Epidermal growth factor receptor tyrosine-kinase inhibitor treatment resistance in non-small cell lung cancer: biological basis and therapeutic strategies.

Lung cancer remains the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents 85 % of all lung cancer cases and it is classified into three major subtypes: adenocarcinoma, squamous cell carcinoma and large-cell carcinoma. In the past years, molecular-targeted therapies have been developed in order to improve response, survival and quality of life in patients with advanced NSCLC. Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine-kinase inhibitors (TKIs). However, virtually all patients with initial response relapse due to acquired resistance. Better understanding the biology of these tumors and mechanisms of EGFR TKIs resistance could shed some light on research of new therapeutic options in this setting. This review aims to emphasize on EGFR involved lung cancer pathway, primary and acquired mechanisms of TKIs resistance, and discuss agents currently used in clinical development in this emerging scenario.

Fine-needle aspiration diagnosis of hydatid cyst.

The diagnosis of hydatid disease outside endemic areas is usually not suspected. Hydatid cysts in imaging studies can be confused with hepatic tumors, abscesses, cystadenomas, liver cysts or other lesions. Serology is the usual confirmatory test, but cytologic diagnosis has been described. Aspiration of the cysts has not been employed as a routine diagnostic method for fear of spillage and anaphylactic reactions. We report a case of unsuspected hepatic echinococcosis that was confirmed by fine-needle aspiration of the lesion and cytologic confirmation without complications.

[Preventive analgesic effect of intraoperative administration of ibuprofen-arginine on postmastectomy pain syndrome]. / Effet analgésique préventif d'une administration périopératoire d'ibuprofène-arginine sur le syndrome douloureux postmastectomie.

The efficacy of preemptive analgesia on postoperative pain is discussed. From experimental neurophysiological data, the present policy of preventive analgesia aims at precluding modifications of the nervous system secondary to a nervous lesion and the appearance of chronic pain, particularly of the neurogenic kind. The post-mastectomy pain syndrome (PMPS) falls within the realm of neurogenic pain and is still poorly understood and underestimated. This study evaluated the preemptive effect of a perioperative administration of an oral non steroid anti-inflammatory, the ibuprofen-arginine, on PMPS. Thirty patients scheduled for partial or total mastectomy with axillary dissection were prospectively and randomly assigned to 2 groups. The ibuprofen-arginine group (group I) (n = 15), received an oral administration of 400 mg of ibuprofen-arginine, 90 min before surgery, 2 h after surgery and then every 8 h in the first 32 postoperative hours. The control group (group C) received in doubled blind a placebo at the same time. At 6 months, we looked after pain or dysesthesia. We confirmed the diagnosis of PMPS in presence of association of diagnosis criterias. Fourteen patients in each group have been included. Eighty-six percent of the patients (13 patients in group I and 11 patients in group C) presented at 6 months dysesthesia of the upper member ipsilateral to the mastectomy and/or the operated breast, appearing either immediately or after a laps of time. Nine patients (group I) and 6 patients (group C) had PMPS. Postoperative radiotherapy and lymphoedema were statistically associated with PMPS (p = 0.019 and p = 0.011). The perioperative preventive administration of a non-steroid anti-inflammatory drug reduces neither the incidence of pain in the first post-operative months, nor the appearance of PMPS at 6 months. These results suggest that others factors than the nervous lesion may play a role in the occurrence of PMPS, as radiotherapy, lymphoedema, but also psychosocials factors.

[Patient-controlled analgesia in cancer pain: practical aspects]. / L'analgésie auto-contrôlée dans les douleurs du cancer: aspects pratiques.

