma of the mediastinum: a case report]. / Séminome primitif du médiastin: à propos d'un cas.

In this study, the case has been reported of a 36-year old male who was treated at the Ibn Rochd Oncology Center in Casablanca for a primary mediastinal seminoma revealed by a symptomatology including cough, dyspnea, laterocervical swelling, rachidial pain and gait disorder. The preliminary investigation showed significant mediastinal enlargement with a right pleuritis and vertebral metastases; tumor markers were normal. The diagnosis of seminoma was confirmed by pathological and immunohistochemical analysis of the cervical adenopathy. Disease management consisted of BEP/cisplatin type chemotherapy and lumbar, mediastinal, and supraclavicular radiotherapy. The response after four courses of combined chemo-/radiotherapy was estimated at 25%, but the patient died from respiratory failure five months after the initiation of treatment.

[Association of fallopian tube cancer and polymyositis. Apropos of 1 case]. / Association d'un carcinome tubaire primitif et polymyosite. A propos d'un cas.

A 51-year-old woman consulted for pelvic pain, metrorrhagia and leukorrhea. Physical examination revealed a renitent and mobile mass in the pelvis. A right lateral uterine mass with hydroxalpinx was found at ultrasonography. Pathology examination of the right annexectomy specimen provided the definitive diagnosis: fallopian tube cancer with polymyositis. No residual tumor was found at total hysterectomy with total bilateral annexectomy. The patient was lost to follow-up for three years without complementary treatment then consulted later for functional disability of the upper then lower limbs with myalgia, swallowing disorders and left supraclavian node enlargement resulting from pelvic relapse of the right fallopian tube adenocarcinoma and left supraclavian metastasis with paraneoplastic polymositis. The patient was given 6 courses of chemotherapy with radiotherapy (45 Gy) centered on the left clavian region. The patient exhibited a spectacular response, and remains in complete remission 50 months after diagnosis. The association of a fallopian tube tumor with polymyositis is exceptional, requiring rapid anticancer treatment effective against the cancer and the paraneoplastic polymyositis.

[Papillary carcinoma from the thyroglossal duct cyst: review of the literature and report of a case]. / Carcinome papillaire sur kyste du tractus thyréoglosse: revue de la littérature et à propos d'un cas.

Cancer of a thyroglossal duct cyst is very rare. Clinical presentation is identical that of a benign cyst, and the diagnosis is histopathological. We report the case of 36 year-old woman treated for papillary carcinoma of a thyroglossal duct cyst. The treatment was surgical excision according Sistrunk method. There was no distant spread. After 22 months follow up, the patient is alive, with no signs of recurrence.

Cytotoxicity and DNA damage associated with pyrazoloacridine in MCF-7 breast cancer cells.

We examined the effects of pyrazoloacridine (PZA), an investigational anticancer agent in clinical trials, on cytotoxicity, DNA synthesis, and DNA damage in MCF-7 human breast carcinoma cells. With PZA concentrations ranging from 0.5 to 50 microM for durations of 3-72 hr, cytotoxicity increased in proportion to the total PZA exposure (concentration x time). Inhibition of DNA and RNA syntheses increased with increasing PZA concentration x time (microM.hr). A 24-hr exposure to 1 and 10 microM PZA reduced DNA synthesis to 62 and 5% of control, respectively, decreased the proportion of cells in S phase with accumulation of cells in G2 + M phase, and inhibited cell growth at 72 hr by 68 and 100%. Newly synthesized DNA was more susceptible to damage during PZA exposure, with subsequent induction of parental DNA damage. Significant damage to newly synthesized DNA as monitored by alkaline elution was evident after a 3-hr exposure to > or = 5 microM PZA. Longer PZA exposures (> or = 10 microM for 16 hr) were required to elicit damage to parental DNA. Induction of single-strand breaks in parental DNA correlated closely with induction of double-strand breaks and detachment of cells from the monolayer. PZA-mediated DNA fragmentation was not accompanied by the generation of oligonucleosomal laddering in MCF-7 cells, but induction of very high molecular weight DNA fragmentation (0.5 to 1 Mb) was detected by pulsed-field gel electrophoresis. In vitro binding of PZA to linear duplex DNA (1 kb DNA ladder) and closed, circular plasmid DNA was demonstrated by a shift in migration during agarose electrophoresis. PZA interfered with topoisomerase I- and II-mediated relaxation of plasmid DNA in a cell-free system, but the cytotoxic effects of PZA did not appear to involve a direct interaction with topoisomerase I or II (stabilization of the topoisomerase I- or II-DNA cleavable complex). PZA-mediated cytotoxicity correlated strongly with inhibition of DNA and RNA syntheses, and damage to both nascent and parental DNA. Neither the cytotoxicity of PZA nor induction of double-stranded DNA fragmentation was prevented by aphidicolin, indicating that PZA-mediated lethality occurred in the absence of DNA replication. Since free radical formation was not detected, induction of nascent and parental DNA damage appeared to be a consequence of the avid binding of PZA to DNA, presumably by interfering with the access of replication, repair, and transcription enzyme complexes.

