2016 WSES guidelines on acute calculous cholecystitis.

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program.

S6 kinases (S6Ks) are mechanistic target of rapamycin substrates that participate in cell growth control. S6Ks phosphorylate ribosomal protein S6 (rpS6) and additional proteins involved in the translational machinery, although the functional roles of these modifications remain elusive. Here we analyze the S6K-dependent transcriptional and translational regulation of gene expression by comparing whole-genome microarray of total and polysomal mouse liver RNA after feeding. We show that tissue lacking S6Ks 1 and 2 (S6K1 and S6K2), displays a defect in the ribosome biogenesis (RiBi) transcriptional program after feeding. Over 75% of RiBi factors are controlled by S6K, including Nop56, Nop14, Gar1, Rrp9, Rrp15, Rrp12 and Pwp2 nucleolar proteins. Importantly, the reduced activity of RiBi transcriptional promoters in S6K1;S6K2(-/-) cells is also observed in rpS6 knock-in mutants that cannot be phosphorylated. As ribosomal protein synthesis is not affected by these mutations, our data reveal a distinct and specific aspect of RiBi under the control of rpS6 kinase activity, that is, the RiBi transcriptional program.

Pleomorphic adenoma of the nasal septum.

INTRODUCTION: Pleomorphic adenoma is the most common benign tumour of the salivary glands. The major salivary glands are most commonly involved, or more rarely accessory salivary glands, especially the oral cavity. Other locations, such as the nasal cavity, paranasal sinuses or upper aerodigestive tract, are exceptional. CASE REPORT: A 26-year-old female presented with right-sided nasal obstruction. Radiology found a lesion involving the anterior third of the nasal septum. The patient underwent complete surgical resection of the tumour via an endonasal approach. Histological examination found a mixed cellular component (epithelial and myoepithelial) and mesenchymatous tissue with chondromyxoid stroma, enabling diagnosis of a typical pleomorphic adenoma. DISCUSSION/CONCLUSION: Pleomorphic adenoma is exceptional in the nasal cavity, with only a few cases reported in the literature. Although benign, the risk of local recurrence, malignant transformation and metastasis requires close long-term follow-up.

The impact of individual human immunodeficiency virus type 1 protease mutations on drug susceptibility is highly influenced by complex interactions with the background protease sequence.

The requirement for multiple mutations for protease inhibitor (PI) resistance necessitates a better understanding of the molecular basis of resistance development. The novel bioinformatics resistance determination approach presented here elaborates on genetic profiles observed in clinical human immunodeficiency virus type 1 (HIV-1) isolates. Synthetic protease sequences were cloned in a wild-type HIV-1 background to generate a large number of close variants, covering 69 mutation clusters between multi-PI-resistant viruses and their corresponding genetically closely related, but PI-susceptible, counterparts. The vast number of mutants generated facilitates a profound and broad analysis of the influence of the background on the effect of individual PI resistance-associated mutations (PI-RAMs) on PI susceptibility. Within a set of viruses, all PI-RAMs that differed between susceptible and resistant viruses were varied while maintaining the background sequence from the resistant virus. The PI darunavir was used to evaluate PI susceptibility. Single sets allowed delineation of the impact of individual mutations on PI susceptibility, as well as the influence of PI-RAMs on one another. Comparing across sets, it could be inferred how the background influenced the interaction between two mutations, in some cases even changing antagonistic relationships into synergistic ones or vice versa. The approach elaborates on patient data and demonstrates how the specific mutational background greatly influences the impact of individual mutations on PI susceptibility in clinical patterns.

[Laryngeal Preservation with Induction Chemotherapy. Experience of two GETTEC Centers, Between 1985 and 1995]. / Préservation laryngée par chimiothérapie d'induction.

This is a retrospective study of laryngeal preservation in endolaryngeal cancer with induction chemotherapy and radiotherapy for good responders. Between 1985 and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and in Limoges (17 patients). The overall survival for the whole population was 76% and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation. In this retrospective series of patients, the single prognostic factor affecting survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85% and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%, p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55 pts) ). The percentages of patients with a fixed arytenoid could explain the conflicting results of the two randomized studies of laryngeal preservation in laryngeal cancer.

Subtotal laryngectomy with cricohyoidopexy as first treatment procedure for supraglottic carcinoma: Institut Gustave-Roussy experience (146 cases, 1974-1997).

