[The liquid biopsies: What is their contribution to the management of cancer?] / Les biopsies liquides : quel est leur apport en oncologie ?

The « liquid biopsies ¼ are samples of liquids such as blood, urine, spinal fluid that can contain tumor material. Clinical assays have been mainly focused on the peripheral blood containing circulating tumor cells and circulating tumor DNA. The circulating tumor cells are cancer cells released from the primary tumor or recurrences or metastases. They enter into the bloodstream after passing through the vessel wall. It is possible to analyze the circulating tumor cells by means of all cytologic and biomolecular techniques. The free circulating tumor DNA is made of fragments of DNA released by living or necrotic tumor cells proceeded from any place of the organism. The free circulating tumor DNA and DNA from circulating tumor cells show structural rearrangements among which some are therapeutic targets. Many studies showed that circulating tumor cells and circulating tumor DNA analyses are useful in revealing recurrences and tracking therapeutic targets.

Eosinophilic Esophagitis in Children: Endoscopic Findings at Diagnosis and Post-intervention.

PURPOSE OF REVIEW: The goal of this review is to present and summarize studies on endoscopic findings in eosinophilic esophagitis (EoE), at diagnosis and in response to treatment, utilizing rigorous peer-reviewed literature in children wherever possible and to introduce a recently proposed standardized endoscopic evaluation system. RECENT FINDINGS: Gold standard of diagnosis and assessment of response to therapy in EoE requires multiple endoscopies with biopsies for histology, which allows for observation of the esophageal mucosa. Typical endoscopic findings in patients with EoE include edema, exudate, furrowing, concentric rings, and strictures. Endoscopic findings have been broadly characterized into inflammatory features (edema, exudate, furrowing) and fibro-stenotic features (rings, stricture), in order to better reflect their underlying pathophysiology. Recent studies suggest strong correlations between endoscopic findings, through composite scoring systems, and histology, and therefore may be helpful as part of disease surveillance. The EoE Endoscopic Reference Score (EREFS) classification system was proposed in 2013 as an outcome metric for standardization in reporting endoscopic signs of EoE. Subsequent studies support utility of composite scoring, which utility has similarly been seen in pediatric treatment trials. Endoscopy in children provides insight into the natural history of EoE, with progressively more fibro-stenotic features occurring over time, giving an additional perspective into esophageal remodeling and response to treatment. Recognition of typical endoscopic findings at diagnosis and upon repeat endoscopy has allowed a clinician to monitor visual changes in esophageal mucosal health. Further studies to assess the role of composite scoring in disease management are needed.

Association of the postoperative white blood cells (WBC) count in peripheral blood after radical surgical treatment of left upper lobe non-small cell lung cancer (NSCLC) with overall survival - single center results.

INTRODUCTION: The individual patient prognosis after radical surgery for Non-small cell lung cancer (NSCLC) of left upper lobe remains still unclear. The purpose of this study is to evaluate the predictive value of elevated white blood cell count in peripheral blood as early indicator of postoperative NSCLC prognosis. METHODS: A retrospective statistical analysis was performed studying patients subject to radical treatment of left upper lobe NSCLC in period of five years with subsequent one to three-year monitoring of morbidity and mortality of the patient population. The statistical ROC (Receiver Operating Characteristic) analysis of the WBC count in peripheral blood third day after the operation was used to evaluate the relationship with overall survival, with respect to patients surviving for at least 24 months. RESULTS: Based on the results of the ROC analysis with a total area under the curve (AUC) of 0.67, it is possible to confirm that the WBC count established third day after the operation allows us to classify patients into groups according to the 24-month overall survival. CONCLUSION: Our findings confirm the potential of using WBC count to improve current protocols to establish postoperative prognosis for NSCLC of the upper left lobe (Tab. 2, Fig. 1, Ref. 11).

Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group.

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.

Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study.

