Dissecting the brain's fear systems responding to snake threats.

We examined the behavioural responses and Fos expression pattern of rats that were exposed to snake threats from shed snakeskin and a live snake. We differentiated the behavioural responses and the pattern of Fos expression in response to the odour cues and mild threat from a live snake. Animals exposed to the snake odour alone or to the confined snake showed a great deal of risk assessment. Conversely, the intensification of odour during exposure to the live snake decreased the threat ambiguity, and the animals froze for a significantly longer period. Our Fos analysis showed that a pathway formed by the posteroventral part of the medial amygdalar nucleus to the central part of the ventromedial hypothalamic nucleus appeared to be solely responsive to odour cues. In addition, we showed increased Fos expression in a parallel circuit comprising the lateral amygdalar nucleus, ventral subiculum, lateral septum, and juxtadorsomedial region of the lateral hypothalamic area that is responsive to both the odour and mild threat from a live snake. This path is likely to process the environmental boundaries of the threat to be avoided. Both paths merge into the dorsal premammillary nucleus and periaqueductal grey sites, which all increase Fos expression in response to the snake threats and are likely to organize the defensive responses. Moreover, we found that the snake threat mobilized the Edinger-Westphal and supraoculomotor nuclei, which are involved in stress adaptation and attentional mechanisms.

Defensive behaviors and brain regional activation changes in rats confronting a snake.

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

Function evaluation of laryngeal reconstruction using infrahyoid muscle after partial laryngectomy in 37patients.

Treatment of small laryngeal cancerous lesions (T1 and T2) is based on partial endoscopic or open surgery and radiotherapy. In addition to the oncological imperative, these techniques must optimally preserve the functions of breathing, swallowing and phonation. OBJECTIVE: To analyze the above functions in patients treated with supracricoid laryngectomy and reconstruction using infrahyoid muscle. MATERIALS AND METHODS: Breathing, swallowing and phonation were analyzed in 37patients treated in two institutes between 2005 and 2015. All patients undergoing the above type of reconstruction with a minimum 1year's follow-up were included. Respiratory study noted any tracheotomy and measured peak inspiratory flow. Preservation of cricoarytenoid units and nasogastric intubation time, and DHI-30 self-administered questionnaire results were collected to analyze swallowing function. Phonation was assessed on the VHI-30 self-administered questionnaire. RESULTS: The rate of primary surgery without tracheotomy was 64.9% (13patients), with rapid resumption of oral feeding (mean intubation time, 13days). Mean VHI score was 28.3 and mean DHI 30score 2.7. Mean peak inspiratory flow was 203.3mL/min. CONCLUSION: Supracricoid laryngectomy with reconstruction using subhyoid muscle is an alternative technique for the treatment of small laryngeal cancerous lesions, providing uncomplicated functional outcome.

Spondylodiscitis after transoral robotic surgery: Retrospective 7-case series from the GETTEC group.

BACKGROUND: Cervical spondylodiscitis is a rare but severe complication of pharyngeal surgery. MATERIAL AND METHODS: This multicenter retrospective study reported all patients in the database of the French head and neck tumor study group (GETTEC) affected by cervical spondylodiscitis after transoral robotic surgery (TORS) for malignant pharyngeal tumor from January 2010 to January 2017. OBJECTIVES: To describe cases of post-TORS cervical spondylodiscitis, identify alarm signs, and determine optimal management of these potentially lethal complications. RESULTS: Seven patients from 6 centers were included. Carcinomas were located in the posterior pharyngeal wall. Tumor stage was T1 or T2. All patients had risk factors for spondylodiscitis. Mean time to diagnosis was 12.6days. The interval between surgery and spondylodiscitis diagnosis ranged from 20days to 4.5months, for a mean 2.1months. The most common symptom was neck pain (87%). Infections were polymicrobial; micro-organisms were isolated in 5 cases and managed by intravenous antibiotics, associated to medullary decompression surgery in 3 cases. Follow-up found favorable progression in 4 cases, and 3 deaths (mortality, 43%). CONCLUSION: This French multicenter study found elevated mortality in post-TORS spondylodiscitis, even in case of limited resection. Surgeons must be aware of this complication and alerted by persistent neck pain, fever, asthenia, impaired or delayed posterior pharyngeal wall wound healing or elevation of inflammatory markers. MRI is the most effective diagnostic radiological examination.

