Genetic landscape of indolent and aggressive Kaposi sarcomas.

BACKGROUND: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown. OBJECTIVES: To explore the tumour mutational burden in indolent and aggressive KS. METHODS: We performed whole-exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. RESULTS: Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive tumours had at least three deleterious mutations, whereas most indolent tumours harboured only one or no predicted deleterious mutations. Deleterious mutations listed in the Cancer Gene Census were detected exclusively in patients with aggressive disease. An analysis of somatic copy-number alterations (SCNA) revealed a tendency towards higher number of alterations in aggressive KS. CONCLUSIONS: These data suggest that SCNA alterations and an increase in mutational burden promote aggressive KS and that it might be more appropriate to consider indolent KS as an opportunistic skin disease rather than a cancer.

Efficacy and safety of Aethoxysklerol® (polidocanol) 0.5%, 1% and 3% in comparison with placebo solution for the treatment of varicose veins of the lower extremities in Chinese patients (ESA-China Study).

OBJECTIVES: To assess efficacy and safety of polidocanol (POL) versus placebo in the treatment of C1 and C2 non-saphenous varicose veins in Chinese patients. METHODS: Patients were randomly assigned to POL or placebo. POL 0.5%, 1% and 3% were administered depending on varicose vein type. Response after 12 weeks was defined as Grade 4 or 5 on a digital imaging-based five-point scale (C1 veins) or occlusion and/or absence of reflux >0.5 second (C2 veins). Safety was evaluated with a five-point scale and standard safety assessments. RESULTS: Two hundred and eighty-five patients were treated. POL 0.5%, 1% and 3% were each superior to placebo (P < 0.001); response rates: 87.1% versus 13.6%, 86.4% versus 12.5% and 88.6% versus 4.3%, respectively. Significantly more POL than placebo patients were satisfied/very satisfied with treatment. POL was well tolerated, with mostly symptoms at the injection site reported. CONCLUSIONS: Sclerotherapy with POL 0.5%, 1% and 3% was efficacious and safe in Chinese patients.

Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma.

PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.

Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network.

BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. PATIENTS AND METHODS: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. CONCLUSION: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.

[Molecular targeted therapies in small-cell lung cancer]. / Thérapies moléculaires ciblées dans le cancer du poumon à petites cellules.

Small-cell lung cancers (SCLC) are aggressive malignancies, however, characterized by high primary chemosensitivity. Unfortunately, for the vast majority of patients, relapse is the rule with emergence of secondary resistance mechanisms. In the era of molecular targeted therapies, characterization of a number of molecular abnormalities has encouraged implementation of several clinical trials. This literature review summarizes the various pharmacological approaches used in SCLC to improve survival in localized and extensive forms of the disease. Initial trials with molecular targeted therapies have not been able to improve clinical outcome compared to the standard etoposide-cisplatin chemotherapy regimen in extensive forms. However, new targets continue to be identified and many treatments are currently being assessed, including blockade of angiogenesis, signal transduction, cell cycle or induction of apoptosis.

[Prognosis factors of cholangiocarcinoma: contribution of recent molecular biology tools]. / Facteurs pronostiques des cholangiocarcinomes : apport des données récentes de biologie moléculaire.

Cholangiocarcinoma represents the second most common primary hepatobiliary cancer. Although few patients are candidates for surgery, surgical resection represents the only potential curative option. The prognosis for patients remains poor, despite advances in the understanding of mechanisms involved in carcinogenesis. This review aims to assess clinicopathological factors and biological markers for the ability to predict prognosis. Clinicopathologic factors most often cited are tumor size, lymph node involvement, resecability and surgical margins involvement. Molecular biomarkers have been examined and a number of these, including mdm2, p27, matrix metalloproteinases and vitamin D receptor appear to have prognostic utility. The advent of 'omic'-based profiling offers the potential to assess many different biomarkers at the same time. This 'protein/gene signature' could open the way for developing valid and reproducible predictors of survival based on protein or gene profiles.

