Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established. MATERIAL & METHODS: Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed. RESULTS: In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor. CONCLUSION: Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

[Target volumes in cervical lympadenopathies of unknown primary: toward a selective customized approach? On behalf of REFCOR]. / Volumes cibles en radiothérapie des adénopathies cervicales de primitif inconnu : état des lieux et pistes vers une approche sélective raisonnée sous l'égide du Refcor (Réseau d'expertise français des cancers ORL rares).

The treatment of carcinomas of unknown primary revealed by cervical lymphadenopathy is based on neck dissection and nodal and pan-mucosal irradiation to control the neck and avoid the emergence of a metachronous primary. The aim of this review was to assess diagnostic and therapeutic approaches and criteria that may be used for a customized selective approach to avoid severe toxicities of pan-mucosal irradiation. A literature search was performed with the following keywords: cervical lymphadenopathy, unknown primary, upper aerodigestive tract, cancer, radiotherapy, squamous cell carcinoma, variants. The diagnostic workup includes a head and neck scanner or MRI, ((18)F)-FDG PET CT, a panendoscopy and tonsillectomy. Squamous cell carcinoma represents over two thirds of cases. The number of metastatic cervical nodes, nodal level, and histological variant (associated with HPV/EBV status) may determine the primary site origin and might be weighted for the determination of radiation target volumes on a multidisciplinary basis. A selective customized approach is relevant to decrease radiation toxicity only if neck and mucosal control is not impaired. Although no recommendation can yet be made in the absence of sufficient level of evidence, the relevance of systematic pan-mucosal irradiation appears questionable in a number of clinical situations. Accordingly, a customized selective redefinition of target volumes may be discussed and be prospectively evaluated in relation to the therapeutic index obtained.

[An ovarian mucinous borderline tumour with mixed mural nodules]. / Une tumeur ovarienne mucineuse borderline avec des nodules muraux mixtes.

The occurrence of mural nodules in serous or mucinous ovarian tumours is not frequent. Mural nodule can be developed in benign, borderline or malignant tumours. They can be benign, malignant or mixed type. Thus the prognosis of the ovarian tumour can be dramatically modified by the presence if these nodules. Eighty-two cases of mural nodules were reported in the literature, among which we account four cases of mixed nodules type. We report an additional case of mixed type mural nodules of anaplastic carcinoma and sarcoma-like developed in an ovarian mucinous borderline tumour at a 60-year-old woman.We give details about the classification, the differential diagnosis and prognosis of theses nodules.

[Oncogenic osteomalacia: increased production of fibroblast growth factor 23 is not the unique actor]. / Ostéomalacie oncogénique : le FGF 23 ne fait pas tout.

The importance of fibroblast growth factor 23 (FGF 23) has been highlighted in the mechanism of urinary leakage of phosphate in the oncogenic osteomalacia (OO). It is now a component of diagnosis of this disease. We report a 58-year-old man who presented with osteomalacia and hypophosphatemia secondary to urinary leakage of phosphorus. Although serum FGF 23 was normal, the diagnosis of OO was obtained after another cause of acquired prolonged hypophosphatemia has been excluded (hyperparathyroidism and Fanconi syndrome in particular). The search for a deep tumor was performed, allowing the detection of a 12 mm hemangiopericytoma in the upper thigh. Its removal allowed the rapid resolution of clinical symptoms and laboratory abnormalities. The importance of functional sequelae in OO depends on prompt diagnosis. Tumorectomy remains the optimal treatment. Thus, the search for a secreting tumor is essential even in the absence of elevated serum FGF 23.

Mandibular osteosclerotic lesion of a parotid salivary duct carcinoma: demonstration of the neural tropism of these tumors.