Assessment of swallowing function after circumferential pharyngolaryngectomy. A multicenter study by the GETTEC group.

OBJECTIVE: Circumferential pharyngolaryngectomy is performed for advanced pharyngeal tumor or in a context of postradiation recurrence. Several free or pedicle flaps have been described for pharyngeal defect reconstruction, with choice at the surgeon's discretion. The aim of this study was to evaluate long-term swallowing function according to the type of flap used for reconstruction. MATERIAL AND METHOD: A multicenter retrospective study was conducted from January to September 2016 within the French GETTEC head and neck tumor study group. All patients in remission after circumferential pharyngolaryngectomy were included and filled out the Deglutition Handicap Index (DHI) questionnaire and underwent swallowing function fiberoptic endoscopy assessment. 46 patients (39 men, 7 women) were included. Reconstruction used a tubularized forearm free flap (FFF group) in 19 cases, pectoralis major myocutaneous flap (PMMF group) in 15 cases and free jejunum flap (FJF group) in 12 cases. RESULTS: Mean DHI was 24: 20 in the FFF group, 23 in the FJF group and 25 in the PMMF group, without significant differences. 27 patients had normal swallowing, 9 mixed diet, 8 liquid diet and 3 were fed by gastrostomy. On endoscopy, free flaps (FJF and FFF) were associated with significantly greater rates of normal swallowing of saliva and yogurt than in the PMMF group (P=0.04). CONCLUSION: Type of flap reconstruction after circumferential pharyngolaryngectomy had no significant impact on postoperative swallowing function assessed on the self-administered DHI questionnaire.

Guidelines update: Post-treatment follow-up of adult head and neck squamous cell carcinoma: Screening for metastasis and metachronous esophageal and bronchial locations.

OBJECTIVE: The present article is an update of the guideline of the French Society of Otorhinolaryngology and Head and Neck Surgery (SFORL) on the post-treatment follow-up of adult head and neck squamous cell carcinoma concerning screening for metastasis and metachronous esophageal and bronchial locations. METHODS: A multidisciplinary work-group was entrusted with a review of the literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the work-group members' own experience. These were then reviewed by an editorial group independent of the work-group. A coordination meeting then finalized the guidelines. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence.

Laryngeal preservation in ENT oncology. Retrospective series of 246 patients managed in the Caen University Hospital and François Baclesse Cancer Care Center between 1998 and 2008.

OBJECTIVES: A 10-year retrospective study investigated factors for survival and laryngeal preservation in advanced laryngeal, hypopharyngeal or epilaryngeal neoplasia. MATERIAL AND METHOD: Two hundred and forty-six patients with advanced cancer of the larynx (17.48%), hypopharynx (48.78%) or epilarynx (33.74%) undergoing primary organ-sparing treatment were included from 1998 to 2008. Treatment comprised chemotherapy followed by radiation therapy for 92.68% of patients, isolated radiation therapy for 1.6% and concomitant or sequential radiation-chemotherapy for 5.7%. General health status, history and tumor status were recorded. Factors influencing survival were analyzed by Kaplan-Meier estimator, log-rank test and Cox models. RESULTS: Median overall survival of the population was 2.3 years and median laryngeal preservation 0.99 years in male patients and 2 years in female patients. Survival correlated significantly with body mass index (BMI; P=0.0004), WHO performance status (P=0.0064), alcohol consumption (P=0.0004) and cessation (P<0.0001) and also T stage (P=0.0038), initial laryngeal mobility (P=0.0002) and post-chemotherapy assessment (P<0.0001). Survival with functional larynx correlated with baseline BMI at first consultation (P=0.016), baseline WHO grade (P=0.0005), laryngeal mobility (P<0.0001), T staging (P=0.0009), and T and/or N chemotherapy response to a classical organ preservation protocol (P<0.0001). CONCLUSION: Over and above established criteria, the present study highlighted the importance of general health and nutritional status during treatment.

