Long-term survival after head and neck cancer surgery with immediate free flap reconstruction.

BACKGROUND: Head and neck cancer is one of the most frequent cancers worldwide. A combination treatment including surgery is known to have a better survival rate than exclusive radiotherapy-chemotherapy. In extreme cases of non-metastatic patients who have voluminous tumor, or complex location, surgery with immediate reconstruction by free flap could be an option to improve long term survival. PURPOSE: To share experience of long-term survival of patients with head and neck cancer who underwent oncologic surgery with immediate free flap reconstruction, and to analyze influencing factors. METHODS: All consecutive patients treated with free flaps for reconstruction of extensive defects after resection of head and neck cancer in our center (Nancy, France) were retrieved from the hospital database. Data was recorded in a systematic way. Bivariate and multivariate Cox proportional hazards models were used for statistical analysis. RESULTS: Between 1997 and December 2007, 70 patients underwent surgical resection of head and neck tumor with free flap reconstruction. 11 patients were excluded because of missing data. Follow-up time was 7.4 years, IQR from 4.3 to 11.3. Overall survival was 53.8%, 95% CI [39.9%; 65.8%] at 5 years and 38.6% [24.8%; 52.3%] at 10 years. Age>60 years at the surgery HR 2,373 (1,143; 4,927) and TNM score 3-4 HR 2,524 (1,093; 5,828) were statistically associated to a lesser survival rate. CONCLUSION: The ability to successfully and safely perform free flaps increases treatment options for patients with advanced head and neck cancer in a selected population. it seems worthwhile to perform these microvascular reconstructions.

Partial pharyngolaryngectomy with infrahyoid flap: Our experience.

AIM: We evaluated a cohort of advanced hypopharyngeal squamous cell carcinoma, treated with conservative surgery, reconstruction with infrahyoid flap and radio-chemotherapy. METHODS: We used partial pharyngo-laryngectomy and radio-chemotherapy to treat fifty-seven patients with stage III-IV hypopharyngeal SCC from November 1994 to December 2011. Clinical examination and speech therapy evaluation were used for estimation of laryngeal function. RESULTS: All patients received a partial pharyngo-laryngectomy. All patients underwent neck dissection; 56 patients received bilateral neck dissection. Reconstruction was achieved by infra-hyoid flap. Five-year overall and disease-specific survival rates were 54.4% and 61.4%, respectively. Successful laryngeal function preservation with complete five-year remission was achieved in 44% of the patients. CONCLUSION: Selected even if advanced carcinomas of the hypopharynx maybe treated with partial pharyngo-laryngectomy with reconstruction with pedicled flap. Both oncological and functional results showed a good outcome.

Using one-step nucleic acid amplification (OSNA) for intraoperative detection of lymph node metastasis in breast cancer patients avoids second surgery and accelerates initiation of adjuvant therapy.

BACKGROUND: Sentinel lymph node (SLN) analysis is conventionally analyzed using immunohistochemistry and in the case of SLN involvement, justifies a second surgery for axillary lymph node (ALN) resection, thus delaying the initiation of adjuvant therapies. PATIENTS AND METHODS: Three hundred and eighty-one patients with early stage breast cancer (BC) were considered in this retrospective study. SLNs were detected using combined radioisotope and dye detection. SLN involvement was analyzed using routine intraoperative One-Step Nucleic Acid Amplification (OSNA) assay, in 100 patients and compared with the conventional histopathology carried out previously in 281 patients. RESULTS: Considering positive SLNs as '++' (CK19 mRNA copy number>5000), '+' (250 < CK19 mRNA copy number <5000) and positive by inhibition in the OSNA group and macro-, micrometastases and isolated tumor cells in the histopathology group, no difference in SLN involvement rate was found between the two groups with 29.0% and 29.9% of positive SLNs, respectively. Using OSNA intraoperatively, the mean time to process the SLN was 42 min allowing immediate ALN resection, reduced significantly (P < 0.01) the re-intervention rate (9% versus 39%) and significantly (P < 0.01) accelerated the initiation of adjuvant therapy (6.2 versus 8.4 weeks). CONCLUSIONS: Using OSNA for intraoperative SLN analysis avoids second surgery for ALN resection in most patients and accelerates initiation of adjuvant therapy.