INTRODUCTION: Salivary duct carcinoma (SDC) is an uncommon entity of salivary gland cancers with a poor prognosis due to local aggressiveness or distant recurrences involving lymph nodes, lung, and long bones, in which secondary lesions are usually osteolytic. The authors report the first case of mandibular SDC, atypical due to its osteosclerotic presentation and its site, attributed to aggressive neural spread of the tumor along the trigeminal nerve. CASE STUDY: This asymptomatic osteosclerotic bone involvement was diagnosed based on pathological enhancement of the trigeminal nerve demonstrated on MRI and was accompanied by facial nerve involvement up to its third intracranial portion. Radical surgery ensured disease control with continued good quality of life at the 4-year follow-up visit. CONCLUSION: Nerve enhancement on MRI and determination of specific tumor markers (HER-2/neu and p53) should be taken into account to evaluate the prognosis of SDC and to propose appropriate surgical treatment.

[Systemic corticosteroid treatment and risk of infectious diseases]. / Corticothérapie systémique et risque infectieux.

PURPOSE: It was shown that corticosteroids alter the inflammatory and immune responses. Many publications report on serious infections occurring in patients receiving corticosteroids or presenting with Cushing's syndrome. This information is synthesized in this article. CURRENT KNOWLEDGE AND KEY POINTS: The demonstration of the infectious risk associated with corticosteroids relies on observational data and on biological plausibility. However, this risk remains difficult to quantify, because of many confusing factors such as the patients' associated conditions and immunosuppressive treatments, and the highly variable dose and duration of the corticosteroid treatment. Taking into account the published data, the screening for a chronic infection seems licit among patients receiving a systemic corticosteroid treatment, in particular for those who will receive more than 10 mg of prednisone per day. FUTURE PROSPECTS: Although no clinical trials of prevention of infections in corticosteroid treated patients has been published, a strategy aiming at minimizing the infectious risk of corticosteroid treated patients is proposed, based on the analysis of the literature presented in this article.

[Is there an evidence-based management of idiopathic retroperitoneal fibrosis?]. / Peut-on proposer une prise en charge de la fibrose rétropéritonéale idiopathique validée par les données de la littérature?

BACKGROUND: Nowadays it is quite easy to diagnose idiopathic retroperitoneal fibrosis (IRF), particularly with the help of medical imaging. However there is no guideline about the treatment. PURPOSE: Looking for data about an evidence-based management. METHODS: Screening of the database Medline. Titles and abstracts of articles published between 01/01/1985 and 31/12/2004 have been read to identify clinical trials and series about more than ten patients. RESULTS: No record of any therapeutic trials has been found. Eight series in total, which included 177 patients, were identified. Two of the patients have been treated by an ureteral desobstruction only (endoscopy or nephrostomy), 45 by surgery (ureterolysis), 65 by corticotherapy and 64 both by surgery and steroids. For 38 patients, immunosuppressive drugs were combined with corticotherapy (azathioprine, cyclophosphamide or D-penicillamine). According to the authors, doses and duration of corticotherapy varied. Median follow-up lasted 56 months. The outcome is satisfactory in 73% for surgery alone, 86% for medical treatment alone and 73% for both. The association between steroids therapy and immunosuppressive drugs is efficient in 97% of the cases. No clear data about side effects was mentioned. DISCUSSION: Treatment of the IRF is still empirical, based on surgery and corticotherapy. There is no guideline about the treatment strategy. Although tamoxifen has been proposed, efficacy evidence is lacking. Prospective multicenter studies will help us to progress in the management of the IRF.

Clinical significance of tolerant strains of streptococci in adults with infective endocarditis.

OBJECTIVES: To compare the characteristics of patients with endocarditis due to tolerant and non-tolerant Streptococcus strains. PATIENTS AND METHODS: A retrospective nine-year study was conducted in a single tertiary-care hospital. The study included 24 cases of streptococcal endocarditis with known beta-lactam minimal inhibitory and bactericidal concentrations. RESULTS: Ten of the 24 patients concerned were infected with tolerant streptococcal strains, and 14 with non-tolerant strains. Bacterial tolerance was not associated with higher mortality or increased frequency of surgery. Fewer patients infected with tolerant than non-tolerant strains had serum bactericidal titers reaching success-predictive levels, and more of these experienced failure of initial antibiotic treatment and needed longer treatment. CONCLUSIONS: The results of this study strongly suggest that penicillin tolerance of the streptococci responsible for endocarditis has a clinical impact. Consequently, pending a larger prospective study addressing the problem of tolerance, it is clinically relevant to determine the minimal inhibitory and bactericidal penicillin concentrations for all streptococcal isolates causing endocarditis.