Management of somatic pain induced by treatment of head and neck cancer: Postoperative pain. Guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL).

OBJECTIVE: To present the guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL) concerning the management of somatic pain induced by the treatment of head and neck cancer, and in particular the management of early and late post-surgical pain. METHODS: A multidisciplinary work group conducted a review of the scientific literature on the study topic. An editorial group subsequently read the resulting guidelines before validation. RESULTS: It is recommended to prevent onset of pain caused by malpositioning on the operating table, as well as pain related to postoperative care. During surgery, it is recommended to spare nerve and muscle structures as far as possible to limit painful sequelae. Management of early postoperative pain upon tumor resection and flap harvesting sites requires patient-controlled analgesia by morphine pump. Physical therapy is recommended after flap harvesting to minimize painful sequelae. CONCLUSION: Preventive and curative measures should be undertaken for appropriate management of post-surgical pain in the treatment of head and neck cancers.

Management of somatic pain induced by head-and-neck cancer treatment: definition and assessment. Guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (SFORL).

OBJECTIVES: The authors present the guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (Société Française d'Oto-rhino-Laryngologie et de Chirurgie de la Face et du Cou [SFORL]) for the management of somatic pain induced by head-and-neck cancer treatment, and in particular the instruments needed for the definition and initial assessment of the various types of pain. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: The priority is to eliminate tumoral recurrence when pain reappears or changes following head-and-neck cancer treatment. Neuropathic pain screening instruments and pain assessment scales should be used to assess pain intensity and treatment efficacy. Functional rehabilitation sessions should be prescribed to reduce musculoskeletal pain and prevent ankylosis and postural disorder. Psychotherapy and mind-body therapy, when available, should be provided in case of chronic pain. In case of recalcitrant complex pain, referral should be made to a multidisciplinary pain structure. CONCLUSION: The management of somatic pain induced by head-and-neck cancer treatment above all requires identifying and assessing the intensity of the various types of pain involved, their functional impact and their emotional component.

Management of somatic pain induced by head and neck cancer treatment: pain following radiation therapy and chemotherapy. Guidelines of the French Otorhinolaryngology Head and Neck Surgery Society (SFORL).

OBJECTIVES: The authors present the section of the guidelines of the French Otorhinolaryngology Head and Neck Surgery Society (SFORL) for the management of somatic pain induced by head and neck cancer treatment concerning management of pain following radiation therapy and chemotherapy. METHODS: A multidisciplinary work group was entrusted with a literature review. Guidelines were drawn up based on the articles retrieved and the group members' experience. They were read over by an editorial group independent of the work group. A coordination meeting drew up the final version. Guidelines were graded A, B or C or as expert opinion in decreasing order of level of evidence. RESULTS: Particular care should be given to detection and early adapted treatment of pain induced by radiation therapy and/or chemotherapy, to improve quality of life in head and neck cancer patients.

Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results.