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma.

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.

Gender differences in the association between physical activity and cognitive function in individuals with bipolar disorder.

INTRODUCTION: Bipolar disorder (BD) is accompanied by a high number of comorbidities and associated with an overall increased mortality. Especially obesity, systemic inflammatory processes and cognitive deficits are highly prevalent and increase with the course of illness. Physical activity (PA) is associated with beneficial effects on somatic comorbidities such as obesity or cardiovascular disease in individuals without psychiatric disorder. Furthermore, PA might increase neurocognitive performance and reduce systemic inflammation. OBJECTIVE: The aim of the study was to investigate the association between PA and neurocognitive function in euthymic individuals suffering from BD. METHODS AND PARTICIPANTS: 120 individuals with BD, euthymic at test time, completed the self-reported International Physical Activity Questionnaire (IPAQ) assessing PA of the past seven days and were accordingly assigned to a specific activity category (low, moderate or vigorous). Furthermore, clinical parameters were gathered and cognitive tests analysing verbal-dependent intelligence, attention, executive functioning as well as memory were administered. RESULTS: Female individuals in the vigorous PA group performed significantly higher in most of the cognitive domains compared to females with moderate or low PA. In males, we only found a significant difference in one test for attention between moderate/vigorous and the low activity group. CONCLUSION: Differences between PA groups in cognitive performance in female individuals with BD were obvious in almost all cognitive domains. As cognitive deficits are strongly associated with a worse course of disease and outcome, PA might offer a concomitant therapy targeting not only somatic comorbidities such as obesity and cardiovascular disease, but also neurocognition.

Addressing parenting concerns of bone marrow transplant patients: opening (and closing) Pandora's box.

Although a significant number of adults undergoing stem cell transplant (SCT) or bone marrow transplantation (BMT) care for dependent children, and these treatments pose significant challenges for families, research has virtually ignored the impact of parenting on patients' quality of life during BMT/SCT and children's responses to having a parent undergo these treatments. Physicians rarely inquire about parenting concerns related to the extended hospitalizations necessitated by these treatments, yet clinical experience suggests that addressing patient concerns about children's reactions to cancer and BMT/SCT can improve the experience of the patient and the patient's family, and help the medical team respond effectively to sources of patients' distress. Parents frequently want to know what reactions to expect from children, thus general developmental information is reviewed, and recommendations given for when professional help for children is warranted. A key way for parents to support their children is with open, honest communication; however, parents often find it extremely difficult to talk about cancer and BMT/SCT with their children. The medical team can assist patients' efforts to communicate with and support their children by asking about a patient's children, providing some targeted information, and discussing the potential impact of treatments on parenting capacity. Inquiring about and addressing parenting concerns may initially seem difficult, but can ultimately facilitate stronger doctor-patient alliances, and more compassionate care.

Telerobotic-assisted laparoscopic hysterectomy for benign and oncologic pathologies: initial clinical experience with 30 patients.

BACKGROUND: Telerobotic-assisted laparoscopic attempts to provide technological solutions to the inherent limitations of traditional laparoscopic surgery. The aim of this study is to report the first experience of two teams concerning telerobotic-assisted laparoscopic hysterectomy for benign and malignant pathologies. METHODS: This study included 14 patients at the University Hospital Saint Pierre of Brussels (Belgium) and 16 patients at the Cancer Center of Nancy (France) from September 1999 to July 2003. RESULTS: The indications for surgery were uterine malignant diseases in 12 cases (stade I) (41%), and benign pathologies of the uterus in 18 cases (59%). Five postoperative complications (17%) occurred, none related to the robotic system. CONCLUSION: Robotic surgery can be safely performed in gynecologic and gynecologic-oncologic surgery with no increase in complication rates. A significant advance is represented by the surgeon's ergonomic improvement.