Allowing a suffering patient with cancer to control his pain is a challenge that numerous medical teams intend to take up. Although the best treatment is the etiologic one, in many situations the symptomatic and adjuvant therapies are both indispensable. Among them, the patient controlled analgesia (PCA) is a concept referring to the management of the pain, but also to the administration of some analgesic drugs. Even with genuine advantages the limits of the PCA do exist and need to be well known. PCA is not limited to palliative treatment; it can be used in many circonstances during each evolutionary step of the cancer, temporarily or for longer periods, at the hospital and at home as well. All patients disposing of such an equiment could determine their own best level of analgesia, at the good time, depending upon the temporal variability of the pain and its previsibility or not. The availability and the pedagogic concern of the members of the team, the link between the patient and his family, the involvement of both the regular general practioner and the "algologic" team are essential to maintain the best effects of this method.

[Quality control of care in a surgical department. Experience of the Fondation Berganié]. / Contrôle de la qualité des soins dans un service de chirurgie. Expérience de la Fondation Bergonié.

Activity in a surgical department can be evaluated quantitatively, but is should also be assessed qualitatively. One way to control the quality of care is to determine as accurately as possible the incidence of pre- peri- and post-operative complications and to analyse these date in a critical comparative study. This was accomplished in the surgical department of the Fondation Bergonié, Bordeaux during three test periods over the last five years--March 1987 (127 patients), June-July 1989 (276 patients), and June 1991 (147 patients). Results of this analysis cannot validly be compared with those of other departments with different patient recruitment and activity functions. However, this study within a department with regular, homogeneous activity did demonstrate, over a period of several years, a clear reduction in operative mortality, essentially by improved control of infectious complications by the extensive use of prophylactic antibiotic therapy for all surgery with a septic risk or for debilitated patients. Results also demonstrated the low cost effectiveness of routine pre-operative exploratory examinations.

[Symptomatic treatment of pain in cervico-facial cancers]. / Traitement symptomatique des douleurs des cancers cervico-faciaux.

Pain is frequent in patients presenting cervico-facial cancers. It can be acute or persistent, or present at the morbid entity known as chronic pain. The specific anatomical site and the often poor environment explain that the physical disability related to pain is increased by multiple psychosocial problems. Multidisciplinary care management by several actors is required and can be facilitated by a simple decision-making model. The schema presented can be used to prompt discussion and criticism. It needs constant improvement and extensions in order to reach a consensual attitude towards this king of suffering but also towards other situations of pain care management frequently encountered in cancer patients as well as those with other pathologies.

Decrease in zinc serum concentrations after surgical intervention. A study of 87 cases.

The post-surgery zinc depletion reported by Hallböök in 1977 and subsequently confirmed by many authors is now well known. Our study concerns a homogeneous group of 87 female patients undergoing the same surgical procedure: simple or enlarged hysterectomy. Results confirm a mean 35% drop in serum zinc after surgery compared to initial values. The drop is mainly during the operation. A parallel zinc and albumin depletion was noted in 36 patients between the beginning and end of intervention. More systematic zinc supplementation could be proposed before surgery in patients presenting chronic zinc depletion.

[Home parenteral nutrition in oncology, a information project]. / Nutrición parenteral domiciliaria en oncología, proyecto de informatización.

The increase in the indications for total parenteral nutrition (TPN) of long or medium term duration led to an investigation on a discontinued method during the night. The patient was thus free during the daytime. Cyclic parenteral nutrition (CPN) at home is a comfortable solution. Parenteral nutrition at home (PNH) enables the quality of life to be improved and also reduces the cost of the therapy, which may permit us to establish a structure for oncological patients to take advantage of PNH. In the specific case of oncology, we shall examine in the first place, the conditions, indications and counter indications, complications, advantages and structure operation. To improve on this method, we have introduced a data processing system that provides the doctor with more autonomy and assists in caring for the patient and in the therapeutical decision.

Detection of CD1 positive cells in the peripheral blood of patients suffering from cancer-associated malnutrition.

