[New guidelines for stage III melanoma (the French Cutaneous Oncology Group)]. / Actualisation des données concernant le mélanome stade III : nouvelles recommandations du groupe français de cancérologie cutanée.

Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.

[Nodulocystic eruption induced by sorafenib]. / Éruption nodulo-kystique induite par le sorafénib.

INTRODUCTION: Sorafenib is a multikinase inhibitor used in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma, and differentiated thyroid carcinoma. Cutaneous adverse events are numerous and occur frequently. PATIENTS AND METHODS: We present two cases of nodulocystic lesions associated with comedones in patients treated with sorafenib for hepatocellular carcinoma. In the first patient, a 64-year-old man, lesions appeared on the trunk one year after beginning sorafenib. Histopathological examination revealed a non-granulomatous, perivascular and perisudoral polymorphic cellular infiltrate associated with comedones and microcysts. These lesions progressed via inflammatory episodes interrupted by long periods of spontaneous remission without any specific treatment. In the second patient, a 53-year-old woman, a rash appeared on the buttocks three months after starting sorafenib and then spread to the lumbar region and thighs. Histopathological examination was consistent with granulomatous acne lesions. The initial treatment (oral tetracycline and zinc) given for 3 months proved ineffective. Patient follow-up over 3 years showed gradual regression without the appearance of any further lesions. DISCUSSION: In the literature, several reports discuss acneiform rashes in patients treated with targeted therapy. In most cases, these lesions were papulopustular without retentional lesions. There are few reports of nodulocystic eruptions associated with comedones following sorafenib therapy. The mechanisms of emergence of these lesions seem to involve inhibition of the RAF pathway, C-KIT, and the PDGF signaling pathway.

[Limbic encephalitis: a new paraneoplastic auto-immune manifestation associated with metastatic melanoma?]. / Encéphalite limbique : une nouvelle manifestation auto-immune paranéoplasique associée au mélanome métastatique ?

BACKGROUND: Several studies indicate an association between immune-related manifestations and prolonged survival in metastatic melanoma. Limbic encephalitis driven by immune-mediated disorders may also be observed during the course of certain cancers. PATIENTS AND METHODS: In November 2009, a 60-year-old woman followed up for metastatic melanoma since July 2005 developed rapidly progressive cognitive disorder. Clinical, biological, MRI and electroencephalogram abnormalities resulted in diagnosis of probably paraneoplastic limbic encephalitis in a context of immune-related manifestations although chemotoxicity could not be ruled out. Auto-immunity with hypothyroidism and thrombocytopenia were seen concomitantly. DISCUSSION: To the best of our knowledge, this is the first reported case of probably paraneoplastic limbic encephalitis associated with melanoma, a new example of an immune-related condition associated with prolonged survival in metastatic melanoma.

[Merkel cell carcinoma: a new radiation-induced cancer?]. / Carcinome de Merkel : un nouveau cancer radio-induit ?

BACKGROUND: Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine tumour, appears primarily on sun-exposed areas in light-skinned elderly subjects. UV exposure and profound immunosuppression (particularly in a setting of solid organ transplantation, haematological malignancies, HIV) constitute the principal risk factors. The aetiopathogenesis of this cancer is not known, although a polyomavirus involved in the oncogenic process was recently discovered. The carcinogenic effect of ionizing radiation, while not clearly established, has been suspected in rare cases involving the onset of MCC in irradiated zones. We report a new case of case of MCC in a patient previously undergoing radiotherapy. CASE REPORT: A 59-year-old-man underwent radiotherapy for a Darier-Ferrand dermatofibrosarcoma on the left shoulder and developed MCC at the same site 38 years later. DISCUSSION: The time between radiotherapy and diagnosis of MCC, its site within the radiation field (radio-dermatitis), the description of similar cases in the literature concerning the onset of MCC in irradiated areas, and the known carcinogenic effects of ionizing radiation all militate strongly in favour of the radiation-induced nature of MCC.