[Advances in the treatment of thyroid cancer in the era of molecularly targeted therapies]. / Les progrès dans le traitement des cancers de la thyroïde à l'ère des thérapies ciblées moléculaires.

During last decade, many progresses have been made in the understanding of thyroid cancer molecular biology. This knowledge led to the development of novel targeted therapy in iodine-resistant patients. However, the management of patients remains complex because of the broad spectrum of clinical presentation of thyroid cancers, differences in their natural histories and the lack of data about randomized trials. Angiogenesis inhibitors (sorafenib, motesanib, axitinib and vandetanib) have shown promising activity in differentiated thyroid cancer. Vandetanib, an inhibitor of RET and VEGFR tyrosine-kinases, is promising in medullary thyroid cancers. Preliminary results of these trials are discussed in this review.

Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts?

AIMS: In the era of targeted therapeutics, histological typing of hepatobiliary carcinomas has major clinical implications. Little is known about the reproducibility of the pathological diagnosis of primary liver carcinomas. Therefore, this study aimed to evaluate the worldwide variation in the pathological expert diagnoses of primary liver carcinomas with fibrous stroma in patients who did not have cirrhosis. METHODS: A single set of slides was selected from 25 tumours, and this set was reviewed independently by 12 pathologists who have worldwide expertise in liver tumours. Reproducibility of the diagnoses was evaluated by Light's kappa, and diagnoses were clustered by multidimensional scaling. Immunohistochemistry was performed after histological review. RESULTS: The interobserver reproducibility for diagnosis of hepatocellular carcinoma subtypes and cholangiocarcinomas was poor (kappa 0.23-0.52), even when the experts considered that the diagnosis required no additional stains or clinical information. Interestingly, multidimensional scaling revealed three main clusters of tumours: hepatocellular carcinoma with no other specifications (n = 13), fibrolamellar hepatocellular carcinoma (n = 3) and cholangiocarcinoma (n = 9). Using immunohistochemistry, these histological clusters correlated with expression of anti-hepatocyte and anti-cytokeratin 19 (p<0.001). CONCLUSIONS: The results demonstrate the poor reproducibility among experts of the pathological diagnosis of primary liver carcinomas with fibrous stroma in patients who did not have cirrhosis, and highlight that the systematic use of immunohistochemistry may improve the diagnostic accuracy.

Intramuscular haemangioma of the thigh in a basketball player.

Haemangioma is a common benign soft tissue tumour. Intramuscular haemangiomas may present as a perceived sporting injury. Magnetic resonance imaging is the investigation of choice. Intramuscular haemangioma should be considered in the differential diagnosis of unexplained pain and swelling in a muscle.

The Australian polidocanol (aethoxysklerol) study. Results at 2 years.

BACKGROUND: An ongoing study of the safety and effectiveness of polidocanol by 98 investigators in Australia infecting 16,804 limbs over 2 years. OBJECTIVE: To evaluate the complications of polidocanol and compare its effectiveness and complications with sodium tetradecyl sulphate (STD) and hypertonic saline. METHODS: A single-arm prospective study of polidocanol complications and its effectiveness as a sclerosant was performed. This was compared with each investigator's previous experience with other sclerosing agents. Patients had either varicose veins or venule ectasias and/or spider veins (telangiectasia). A total of 16,804 limbs were injected by 98 investigators. Sclerotherapy was performed with 0.5% or 1% polidocanol for telangiectasias or spider veins, and with 3% polidocanol for varicose veins. The effectiveness of the sclerotherapy and any complications were reported during a 2-year period. RESULTS: There were very few complications reported with polidocanol. There were no reported deaths or anaphylaxis. The investigators with previous experience of other sclerosants considered that the effectiveness of polidocanol was superior to STD (85%) and hypertonic saline (84%). Ninety percent of investigators considered that polidocanol had less frequent complications than STD, and 80% considered that these were less severe. Seventy-four percent considered that polidocanol had fewer side effects than hypertonic saline, and 74% considered that these were less severe. CONCLUSIONS: Polidocanol is an effective sclerosant that has few complications.