INTRODUCTION: Osteoradionecrosis (ORN) is a severe, generally irreversible complication of radiotherapy due to failure of healing. The pentoxifylline-tocopherol combination decreases the superficial fibrosis induced by radiotherapy. Potentiation by Clodronate (PENTOCLO) appears to be effective in ORN of the mandible. The objectives of this study were to evaluate the efficacy and safety of PENTOCLO to treat osteoradionecrosis of the mandible. METHODS: Retrospective study of 27 patients with a mean age of 65±12 years, managed for ORN of the mandible secondary to irradiation for head and neck cancer, treated by the PENTOCLO protocol between January 2010 and March 2011. The primary endpoint was regression of exposed bone until complete healing. Assessment was both clinical (measurement of mucosal ulceration) and radiological (panoramic dental x-rays) before treatment, after antibiotic-corticosteroid combination therapy for one month (M1), and then after 3, 6, 12 months of PENTOCLO. RESULTS: An improvement of mucosal ulceration was observed in 16/21 patients after 3 months and in 12/17 patients after 6 months of PENTOCLO. Healing was obtained in 16 patients. Median healing time was 82 days (range: 32-266), and was shorter after surgery and radiotherapy (49 days) and longer after chemoradiotherapy (169 days). Radiological healing was achieved later than clinical healing with improvement in 9 out of 20 patients at 3 months. The safety and efficacy of treatment were evaluated by intraoral clinical examination, and assessment of feeding, weight and analgesic consumption. No patient discontinued treatment because of adverse effects. CONCLUSION: The PENTOCLO protocol achieved clinical and radiological regression of ORN with, in parallel, a reduction of the indications for major surgery. These preliminary results need to be confirmed by prospective studies comprising quality of life assessment.

Cortagine infused into the medial prefrontal cortex attenuates predator-induced defensive behaviors and Fos protein production in selective nuclei of the amygdala in male CD1 mice.

Corticotropin-releasing factor (CRF) plays an essential role in coordinating the autonomic, endocrine and behavioral responses to stressors. In this study, we investigated the role of CRF within the medial prefrontal cortex (mPFC) in modulating unconditioned defensive behaviors, by examining the effects of microinfusing cortagine a selective type-1 CRF receptor (CRF1) agonist, or acidic-astressin a preferential CRF1 antagonist, into the mPFC in male CD-1 mice exposed to a live predator (rat exposure test--RET). Cortagine microinfusions significantly reduced several indices of defense, including avoidance and freezing, suggesting a specific role for CRF1 within the infralimbic and prelimbic regions of the mPFC in modulating unconditioned behavioral responsivity to a predator. In contrast, microinfusions of acidic-astressin failed to alter defensive behaviors during predator exposure in the RET. Cortagine microinfusions also reduced Fos protein production in the medial, central and basomedial, but not basolateral subnuclei of the amygdala in mice exposed to the rat predatory threat stimulus. These results suggest that CRF1 activation within the mPFC attenuates predator-induced unconditioned anxiety-like defensive behaviors, likely via inhibition of specific amygdalar nuclei. Furthermore, the present findings suggest that the mPFC represents a unique neural region whereby activation of CRF1 produces behavioral effects that contrast with those elicited following systemic administration of CRF1 agonists.

Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

OBJECTIVE: Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. METHOD: Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. STUDY CENTRES: CLCC François-Baclesse and CHU de Caen. PATIENTS: Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). RESULTS: In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. CONCLUSION: In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%.

[Thyroid differenciated carcinoma in children. Study from Normandy]. / Cancers thyroïdiens différenciés de l'enfant. l'expérience normande.

OBJECTIVE: Definition of a strategy for the management of thyroid differenciated carcinoma in children. DESIGN AND SETTING: Retrospective cohort study from the Normandy area in France. METHOD: Analysis of the medical records of 13 children and adolescents (age > 15 years), presenting with thyroid differenciated carcinoma in three Normandy French hospitals from 1994 to 2006, to determine the clinical features and treatment of the disease. RESULTS: X of the patients were male and y were female, with a mean age at presentation of 11 years. Most frequently symptom was solitary nodes in the thyroid gland (69%). Most frequent histological type was papillary cancer (92%). Size of tumor was > 4 cm in 23% of cases. Children had undergone surgery with total thyroidectomy, radio-iodine treatment and suppressive hormonotherapy. We observed 46% post surgery complications. All patients were alive and none developed a recurrence. CONCLUSION: Thyroid differenciated carcinoma in children and adolescents were more agressif with most frequently metastasis and recurrence than thyroid differenciated carcinoma of adults. Pronostic is good with 90% of survival at 20 years. We propose a coherent plan of treatment: 1. Thyroidectomy with cervical central lymph node dissection (group VI) completed bilateral selected head neck dissection compartments (groups IIa, III, IV) if macroscopic lymph node metastases in lateral cervical compartment. 2. Postoperative radioiodine is done in all tumor > T1N0 and completed with hormonotherapy.