[Inverted papilloma: endoscopic versus external surgery. Apropos of 28 cases]. / Papillomes inversés: chirurgie endonasale sous guidage endoscopique versus chirurgie par voie externe. A propos de 28 cas.

To evaluate the role of endoscopic versus external surgery in the treatment of inverted papillomas, the clinical courses of 35 patients over a period of 10 years were reviewed. 13 patients were treated endoscopically whereas 15 were treated with an external approach. 7 patients with a post operative follow up of less than 12 months were excluded from the study. Recurrences occurred in 4 patients, 2 patients had been treated by endoscopic surgery and 2 by medial maxillectomy by lateral rhinotomy. 3 patients were diagnosed with squamous cell carcinoma. Salvage surgery was performed by an external procedure or endoscopically depending on the extension of the recurrence. Late complications occurred in both groups: cosmetic complaints and epiphora were more frequently encountered after external treatment. Functional complaints were noted after endoscopic treatment. If there is no evidence of associated malignancy, if complete exposure of the tumor is possible and long term follow up is feasible, the authors propose endoscopic surgery as first line treatment to excise the body of the tumor, assess it's extension, and remove the root of the tumor. If this is not the case, medial maxillectomy by external approach should be performed.

Prognostic value of MIB-1 antibody labeling index to predict response to Bacillus Calmette-Guérin therapy in a high-risk selected population of patients with stage T1 grade G3 bladder cancer.

PURPOSE: Proliferation rate is an important determinant of bladder tumor progression. However, this factor has not yet been correlated to bacillus Calmette-Guérin (BCG) therapy response in a selected high-risk population of patients with stage T1 grade G3 bladder cancer. To assess the predictive value of the proliferation rate, an immunoreactivity test with monoclonal antibodies MIB-1 was carried out. The aim of this study was to evaluate the prognostic value of an MIB-1 labeling index by selecting a group of responsive patients prior to intravesical therapy. MATERIALS AND METHODS: After complete transurethral resection, 35 patients with T1G3 bladder carcinoma received 6 weekly installations of BCG (intravesical Pasteur strain: 75 mg in 50 ml course of BCG therapy). After treatment a cystoscopy and randomized biopsies of the bladder mucosa were carried out and all recurrences were systematically resected. All tissue samples were fixed in Bouin's solution, embedded in paraffin and stained with hematoxylin-eosin-safran. Pathologists had sufficient material to perform immunomarking in 25 patients using peroxidase-antiperoxidase (PAP) technique, with antiprotein monoclonal antibody MIB-1 (Immunotech, Marseilles, France) to study MIB-1 expression before BCG therapy. Consensus was obtained from three independent pathologists for all sections. The results were expressed in a percentage of marked nuclei. Ten percent increment thresholds were established from 10 to 60%. Contingency tables were established, chi2 (p1) and Fisher exact test (p2) were performed for each threshold of 10%. RESULTS: Median follow-up was 57.3 months (range 25-144). Of the 25 patients, 8 (32%) did not respond to BCG therapy, 17 (68%) responded positively. With a 20% threshold, there was a statistical difference (p1 = 0.03, p2 = 0.04) between responder (R) and nonresponder (NR) patients. All the 7 patients with less than 20% of nuclear activity positively responded to BCG. At this threshold level, sensitivity was high but specificity low (positive predictive value = 0.44). If we consider other reactivity thresholds there were no statistical differences between R and NR patients (10%) threshold p1 = 0.13, p2 = 0.19; 30% p1 and p2 = 0.20; 40% p1 = 0.82, p2 = 0.61; 50% p1 = 0.57, p2 = 0.55). CONCLUSION: Our study indicates that the proliferation rate, assessed by MIB-1 immunoreactivity in Bouin's solution-fixed primary tissue, could be a useful predictive marker of outcome in T1G3 bladder carcinoma. With a 20% reactivity cut-off, a negative MIB-1 immunomarking appears to predict a positive response to BCG instillations. However, on the other hand, MIB-1 is of limited clinical use because the low specificity of this test cannot predict failure and then select candidates for cystectomies.