The immunological phenotyping of peripheral blood mononuclear cells (PBMC) was assayed in a series of 22 patients suffering from severe cancer-associated malnutrition. A marked decrease of the T-lymphocyte subsets (CD3+, CD4+, CD8+) and of the CD20+ B lymphocytes occurred; there was however an increased percentage of monocytes but their absolute number was normal. Interestingly, 5% of the PBMC expressed "activated T-cell antigens". The specificity of two different monoclonal antibodies (MoAbs) towards CD1 epitopes (OKT6 and D47) was assessed by indirect immunofluorescence (IIF): about 5% of CD1+ thymocytes were detected with no antigen (Ag) cross reactivity with the small subset of activated T cells. It is hypothesized that some relationship may exist between such cells and malnutrition and/or cancer.

[Approach to therapeutic risk by study of operative mortality. From 102 postoperative deaths between 1975 and 1984 at the Fondation Bergonié]. / Approche du risque thérapeutique par l'étude de la mortalité opératoire. A partir de 102 décès post-opératoires survenus en 10 ans (1975-1984) à la Fondation Bergonié.

A retrospective analysis of operative mortality in the cancer surgery department of the Fondation Bergonié between 1975 and 1984 allowed priority objectives to be defined requiring maximum efforts of the treating team. During this decade, 18,582 patients underwent surgery; 15,794 "first hand" operations were for cases not previously treated. Amongst the latter, 102 died within 90 days of surgery, 45 due to multifocal or apparently isolated pulmonary infection and 57 without any known infectious context. Separating patients into two groups: periods 1975-1979 and 1980-1984, demonstrated a notable decrease in postoperative mortality from 68 to 34. This improvement was due mainly to a reduction in deaths from infection (from 37 to 8 patients in the period 1980-1984). This marked improvement was probably the result of various combined causes: Mastery of parenteral nutrition enabling patients to be operated upon in better condition, or to tolerate possible complications better; Use of routine antibiotic therapy before surgery to digestive tube or ORL regions. These encouraging result suggest the need for enlargement of indications for routine prophylactic antibiotic therapy.

[Changes in the serum protein profile during radiotherapy of the upper respiratory and digestive tracts]. / Evolution du profil protéique sérique au cours de la radiothérapie des voies aéro-digestives supérieures.

Patients with a cancer of the upper airways or upper gastro-intestinal tract present a state of malnutrition as a result of the disease itself and, more importantly, as a result of its localisation. Loco-regional radiotherapy often leads to an aggravation of this state. The protein profile, consisting of nine serum proteins, was determined each week in 54 patients with cancer of the upper respirato-gastro-intestinal tract receiving radiotherapy. During the course of radiotherapy, the already altered nutritional state of these patients deteriorated further, as shown by a regular and significant downturn in the weight curve. The weekly monitoring of the protein profile showed a gradual and significant decrease in the levels of nutritional proteins (prealbumin, retinol binding protein, transferrin) and immunoglobulins (IgM, IgA) and a small variation in the levels of inflammatory proteins (haptoglobin, orosomucoid, C3 complement fraction, alpha 1-antitrypsin). The protein profile, established on the basis of carefully selected proteins, can provide useful information in the monitoring of a patient's nutritional state.

[General anesthesia in major cancer surgery of the upper respiratory and digestive tracts. Significance of a fentanyl-thiamine combination]. / L'anesthésie générale dans la chirurgie cancérologique majeure des voies aéro-digestives supérieures. Intérêt de l'association fentanyl- thiamine

Synaptanalgesia uses a polysynaptic inhibitor: thiamine and a powerful analgesic drug with or without nitrous oxide. This type of vigil or sub-vigil anesthesia used in major cancer surgery of the upper digestive tract and the airway, permits one to obtain: -efficacious protection of the autonomic nervous system, in spite of manipulations of highly reflexogenic areas, -a marked reduction in bleeding. The technique used is derived from that of other authors: DE CASTRO, MUNDELEER, VALENI, MAZZONI, GASPARETTO, adapting it to this type of surgery and attempting to simplify it.