[Esophageal foreign body: dental plate]. / Corps étranger esophagien: prothèse dentaire.

OBJECTIVE: Describe clinical characteristics and management of dental esophageal foreign body. PATIENT AND METHODS: Observation of a denture wedged in the esophagus in a 55 year man and literature review of cases reported in the literature. RESULTS: Enclosing risk factors for esophageal foreign body of dental origin are the altered consciousness, old persons, and local factors. The diagnosis is suspected with chest radiography and confirm by endoscopy. The therapeutic management with extraction of the foreign body is endoscopic and / or surgery. Complications a e related to time taken and can be sometimes serious. CONCLUSION: The diagnosis of esophageal dental foreign body should be considered in any dysphagia in predisposing persons. The diagnosis may require endoscopy. Prevention go through information of actors in specialized institutes.

[Cranial fasciitis of childhood]. / Fasciite crâniale.

OBJECTIVE: To describe the clinical and pathological features of cranial fasciitis of childhood, and to review and compare this case with those of international literature. METHODS: We report a case of cranial fasciitis of childhood located on the face of a 13-month-old boy. A complete review was performed from the database "Pub Med", looking for the key words "head and neck inflammatory myofibroblastic tumour", "nodular fasciitis", "cranial fasciitis of childhood". RESULTS: Cranial fasciitis is benign rapidly growing fibroblastic tumour, belonging to the group of nodular fasciitis, and has a predilection for the head and neck region of young children. This tumour is highly cellular and often show striking erosion of bone often misdiagnosed as a sarcoma. Surgery with adequate resection margin is the best treatment. There is no tendency for local recurrence. CONCLUSION: Positive pathological diagnosis of cranial fasciitis is uncommon and may be difficult.

[Iatrogenic dissection of the right coronary artery and the ascending aorta during coronary intervention]. / Dissection iatrogène de la coronaire droite et de l'aorte ascendante au cours d'une procédure d'angioplastie.

Iatrogenic acute dissection of the ascending aorta following coronary angiography and percutaneous intervention is rare. The options for treatment are dictated by patient stability, nature of dissection of the coronary vessel, ability to restore the coronary circulation and extent of aortic dissection. Usually localized aortic dissections have been managed conservatively or treated by sealing the entry with a coronary stent. Extensive dissections may require a surgical intervention. We report the case of a 52-year-old man with iatrogenic dissection of the right coronary artery ostium and extension of the dissection to the ascending aorta during intraluminal angioplasty of an obstructive lesion in the first portion of the right coronary artery. The patient was managed conservatively without stenting (failure stenting of the right coronary artery) and without surgery. Aortic dissection was monitored by means of transesophageal echocardiography. Serial computed tomography scans demonstrated spontaneous resolution of the dissection. The evolution of the patient was satisfactory. Causes, frequency and treatment procedures of this iatrogeny are discussed.

Neural correlates of scent marking behavior in C57BL/6J mice: detection and recognition of a social stimulus.