[Detection of melanoma relapse: a retrospective study of 100 patients]. / Modalités de diagnostic des récidives de mélanome: étude rétrospective chez 100 malades.

BACKGROUND: There is no international consensus on practical methods of monitoring melanoma following surgical removal of a primary tumour. The chief aim of such monitoring is to ensure detection of relapse where early diagnosis is crucial for survival (i.e. in-transit and lymph node metastases amenable to surgical removal) and the emergence of any first recurrence of primary melanoma. AIM: The aim of our study was to identify the role of various agents and diagnostic tools both in first recurrence of primary melanoma and in clinical relapse of melanoma. PATIENTS AND METHODS: This was a retrospective study covering all patients with in-transit or regional lymph node metastasis seen between January 2005 and December 2007. The type of recurrence and method of detection were studied. RESULTS: Ninety-four patients presented recurrence, with 66% of relapses comprising regional lymph node metastasis and 34% consisting of in-transit metastases. Thirty-three percent of cases of recurrence were detected by patients themselves, 21% by our department, 22% by a private dermatologist, 18% by a radiologist and 6% by a general practitioner. Fifty-four percent of recurrences among patients aged under 50 years were self-detected compared to 18% among patients aged over 70 years. A second melanoma was detected in six patients. DISCUSSION: This study underscores the great importance of self-examination in melanoma follow-up with over one third of recurrences being self-detected by patients. Self-examination was more effective for younger patients, emphasizing the need to increase awareness among older patients. This study also demonstrates the essential part played by dermatologists in terms of regular follow-up of melanoma.

[Reprint of: New guidelines for stage III melanoma (the French Cutaneous Oncology Group)]. / Republication de : Actualisation des données concernant le mélanome stade III : nouvelles recommandations du groupe français de cancérologie cutanée.

Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.

Myomectomy during pregnancy: uncommon case report.

A case of myomectomy during pregnancy is presented. Generally myomectomy is contraindicated during this period. On the 14th week of pregnancy our patient presented with progressive lower abdominal pain and a tender mass of nearly 12 centimeter diameter in the pouch of Douglas. Therefore an exploratory laparotomy was performed to exclude torsion of an adnexal mass or pedunculated subserous myoma. A dorsal degenerating myoma with short thick pedicle (4 cm diameter) was found. It was compressed between the promontory of the sacrum and the uterus. Myomectomy was performed and pregnancy progressed without complications.

[Hand-foot syndrome and sorafenib]. / Sorafénib et syndrome main-pied.

Sorafenib (Nexavar) is a targeted therapy acting as VEGFR and PDGFR tyrosine-kinase inhibitor that has been approved in France in the treatment of metastatic renal cell carcinoma and hepatocarcinoma. Hand-foot syndrome is one of the more frequent toxicity related to sorafenib. This paper up lights the main points concerning this toxicity in the view of specialists working together in the care of these patients: a pharmacologist, a dermatologist and a medical oncologist. The clinic and symptoms of hand-foot syndrome as the biological interpretation, the symptomatic treatment and the impact on the specific treatment of sorafenib are developed.

Pelvic inflammatory disease due to Streptococcus pneumoniae: a usual pathogen at an unusual place.

We report three cases of pelvic inflammatory disease (PID) due to Streptococcus pneumoniae in previously healthy young women. S. pneumoniae frequently causes bacteremia, meningitis and respiratory infections, but it very rarely infects the genital tract. All our patients presented with an acute onset of severe abdominal pain and had an intrauterine device (IUD) present. No abnormal sexual behavior was noticed. Although the relation between PID due to S. pneumoniae and the use of an IUD has been a topic for discussions, culture of IUD in all our patients and blood culture in 2 of 3 of our patients revealed S. pneumoniae. All patients recovered well with intravenous antibiotic treatment and removal of the IUD.

Impaired bladder emptying in women.