[Retinal vasculitis]. / Les vascularites retiniennes.

PURPOSE: The purpose of this study is to determine aetiologies of vasculitis of retina in Morocco. MATERIAL AND METHODS: This is a retrospective study on 108 cases of vasculitis of retina admitted in the ophthalmology department, for a 5-year period (1987-1993). Our patients had a complete ophthalmological examination : fluorescine angiography, colour vision, general examination and biological study. RESULTS: Many aetiologies have been found, predominantly Behcet's disease. The neovascularization of retina which complicates the vasculitis was detected in 30 % of our patients. A laser photocoagulation was performed on these cases, sometimes a vitrectomy was necessary when a haemorrhage of vitreous body occurred, complicating the neo-vessels of retina. The therapeutics received by our patients was based on the corticotherapy. An immunosuppression treatment was prescribed in most cases of Behcet's disease and in severe vasculitis. Outcome after treatment has been satisfactory, but many patients relapse very frequently, mainly those with Behcet's disease. CONCLUSION: Causes of vascular retinitis are variable, most of them are due to Behcet's disease.

[Outcome of Behçet disease in ophthalmological milieu in Morocco]. / Devenir de la maladie de Behçet en milieu ophtalmologique marocain.

We treated 123 patients with Behçet's disease during a period of 10 years (1984-1993). The ocular lesions include uveal lesions especially the posterior lesions and vascular retinal. Uveitis was total in 72% of cases. Periphlebitis occurred in 51% of cases, vein occlusion in 10% of cases, macular oedema in 16% and papillary oedema in 10%. Clinical course and prognosis were studied. The functional prognosis is poor as such lesions may lead to blindness, particularly due to papillary oedema maculopathy. The treatment used is based on immunosuppressive and corticoid steroid drugs.

[Outcome of Behçet disease in ophthalmologic practice in Morocco]. / Devenir de la maladie de Behçet en milieu ophtalmologique marocain.

We treated 123 patients with Behçet's disease during a period of 10 years (1984-1993). The ocular lesions include uveal lesions especially the posterior lesions and vascular retinal. Uveitis was total in 72% of cases. Periphlebitis occurred in 51% of cases, vein occlusion in 10% of cases, macular oedema in 16% and papillary oedema in 10%. Clinical course and prognosis were studied. The functional prognosis is poor as such lesions may lead to blindness, particularly due to papillary oedema maculopathy. The treatment used is based on immunosuppressive and corticoid steroid drugs.

Free radical formation by ansamycin benzoquinone in human breast tumor cells: implications for cytotoxicity and resistance.

The benzoquinonoid ansamycin antibiotics, geldanamycin and herbimycin A, are potent cytotoxins against tumor cells in vitro. We have examined the mechanism of their in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells and we have found that multidrug-resistant MCF-7/ADRR cells that exhibit the MDR phenotype and the overexpression of P-170-glycoprotein, were cross-resistant to geldanamycin and herbimycin A. Verapamil, which binds competitively with P-170-glycoprotein, enhanced geldanamycin cytotoxicity 12-fold only in resistant cells, suggesting that geldanamycin may interact with the drug efflux protein. Geldanamycin and herbimycin A, like adriamycin, were reductively activated by the NADPH-cytochrome P450-reductase and formed reactive .OH. The formation of .OH was significantly lower in resistant cells. In contrast to adriamycin, the formation of .OH was unaffected by the addition of DNA, indicating that a DNA-complexed drug was redoxactive and may, therefore, may be more effective in killing tumor cells at the DNA level. These observations indicate that both the decreased free radical formation and interactions with P170 glycoprotein may be important in geldanamycin and herbimycin A resistance in multidrug resistant human breast tumor cells.