Mice show urinary scent marking behavior as a form of social communication. Marking to a conspecific stimulus mouse or odor varies with stimulus familiarity, indicating discrimination of novel and familiar animals. This study investigated Fos immunoreactivity in inbred C57BL/6J (C57) males following scent marking behavior in response to detection of a social stimulus, or discrimination between a familiar and an unfamiliar conspecific. In Experiment 1 C57 mice were exposed for four daily trials to an empty chamber; on a test day they were exposed to the same chamber or to a male CD-1 mouse in that chamber. Increased scent marking to the CD-1 mouse was associated with increased Fos-immunoreactive cells in the basolateral amygdala, medial amygdala, and dorsal and ventral premammillary nuclei. In Experiment 2 C57 mice were habituated to a CD-1 male for 4 consecutive days and, on the 5th day, exposed to the same CD-1 male, or to a novel CD-1 male. Mice exposed to a novel CD-1 displayed a significant increase in scent marking compared to their last exposure to the familiar stimulus, indicating discrimination of the novelty of this social stimulus. Marking to the novel stimulus was associated with enhanced activation of several telencephalic, as well as hypothalamic and midbrain, structures in which activation had not been seen in the detection paradigm (Experiment 1). These included medial prefrontal and piriform cortices, and lateral septum; the paraventricular nuclei, ventromedial nuclei, and lateral area of the hypothalamus, and the ventrolateral column of the periaqueductal gray. These data suggest that a circumscribed group of structures largely concerned with olfaction is involved in detection of a conspecific olfactory stimulus, whereas discrimination of a novel vs. a familiar conspecific stimulus engages a wider range of forebrain structures encompassing higher-order processes and potentially providing an interface between cognitions and emotions.

Association of surgery with improved survival in stage IV breast cancer patients.

OBJECTIVE: This study aims to examine the role of surgery in patients with stage IV breast cancer. BACKGROUND: Historically, women who present with metastatic breast cancer are not offered surgical treatment. However, recent reports indicate that surgery may improve outcome. Using a large database of women whom presented with stage IV breast cancer, we compared outcome of patients who had resection of their primary cancer to those who did not. METHODS: Of 16,401 patients, 807 had stage IV disease at presentation, and 395 survived >90 days and were included in this analysis. Clinical and tumor characteristics, surgical treatment, and survival were compared for the surgically versus nonsurgically treated patients. RESULTS: Two hundred and forty-two patients (61.3%) had definitive surgery for their primary tumor and 153 (38.7%) did not. Patients who underwent surgery were significantly older, were more likely to be white, more often had hormone receptor positive disease, had small primary tumors, and had fewer metastatic sites and less visceral involvement. The median survival of surgically treated patients was 27.1 months versus 16.8 months for patients without surgical resection (P < 0.0001). In multivariate analysis, which included surgical treatment, age, race, estrogen and progesterone receptor status, number of metastatic sites, and presence of visceral metastases, surgery remained an independent factor associated with improved survival (P = 0.006). CONCLUSION: Patients with stage IV breast cancer who had definitive surgical treatment of their primary tumors had more favorable disease characteristics. However, after adjustment for these characteristics, surgical treatment remained an independent factor associated with improved survival.

Characterization of primary breast carcinomas grown in three-dimensional cultures.

BACKGROUND: The process of progression and spread of cancer is not easily replicated in animal models and is difficult to examine in vitro. This is particularly true for human primary breast carcinoma cells, whose in vitro growth is shown to be limited to one or two passages in monolayer culture. Three-dimensional (3D) growth of breast cancer cells suggests that cell aggregates grown in this manner have many similarities to in vivo behavior. MATERIALS AND METHODS: Primary tumors obtained from five breast cancer patients were grown in 3D cultures using the rotating-wall vessel bioreactor. Tumor aggregates were assessed for DNA ploidy, cell cycle kinetics, and expression of tumor markers and cytokines. Comparisons between fresh tumor cells and 3D aggregates were performed. RESULTS: All five breast cancers were found to be aneuploid after 3D culture, with elevated S-phase fractions. Reverse transcription-polymerase chain reaction analyses revealed mRNA expression of HER2/neu, H-ras, K-ras, p53, transforming growth factor-alpha, transforming growth factor-beta, interleukin-1, and interleukin-6 in 3D-grown tumor cells; in most cases, expression appeared increased when compared with mRNA obtained from freshly isolated primary tumor cells. CONCLUSIONS: After prolonged 3D growth in the rotating wall bioreactor, complex tissue-like constructs of primary breast tumor cells exhibited significantly increased proliferative activity in conjunction with oncogene activation and developed into aggressive aneuploid populations.