The clinical and urodynamic findings in 1,193 consecutive women referred for investigation of urinary incontinence and other urinary symptoms were reviewed. Impaired bladder emptying was defined as a repeated maximum flow rate below 15 ml/second or a residual urine volume of 150 ml or more. One hundred and sixty-five women were diagnosed as having voiding dysfunction. Fifty-six of the 165 women (34%) had a residual urine volume of 150 ml or more. Voiding dysfunction was the only abnormal urodynamic finding in 27 women and was associated with genuine stress incontinence, detrusor instability or bladder hypersensitivity in a further 138 patients. Overflow incontinence was diagnosed in 7 women (0.5%). Symptoms of impaired bladder emptying were significantly more common in women with proven voiding dysfunction but were absent in a third of these patients. One in 4 women with normal micturition had symptoms of voiding difficulty. Neurological disease, pelvic surgery and psychological factors were important causes of voiding dysfunction. Voiding disorders are a common cause of lower urinary tract dysfunction and should be an important consideration in future patient management.

The significance of polyhydramnios diagnosed during labour or at caesarean section.

In the 38 cases of polyhydramnios reported here the diagnosis was made only at the time of artificial rupture of the membranes to induce or augment labour, or at Caesarean section. Usually this was a benign finding often associated with overweight in the mother (60%) or baby (39.4%). However there was an increased incidence of major congenital abnormality (13.1%) resulting in a high perinatal mortality rate (10.5%); the paediatrician should therefore be alerted prior to delivery of these patients.

Polyhydramnios and associated maternal and fetal complications in singleton pregnancies.

During the 10-year period 1 January 1979 to 31 December 1988, polyhydramnios occurred in 537 patients with singleton pregnancies delivered at the Mercy Maternity Hospital. Associated maternal and fetal complications and the perinatal outcome of these pregnancies with polyhydramnios were analysed. In 248 of the 537 pregnancies (46%) in this group there were no maternal complications or fetal malformations and the perinatal mortality (PNM) rate was 2.4%. The PNM rate increased significantly to 13.1% when there was associated pre-eclampsia, 10% with gestational diabetes, and to 7.6% with miscellaneous complications. When polyhydramnios was associated with a fetal or placental malformation the PNM rate was 61.4%. The commonest malformations were central nervous system (31%), musculoskeletal (12%) and gastrointestinal system anomalies (10%). Placental chorioangioma occurred in two patients (0.4%) and both babies died. In women with low oestriol excretion (18% of the 455 tested) the PNM rate increased five times to 22.7%.

The significance of recurrent polyhydramnios.

A study of 30 women who had polyhydramnios in more than 1 pregnancy revealed that 8 of the 36 resultant pregnancies (22.2%) were associated with diabetes mellitus, 14 (37.8%) with fetal macrosomia, and the perinatal mortality was 16.2% (6 of 37). The incidence of major fetal malformations or abnormalities was 18.9% (7 of 37); 4 of the 6 deaths resulted from malformations (anencephalus (2), hydrocephalus (1), nonimmune hydrops (1)), and the other 2 deaths were from hyaline membrane disease associated with prematurity. Recurrent polyhydramnios occurred in 1 in 1,720 pregnancies. The onset was acute in 3, subacute in 2 and chronic in 31, the perinatal deaths in these categories being 2, 1 and 3 respectively. The risk of recurrent polyhydramnios is the risk of fetal malformation and premature delivery. The latter may be preventable by prompt therapy with indomethacin, and serial amniocentesis if this therapy fails.

Comparison of HMG/HCG superovulation for AID with or without superactive GnRH agonist.

New methods of ovulation induction have been discovered and perfected in recent years. Among others, gonadotrophin-releasing hormone (GnRH) agonists are being used increasingly in the treatment of ovulatory infertility. In a prospective study, 24 women undergoing artificial insemination with donor sperm (AID) and facing failure of treatment because of ovulation disorders, were treated with human menopausal gonadotrophin/human chorionic gonadotrophin (HMG/HCG) superovulation with or without pituitary densensitization using a superactive luteinizing hormone-releasing hormone (LHRH) agonist, buserelin (BUS), Suprefact (Hoechst, Frankfurt a/Main, FRG). In 86 cycles stimulated with HMG/HCG no pregnancy occurred, whereas 12 pregnancies occurred in the same group of patients after a total of 43 BUS/HMG/HCG stimulation cycles. Superactive LHRH agonists have a definite place in the treatment of AID patients presenting with refractory ovulation disorders and/or luteal insufficiency.