Human T cell leukemia virus type I expression in salivary glands of infected patients.

Human T cell leukemia virus type I (HTLV-I) sequences were sought in labial salivary glands of patients with HTLV-I-associated myelopathy or tropical spastic paraparesis and of seropositive neurologically healthy carriers. HTLV-I proviral DNA was found by polymerase chain reaction amplification in DNA extracted from lip biopsies of every patient. Viral RNA was found by in situ hybridization in the acini epithelium, as well as in lymphocytic infiltrates. This observation suggests that HTLV-I expression in labial salivary glands could participate in the inflammatory lesions observed in these patients. Some seronegative patients with Sjögren's syndrome or dryness syndrome were also positive for viral transactivator tax DNA (41% in Martinique and 16% in non-HTLV-I-endemic region). Despite histologic signs of lymphocytic infiltration, no viral expression was found in the labial salivary glands of these patients.

[Inflammatory fibroid polyps of the colon]. / Polypes fibro-inflammatoires du côlon.

Inflammatory fibroid polyp is an uncommon lesion involving the stomach, the small bowel and occasionally the colon. Inflammatory fibroid polyp is a large polypoid lesion arising from the submucosa. It has no malignant potential although extensive infiltration may occur. The main histological characteristics are diffuse inflammatory infiltrate with eosinophils and highly vascularized fibrocytic stroma. Immunohistochemistry is always positive for vimentine and negative for S 100 and desmin. We report four cases of inflammatory fibroid polyps, 3 of which mimicked carcinoma of the colon. Exploratory laparotomy and histopathological examination of the resected specimen were necessary to confirm definitive diagnosis. In the last case, diagnosis was established by histological examination of an endoscopically-removed colonic polyp.

Severe valvular heart disease in patients on chronic dialysis. A five-year multicenter French survey.

A retrospective multicenter survey of the 230 chronic dialysis centers in metropolitan France, conducted between January 1 1998 and December 31 1992, to assess the incidence, causes and features of severe valvular heart disease among chronic dialysis patients, identified 98 patients. The annual incidence was estimated to be 15 to 19 cases per 10,000 dialysed patients. The most common etiologies were calcific valvular disease (69%) and endocarditis (19%). Calcific valvular disease led mostly to aortic stenosis, whereas endocarditis primarily caused mitral insufficiency. Two valves were damaged in 32% of the endocarditis patients versus 9% of those with calcific valvular disease. Sixty-one patients underwent surgery. Median overall survival after surgery was 25 +/- 3.0 months. Patients who underwent surgery for calcific valvulopathy, aortic stenosis or only aortic valve replacement had a median survival of 36 months. Patients who underwent surgery for endocarditis or replacement of 2 valves had a median survival of < 12 months. Actuarial survival of surgical patients differed significantly between: i) the patients for whom presurgical evaluation showed a single valvular lesion and those with multiple valvular lesions (p = 0.002), ii) the patients who had surgery to replace a single heart valve and those who had another type of surgery (p = 0.001), and iii) the patients who had surgery to insert a single aortic prosthetic heart valve and those who had another type of surgery (p = 0.004). Multivariate analysis (including etiologies, number of valvular lesions and type of surgery) showed that survival was significantly dependent only on the number of severe valvular lesions (p = 0.002). Five patients with severe calcific aortic stenosis died before scheduled surgery could be performed. These data suggest that, for patients on chronic dialysis, calcific aortic stenosis is the most frequent form of severe valvular disease. Because aortic stenosis progresses rapidly in these patients and thus quickly leads to irreversible cardiac failure, the operative risk, although high in this population, seems acceptable when only one valve is affected.