PATIENTS AND METHODS: Between 1974 and 1997, 297 patients underwent a subtotal laryngectomy at the Institut Gustave-Roussy; 146 of these patients underwent cricohyoidopexy (CHP) for a supraglottic primary as their first treatment. The majority of patients were men (137) aged from 33 to 78 years (median 54 years). The tumour stage at presentation was T1 in 2, T2 in 87, T3 in 53 (preepiglottic space involvement), and T4 (minimal thyroid cartilage invasion) in 4 patients. One hundred and twenty-five patients were N0 (86%) and 21 patients were Np (palpable); 98% had homolateral and 55% had bilateral neck dissections. RESULTS: One patient died postoperatively of a myocardial infarction and 68% patients had an uneventful course. Aspiration was the commonest complication (23 patients, 19%). The median time to removal of the tracheotomy cannula was 10 days and for the nasogastric tube 21 days during the past 10 years. Completion of subtotal laryngectomy into total laryngectomy was done in 21 cases (15%): eight times because of oncological events [five local failures, two second primary (hypopharynx), one positive margin] and 13 times because of aspiration (9%). There were six local failures (4%) and eight nodal failures (5%). The rates of distant metastases and second primaries were 6% and 16% respectively. Half of the local and nodal failures were subsequently sterilized. Findings at death were two local recurrences, four nodal recurrences, eight distant metastases, and 11 second primaries. The 3- and 5-year overall survival rates were 92% and 88% respectively, with an overall laryngeal preservation rate of 86%. CONCLUSION: When supraglottic laryngectomy is not feasible for supraglottic cancer, subtotal laryngectomy with CHP is a safe and effective oncological procedure, with preservation of satisfactory laryngeal function.

Spontaneous coronary artery dissection presenting as acute myocardial infarction.

Spontaneous coronary artery dissection is a rare entity being increasingly diagnosed as a cause of acute myocardial infarction, especially in cases of low cardiac risk female patients. This is one such case report of a black female patient, who suffered an acute anterior wall myocardial infarction due to an idiopathic spontaneous coronary artery dissection of the left anterior descending artery. She was treated with a thrombolytic agent in the acute phase, uneventfully. An urgent coronary angiogram demonstrated an intimal tear with a dissection of the left anterior descending artery. She survived the acute event and her subsequent hospital course was uncomplicated. Hence she was treated medically for her ischemic event and left ventricular systolic dysfunction with a favorable outcome. This case is yet another report of a survivor treated with a thrombolytic agent for the acute myocardial infarction due to spontaneous coronary artery dissection.

Aesthesioneuroblastoma.

Forty patients were treated or followed up for aesthesioneuroblastoma between 1980 and 1995 at Institut Gustave Roussy, France. There were three T1, seven T2, 15 T3 and 15 T4 lesions. The cervical metastatic rate at presentation was 18 per cent. Distant metastases were detected by bone marrow biopsy and bone scan in three patients at presentation. Treatment modalities included surgery alone in eight patients, radiotherapy alone in three patients, combined modality surgery plus radiotherapy in 11 patients, chemotherapy alone in two patients, chemotherapy plus radiotherapy in 10 patients, and multimodality therapy chemotherapy plus surgery plus radiotherapy in six patients. The five-year survival rate was 51 per cent. Multimodality treatment offered better survival (63 per cent at five years) and disease-free interval (54 months). Overall local, regional, and distant failure rates were 58 per cent, 15 per cent and 40 per cent respectively. Distant metastases commonly occurred in bone (82 per cent). Cervical metastasis was an unfavourable prognostic indicator (0 per cent survival at two years). In conclusion, aesthesioneuroblastoma is sensitive to chemotherapy and radiotherapy. Multimodality therapy should be used initially.

Surgical treatment of carcinoma of the proximal esophagus.

BACKGROUND: Proximal esophageal cancer is usually diagnosed at an advanced stage, and the treatment is often limited to palliation. Surgery offers the best relief of dysphagia but it remains controversial, because a cure is unlikely even at the price of laryngeal mutilation. PATIENTS AND METHODS: We treated 40 patients with transhiatal esophagectomy for cancer of the proximal esophagus. The esophageal substitute was a stomach tube in 37 patients and colon in 3 patients. The larynx was preserved in 27 patients whose tumors did not extend to cricopharyngeus. Adjuvant treatment consisted of postoperative radiotherapy for 22 patients, chemotherapy for 1 patient, and a multimodality regimen for 4 patients. RESULTS: The postoperative complication and hospital mortality rates with gastric tube transpositions were 22% and 8%, respectively, with a 3% fistula rate. The 1- and 3-year overall survival rate was 53% and 21%, respectively. The unfavorable prognostic factors were tumor wall penetration, lymph nodal involvement, and cricopharyngeal involvement. Local recurrence of cancer was the major cause of failure. CONCLUSIONS: These results indicate that transhiatal esophagectomy with gastric tube transposition offers good palliation of dysphagia with low morbidity and mortality for proximal esophageal cancer. The laryngeal preservation can be attempted for tumors located close to, but not involving, the cricopharyngeus in order to retain speech in patients with a limited life expectancy.

Chondrosarcoma of the larynx.