BACKGROUND: The histopathological features of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome remain poorly characterized. OBJECTIVES: To better characterize the histopathological features of DRESS syndrome, and define the phenotype of the effector cells in the skin and compare it with maculopapular rash (MPR). METHODS: We conducted a retrospective study on 50 skin biopsies from patients with DRESS syndrome (n = 36). Histopathological and immunophenotypical features were studied and compared with a series of MPRs (n = 20). RESULTS: Foci of interface dermatitis, involving cutaneous adnexae, were frequently seen in cases of DRESS. Eosinophils were seen in only 20% of cases and neutrophils in 42%. Eczematous (40%), interface dermatitis (74%), acute generalized exanthematic pustulosis-like (20%) and erythema multiforme-like (24%) patterns were observed. The association of two or three of these patterns in a single biopsy was significantly more frequent in cases of DRESS than in a series of nondrug-induced dermatoses (P < 0.01), and appeared to be more marked in DRESS syndrome with severe cutaneous lesions (P = 0.01) than in less severe cases of DRESS and MPR. A higher proportion of CD8(+) and granzyme B(+) lymphocytes was observed in cases of DRESS with severe cutaneous eruptions (erythroderma and/or bullae). Atypical lymphocytes were found in 28% of biopsies, and expressed CD8 in most cases; a cutaneous T-cell clone was rarely found (6%). CONCLUSIONS: The histopathology of DRESS syndrome highlights various associated inflammatory patterns in a single biopsy. Cutaneous effector lymphocytes comprise a high proportion of polyclonal CD8(+) granzyme B(+) T lymphocytes.

[Metachronous lung metastases of mammary carcinoma, or dual malignancy? a surgeons and oncologists point of view case report]. / Metachronní plicní metastázy mamárního karcinomu nebo duplexní malignita? Pohled chirurga a onkologa kazuistika.

Synchronous and metachronous metastases significantly diminish the possibility of remission from cancer. Therefore, therapy needs to be highly effective and strictly individualised. The authors present a case report of a female patient after radical mastectomy due to breast cancer with incidental detection of peripheral lung carcinoid. The aim of the case report is to inform about current trends in primary lung carcinoid therapy through a surgeons and oncologists point of view.

[Polydipsia, increasing fatigue and a huge mediastinal tumor in a 49-year-old woman]. / Polydipsie, zunehmende Müdigkeit und große mediastinale Raumforderung bei einer 49-jährigen Patientin.

A 49-year-old woman presented with unspecific symptoms including polydipsia, increasing fatigue for several weeks, and vague abdominal pain. Serum calcium (5.30 mmol/l; normal range 2.00-2.60) and parathyroid hormone levels (> 2500.0 ng/l; normal range 15.0-68.0) were extremely elevated. Imaging studies showed a huge mediastinal tumor. Based on these findings a hypercalcemic crisis caused by primary hyperparathyroidism was diagnosed. After intensive care treatment and further diagnostic procedures, the patient's parathyroid adenoma was removed by parathyroidectomy. The postoperative course was uneventful.

Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients.

BACKGROUND: BRAF inhibitors are being developed for the treatment of metastatic melanoma harboring a V600E mutation. The use of vemurafenib significantly increases progression-free survival (PFS) and overall survival (OS) in this population of patients, but is associated with numerous adverse skin reactions. PATIENTS AND METHODS: We carried out a systematic dermatologic study of 42 patients treated with vemurafenib. We collected detailed dermatologic symptoms, photos and biopsy specimens of the skin lesions which enabled us to classify the side-effects. The management and evolution of the skin symptoms are also reported. RESULTS: All patients presented with at least one adverse skin reaction. The most common cutaneous side-effects consisted in verrucous papillomas (79%) and hand-foot skin reaction (60%). Other common cutaneous toxic effects were a diffuse hyperkeratotic perifollicular rash (55%), photosensitivity (52%) and alopecia (45%). Epidermoid cysts (33%) and eruptive nevi (10%) were also observed. Keratoacanthomas (KA) and squamous cell carcinoma (SCC) occurred in 14% and 26% of the patients, respectively. CONCLUSIONS: These cutaneous side-effects are cause of concern due to their intrinsic potential for malignancy or because of their impact on patients' quality of life. Management of this skin toxicity relies on symptomatic measures and sun photoprotection.

[Severe necrotizing myopathy subsequent to Merkel cell carcinoma]. / Myopathie nécrosante sévère consécutive à un carcinome à cellules de Merkel.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumour with a poor prognosis. Rare cases of paraneoplastic neurological syndrome have been associated with this type of tumour, namely myasthenic syndrome of Lambert-Eaton and encephalomyelitis. We report the first case of severe necrotizing myopathy with anti-Hu antibodies complicating MCC. CASE REPORT: We describe the case of a 58-year-old woman with Merkel cell carcinoma (MCC) of the forearm complicated by severe necrotizing myopathy associated with the presence of anti-Hu antibodies. This myopathy occurred 3 months after complete remission of MCC. The patient was treated with high-dose corticosteroids combined with two intravenous infusions of immunoglobulins. Her neurological status deteriorated despite this treatment. Pararaneoplastic syndrome (anti-Hu antibodies, necrotizing myopathy) complicating MCC was suspected. There was no visible tumour relapse. After multidisciplinary discussion, it was decided to supplement treatment with chemotherapy (carboplatin and VP-16). The patient died 20 days after the first course of chemotherapy. DISCUSSION: Severe necrotizing myopathy with anti-Hu antibodies may be added to the list of possible paraneoplastic syndromes associated with Merkel cell carcinoma.