Haemodynamic significance of incompetent calf perforating veins.

A total of 149 consecutive unselected patients (221 limbs) who presented with signs and symptoms of chronic venous problems (varicose veins with or without ankle oedema, skin changes and leg ulcers) have been studied by clinical examination, ascending deep to superficial venography, Doppler ultrasound and ambulatory venous pressure measurements. Of the limbs, 180 (82 per cent) had varicose veins without obstruction in the deep veins or reflux in the popliteal or femoral veins while 41 (18 per cent) had deep venous disease. Of the 180 limbs with 'primary' varicose veins 110 (60 per cent) did not have incompetent calf perforating veins (group A) while 70 (40 per cent) did (group B). On the basis of the ambulatory venous pressure after calf muscle exercise and the refilling time, the incompetent calf perforating veins of limbs in group B belonged to three subgroups of different haemodynamic significance. In 20 limbs (30 per cent) they were found to be of no haemodynamic significance, in 25 (35 per cent) of moderate haemodynamic significance and in 25 (35 per cent) of major haemodynamic significance. The last were, on clinical examination, indistinguishable from limbs with deep venous disease although they had patent deep veins with competent popliteal valves.

Number and anatomical distribution of incompetent thigh perforating veins.

Although incompetent thigh perforating veins are considered to be a common cause of recurrence of varicose veins after high saphenous ligation, the number and distribution of such incompetent veins have not been reported. The aim of the study was to determine the number and anatomical distribution of incompetent thigh perforating veins. Sixty-five limbs in 48 patients with varicose veins who were found to have incompetent thigh perforating veins on ascending deep to superficial venography were studied. In 80 per cent of patients one incompetent thigh perforating vein was found and in 20 per cent more than one was found. Concomitant incompetent calf perforating veins were found in 92 per cent of the limbs studied. The incompetent thigh perforating veins were found to occur anywhere in the thigh, from the upper edge of the patella to a few centimetres below the saphenofemoral junction. The majority (71 per cent) were found in the middle third of the thigh. All incompetent thigh perforating veins were communicating with the long saphenous vein, including those in five patients with incomplete stripping. The surgeon should be aware of incompetent thigh perforating veins which may be multiple and occur at any site on the medial aspect of the thigh.

Duplex scanning in the assessment of deep venous incompetence.

A noninvasive method to evaluate deep venous incompetence by duplex scanning is presented. For this test, it was decided to have the patient standing so as to make the test less dependent on the need for patient cooperation and to allow gravity to produce reflux. Results were validated against ambulatory venous pressure measurements. The method described had a sensitivity of 84% and specificity of 88%. Duplex scanning is a useful screening test for detecting the presence and site of incompetence in patients with deep venous disease.

The correlation between carotid plaque ulceration and cerebral infarction seen on CT scan.

The purpose of the study was to determine the association between cerebral infarction seen on CT scan and macroscopic ulceration of atheromatous carotid plaques in patients undergoing carotid endarterectomy. Following carotid endarterectomy in 65 patients, specimens were examined for the presence of ulceration without knowing the result of the preoperative CT brain scan. The 65 patients thus investigated underwent 68 carotid endarterectomies: 36 for a history of transient ischemic attacks (TIAs), 13 for amaurosis fugax, and six for prior strokes; 13 asymptomatic patients had prophylactic carotid endarterectomy prior to coronary bypass. A macroscopic ulcer was present in 42 specimens. Twenty-six (62%) of the patients with ulceration had one or more ipsilateral cerebral infarcts on CT scan. Only two (8%) of the 26 patients without an ulcer had cerebral infarcts. Of the 36 patients who presented with TIAs, 26 (72%) had carotid plaque ulcers and 23 (88%) of these had cerebral infarcts on CT scan also. In contrast, only three of 13 asymptomatic patients had plaque ulcers and only one of these had a cerebral infarct. There is a high incidence of cerebral infarction seen on CT scan in patients presenting with TIAs. These infarcts occur predominantly in patients with ulcerated atheromatous carotid lesions.