A case of a low grade chondrosarcoma of the cricoid cartilage which had been diagnosed initially as a chondroma is presented. The tumour recurred twice after limited surgical resections. Total laryngectomy was inevitable due to near total involvement of the cricoid cartilage and subsequent histological examination revealed a low grade chondrosarcoma. We have discussed in brief, the diagnosis and treatment of chondrosarcomas of the larynx and support the view of conservative surgical management for low grade tumours as they are slow growing and metastases are infrequent. A total laryngectomy may be reserved for salvage or primarily when more than half of the cricoid cartilage needs to be resected. Histological grading reveals the biological behaviour of the tumour and CT scans help in planning the surgery. A regular follow-up is necessary for early detection of recurrences and metastases.

Sarcomas of nasal cavity and paranasal sinuses: chondrosarcoma, osteosarcoma and fibrosarcoma.

Forty-two patients were treated for sarcoma of the nasal cavity and paranasal sinuses at the Institut Gustave Roussy, Paris, between 1960 and 1993. Twelve patients had chondrosarcoma (CS), 14 had osteosarcoma (OS) and 16 had fibrosarcoma (FS). Ten patients had grade I, six grade II and 26 grade III tumours. All but 10 patients had surgery for the primary tumour. A significantly increased risk of local failure was associated with the male sex (p < 0.01), grade III tumours (p < 0.02) and patients excluded from surgery (p < 0.04). The overall incidence of local and distant failure was 76 and 12 per cent respectively. Overall survival was 28 per cent at three years and 23 per cent at five years. Eight patients (20 per cent) were alive more than 10 years later. The factors significantly influencing survival were sex (p < 0.01), grade (p < 0.05) and local failure (p < 0.01).

Gastric tube transposition for cancer of the hypopharynx and cervical oesophagus.

A study of 20 cases of gastric tube transposition following total laryngopharyngoesophagectomy during an eight-year period is presented. The site of the tumour was: hypopharynx in 13 cases (12 pyriform sinus, 1 post-cricoid); and cervical oesophagus in seven cases. There were nine (45 per cent) Stage III lesions and 11 (55 per cent) Stage IV lesions (UICC, 1987). Post-operative morbidity rate was 15 per cent. Hospital mortality rate was 10 per cent (cause of death was myocardial infarction). Anastomotic fistula rate was five per cent. Excluding hospital mortality, the three year actuarial survival rate was 35 per cent for the whole series and 53 percent for patients with hypopharyngeal cancer. The actuarial survival rate for patients with oesophageal cancer at one and two years was 41 and zero per cent respectively. The transposition of a tubed stomach provided successful swallowing in two-thirds of the patients for a period of more than a year and these patients developed good neoesophageal speech.

Primary and salvage surgery for cancer of the tonsillar region: a retrospective study of 120 patients.

The present series compares results in our head and neck department from primary and salvage surgery for tumors of the tonsillar region from 1978 to 1985. Of 120 consecutively admitted patients, 70 underwent primary surgery followed by irradiation, and 50 underwent salvage surgery after the failure of primary radiotherapy. Follow-up has been continued for the past 6 years. Musculocutaneous flaps were employed in all patients requiring them after the introduction of this reconstructive technique in 1981. The actuarial survival rate after primary surgery was 58% at 3 years and 46% at 5 years. For salvage surgery the figures were 38% and 24%, respectively. This disappointing survival rate in salvage surgery resulted from a higher postoperative mortality (8% versus 1.4% in primary surgery) and from a higher local failure rate (36% versus 14%). The outcome was invariably unfavorable when tonsillar tumors extended into the base of the tongue.

Osteoradionecrosis of the mandible: study of 104 cases treated by hemimandibulectomy.

One hundred and four cases of osteoradionecrosis (ORN) of the mandible following irradiation of head and neck cancer are reported. Conservative management for ORN failed in all cases. Indications of hemimandibulectomy included intractable pain, severe trismus, pathological fracture, oro-cutaneous fistula and persistent exposure of bone. Surgical approach was intra-oral in 100 cases and extra-oral in four. Immediate soft tissue reconstructions were carried out in 20 per cent cases. Post-operative complications included minor sepsis (8.6 per cent), major sepsis (2.9 per cent), haemorrhage (2.9 per cent) and fistula (3.8 per cent). Major complications occurred only in patients treated exclusively by external irradiation at doses equal to or higher than 65 Gy. Relief from pain and trismus was obtained and normal swallowing was established following radical surgery.

Adenoid cystic carcinoma of the salivary glands: clinicopathological survey of 51 patients.

A clinicopathological study of 51 cases of adenoid cystic carcinoma in the head and neck region seen over a period of 20 years is presented. The correlation between various histological features and their impact on the results is attempted. Longterm results with respect to loco-regional recurrences, distant metastases and survival with various modalities of therapy are presented. Although this is a small series, radical surgery in keeping with the aim of avoiding undue mutilation, thus preserving the quality of life, followed by a full course of radiotherapy has been the mainstay of treatment and the results here presented justify this approach.