[Rare tumors of the gallbladder and bile ducts. A case review]. / Vzácné tumory zlucníku a zlucových cest. Kazuistika.

The authors deal with the problem of benigh tumours of the bile duct which might occur as a very suprising intraoperative finding instead of preoperatively diagnosed "gallstones". This situation can happen because of possible mistakes that might accompany today's modern practical investigative techniques. The presented report is an example of the pre-operatirely assumed choledocholithiasis which was not confirmed during the operation. Instead a rare bile duct tumour was found.

[Wells' cellulitis and bacterial necrotizing cellulitis induced by anakinra]. / Cellulite de Wells et dermohypodermite bactérienne nécrosante induites par l'anakinra.

BACKGROUND: Anakinra is a recombinant form of the naturally occurring human interleukin-1 receptor antagonist. It is used in the treatment of rheumatoid arthritis. The most frequent side effects are injection site reactions, which seem to have a toxic mechanism. PATIENTS AND METHODS: We report two unusual cases of injection site reactions with anakinra: a woman presented Wells' cellulitis of the thigh and a man developed serious bacterial cellulitis distinguished by deep necrosis at the site of the latest anakinra subcutaneous injection. DISCUSSION: The cases are examples of serious side effects that can occur during treatment with anakinra and underline the need for careful use of this new biological agent.

[Robotic procedures in the colorectal surgery]. / Robotické výkony v kolorektální chirurgii.

PURPOSE: The da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA) was developed specifically to compensate the technical limitations of laparoscopic instruments, such as two-dimensional vision, misalignment of hands and instruments, limited dexterity of instruments inside the patient, and fixed instrument tips. The da Vinci system provides a stable camera platform, three-dimensional imaging, excellent ergonomics, tremor elimination, ambidextrous capability, motion scaling, and instruments with multiple degrees of freedom. METHODS: These advantages can be applied in the field of colorectal surgery, and that's why we are reporting 45 cases that underwent robotic colorectal surgery. We concluded that the da Vinci system may be useful in surgical procedures, such as splenic flexure takedown, dissection of the inferior mesenteric artery with identification of the nervous plexus, and dissection of a narrow pelvis. The major drawbacks of robotic systems are high cost, and a lack of tactile sensation and tensile feedback to the surgeon, who must depend on visual cues to estimate the tension exerted on tissue by the robotic arms. RESULTS: In conclusion, robotic colorectal surgery can be performed safely and effectively, using the da Vinci surgical system, because this system has more dexterity and flexibility than conventional laparoscopic instruments. However, prospective randomized studies are necessary to evaluate the preservation of sexual and voiding function, as well as the oncological and functional (pelvic floor disorders) outcomes of this approach.

Histopathologically dysplastic neurofibromas in neurofibromatosis 1: diagnostic criteria, prevalence and clinical significance.

BACKGROUND: Malignant peripheral nerve sheath tumours (MPNSTs) correspond to the most frequent and aggressive neoplasic complications associated with poor prognosis in neurofibromatosis 1. OBJECTIVES: To define the dysplastic neurofibroma potentially at risk of transformation and evaluate its prevalence and incidence. METHODS: According to our database, we retrospectively included, between 1 March 2000 and 31 August 2004, all patients who had subcutaneous and/or plexiform neurofibromas removed surgically. Tumour specimens were systematically reviewed; dysplastic neurofibroma was defined by the association of high cellularity and the presence of atypical cells. Clinically atypical and histopathologically dysplastic neurofibromas were analysed using Fisher's exact test. In addition, three high-grade MPNSTs were analysed retrospectively for the presence of associated histopathologically dysplastic neurofibroma. RESULTS: Among the 89 plexiform and/or subcutaneous neurofibromas surgically removed, high cellularity and cytonuclear atypia were observed in 19% and 17% of cases, respectively. Both criteria were associated in 8.9% of cases (n=8); Mib-1 immunostaining was negative in all cases (n=7). In univariate analysis, only neurological symptoms were significantly associated with dysplasia (P=0.02). Interestingly, dysplastic neurofibroma areas could be identified within or at the periphery of two MPNSTs. CONCLUSIONS: The association of hypercellularity and cytonuclear atypia could be considered as a potential histological prognostic factor of transformation leading to increased surveillance.