Acute and subacute polyhydramnios in singleton pregnancies.

Over a 10-year period when 51,022 singleton infants were delivered, 19 pregnancies (1 in 2,685) were complicated by acute polyhydramnios 17 (1 in 3,000) by subacute polyhydramnios and 501 (1 in 102) by chronic polyhydramnios. The incidence of major congenital malformations in singleton pregnancies associated with acute polyhydramnios was 63% and the perinatal mortality rate was 74%. When subacute polyhydramnios occurred in singleton pregnancies, the incidence of major congenital malformations was 65%, similar to acute polyhydramnios, but the perinatal mortality rate was only 35%. The comparable figures for chronic polyhydramnios in singleton pregnancies were a major malformation incidence of 14% and perinatal mortality rate of 10%. The type of onset of polyhydramnios, acute, subacute or chronic is therefore the most important indicator of prognosis. In patients with gross polyhydramnios, acute renal failure must be specifically excluded.

Acute polyhydramnios in twin pregnancies.

This paper reports the experience with acute polyhydramnios complicating twin pregnancies at the Mercy Maternity Hospital for the 10-year and 2-month period from January, 1979 to February, 1989 during which time there were 13 such cases, an incidence of 1 in 4,044 pregnancies. Acute polyhydramnios complicated 1.7% of all twin pregnancies. The perinatal mortality rate was 88.5% and accounted for 16.7% of the perinatal deaths in twins. No major fetal malformations were found. One case of acute polyhydramnios was successfully managed with ultrasonographically guided serial amniocenteses. The management of this rare condition is considered.

A lesson from IVF endocrinology: the importance of the follicular phase to success and failure in non-IVF cycles.

Sixty-three patients treated with exogenous gonadotropins for a total of 232 non-IVF cycles were monitored by serum E2 and/or total urinary estrogen excretion. The endocrine profile of follicular phase during HMG-HCG stimulation was evaluated with regard to an effect on the pregnancy rate. Six different follicular phase patterns were observed: A-profiles (daily exponential increase of sE2 or total urinary estrogen values followed by a sustained exponential increase on the day after HCG injection) seem to be necessary to obtain pregnancy, being followed by conception in 21.5% of all cases. Other profiles have lower conception rate (10%); no conception occurred when non exponential E2 rise was observed. The different responses are not related to total dosage of HLG administered. Patients who were treated for hypogonadotropic hypogonadism had a high pregnancy rate (80%) even in absence of post-HCG estrogen rise (G-endocrine profiles. Women aged 35 years must have significantly higher doses of gonadotropins to obtain A-profiles. Monitoring by E2 seems to be more adequate than the TUE only (conceptual pregnancy rate/cycle of 15.25%, versus 10.34%). In conception cycle, midluteal E2/P ratio never exceeds 50.

Ureteric obstruction by the gravid uterus.

This paper reports the only 6 cases of ureteric obstruction apparently caused by the gravid uterus diagnosed at the Mercy Maternity Hospital in the past 17 years, during which time there were 82,836 confinements. In 3 of the 6 cases there was clear radiographic evidence that the level of obstruction was at the pelvic brim. The rapid resolution of the ureteric obstruction shortly after delivery strongly suggested that the gravid uterus was the cause of the obstruction. Cases 1-3 were the only patients of 793 with polyhydramnios who developed bilateral ureteric obstruction and acute renal failure. In Cases 4 and 5 there was unilateral ureteric obstruction and pyelonephritis; in Case 4 a ureteric catheter was inserted from below, and in Case 5 a ureteric stent was inserted via a nephrostomy tube. In Case 6 a percutaneous nephrostomy tube was inserted.