[Lymphedema as a complication of hidradenitis suppurativa in three patients]. / Lymphoedème compliquant une hidradénite suppurée: trois observations.

BACKGROUND: We report three patients (respectively 36, 52 and 52 years old) with a long history of hidradenitis suppurativa associated with pubic lymph oedema. CASE REPORT: Dramatic pubic oedema was noted, with "rugby-ball and bag-like" tumefaction associated with nodules and fistula. There was no evidence of lymph node involvement or abdominal lymphatic blockade. One patient underwent surgical excision combined with split-thickness graft and complete healing ensued. Pathological examination of the excised tissue showed telangiectasia and fibrosis. DISCUSSION: Chronic lymphedema affects patients with severe and long-lasting disease. The complication is caused by chronic and recurrent inflammation due to HS with subsequent blockade or destruction of local lymph drainage routes. Once this complication appears, no medical treatment is effective.

[Syringotropic and pilotropic cutaneous T-cell lymphoma without follicular mucinosis]. / Mycosis fongoïde syringotrope et pilotrope sans mucinose folliculaire.

BACKGROUND: Mycosis fongoides rarely exhibits predilection for infiltration of hair follicles and eccrine glands. We report the case of a patient with cutaneous T-cell lymphoma with syringotropism and pilotropism without follicular mucinosis. CASE REPORT: A 51-year-old man presented with erythematous infiltrated patches with alopecia and anhydrosis, cystic lesions, comedon-like lesions, follicular keratosis and an ulcer over the lower left leg. Clinical examination revealed no palpable adenopathy or hepatosplenomegaly. The patient complained about hypohydrosis. Histological examination of skin biopsies evidenced pilotropic cutaneous T-cell lymphoma without follicular mucinosis. Immunohistological examination and T-cell receptor B-chain gene rearrangement analysis showed a clonal population of T-cells. Moreover sweat glands and sweat ducts were infiltrated by atypical lymphocytes with syringolymphoid hyperplasia. DISCUSSION: Syringolymphoid hyperplasia and folliculotropism without follicular mucinosis are rarely seen in mycosis fongoides. Deep biopsies of adnexal structures are required for this critical diagnosis and clonal rearrangement of TCR genes is a reliable means of assessing clonality. Syringolymphoid hyperplasia and pilotropism without mucinosis are variants of cutaneous T-cell lymphomas.

[Severe necrotic and haemorrhagic edema of the upper limbs revealing remitting seronegative symmetrical synovitis with pitting edema]. / Rhumatisme inflammatoire de type RS3PE révélé par un oedème nécrotique et hémorragique grave des membres supérieurs.

BACKGROUND: RS3PE (Remitting Seronegative Symmetrical Synovitis with Pitting Edema) syndrome is characterized by bilateral and symmetrical tenosynovitis of the distal extremities. It occurs with acute onset in older patients aged over 50 years. This heterogeneous entity can be isolated or can reveal various rheumatic diseases and neoplastic conditions. We report a case of RS3PE syndrome associated with unusually severe cutaneous necrotic and haemorrhagic lesions, and revealing malignant monoclonal IgM proliferation. CASE REPORT: A 62-year-old man was admitted for acute and symmetrical synovitis of both hands and forearms associated with fever and increased acute phase reactants. Severe necrotic and haemorrhagic edema developed simultaneously. Laboratory tests ruled out infectious disease and collagen vascular disorder. Clinical symptoms responded promptly to corticosteroids to reveal severe erosive arthropathy of both wrists. The monoclonal IgM proliferation discovered during the acute phase evolved into a malignant medullary plasmocytosis. After adequate treatment of this proliferation, no haematological, cutaneous or articular relapse occurred during the two-year follow-up period. DISCUSSION: This type of cutaneous symptoms has never been reported during the course of RS3PE syndrome. It may be supposed that the severity of the initial clinical picture was linked in this patient to the paraneoplastic nature of this.