Transcriptional regulation of the Tn5276-located Lactococcus lactis sucrose operon and characterization of the sacA gene encoding sucrose-6-phosphate hydrolase.

The Lactococcus lactis sucrose operon was located on the conjugative transposon Tn5276 and the nucleotide sequence of the sacA gene, encoding sucrose-6-phosphate hydrolase, and its surrounding regions was determined. Northern blot analysis showed that the sucrose operon contains two divergent transcriptional units of 3.2 and 3.6 kb, the expression of which is considerably higher in cells grown on sucrose than in cells grown on glucose. This was confirmed by primer extension studies which demonstrated that transcription is initiated at two sucrose-inducible promoters with a back-to-back organization. The 3.2-kb transcriptional unit includes the sacB gene which most probably encodes the sucrose-specific enzyme II of the phosphotransferase system, and may contain the gene encoding fructokinase. The 3.6-kb transcriptional unit includes genes sacA and sacR. The protein encoded by the sacR gene is likely to be involved in the regulation of the sac operon expression, since its deduced N terminus is homologous to helix-turn-helix DNA-binding domains found in several regulatory proteins.

Development of a radioimmunoassay for papain.

Various well-tried radioimmunoassay (RIA) techniques were compared for the quantitation of papain. The evaluation of individual assays was performed by logit-log analysis. The most compatible analytical steps were combined in order to obtain the optimal analytical conditions of the assay. The preferred RIA involves papain labelling with lactoperoxidase, a double antibody method as the separation step and a 24 h incubation period at 2 degrees C. It permits the detection of 16 ng of papain per tube. In contrast, a method using immobilized antibody was satisfactory for rapid quantitation of papain with quite acceptable accuracy.

Factors affecting local control and survival after treatment of carcinoma of the rectum by endocavitary radiation: a retrospective study of 97 cases.

PURPOSE: Endocavitary radiation therapy constitutes an alternative to surgical therapy for some early rectal carcinomas. We studied the prognostic factors for locoregional or metastatic relapse after endocavitary radiation, and their impact for therapeutic strategy. METHODS AND MATERIALS: Our study reports the outcome of 97 patients with adenocarcinomas of the rectum treated from 1978 to 1998 by endocavitary irradiation (100 Gy), exclusive or combined with an interstitial brachytherapy boost of 20 Gy. The indications consisted mostly of polypoid, mobile tumors, less than 4 cm in diameter, and well differentiated. But the indications were extended to elderly patients, who presented with a high surgical risk or who refused mutilating surgery. RESULTS: The mean follow-up was 82 months. One patient presented with an isolated distant metastatic relapse, and 27 patients presented with locoregional recurrence, surgically salvaged in 16 cases. Disease-free survival was 71% at 5 years and 68% at 10 years. Multifactorial analysis suggests that clinical stage T1A, well-differentiated tumors, and early and complete response are favorable prognostic factors for disease-free survival. Response to therapy is the most powerful prognostic factor for relapse. CONCLUSION: This retrospective study confirms the efficacy of endocavitary radiotherapy combined with brachytherapy as a safe conservative treatment in well-selected patients.

Differential induction of cytochrome P-450 by the enantiomers of trans-stilbene oxide.

Optically pure (+)- and (-)-trans-stilbene oxide (TSO) enantiomers were administered to immature male Sprague-Dawley rats. (+)-TSO was the more potent inducer of liver microsomal cytochrome P-450-dependent monooxygenases. The greater potency of (+)-TSO may be explained on the basis of stereoselective metabolism since a far greater concentration of TSO was found in liver microsomes of (+)-TSO-treated rats. Furthermore, of the enzymes known to metabolize TSO, cytosolic epoxide hydrolase turned over the (-)-TSO enantiomer at a faster rate, consistent with the greater persistence of the (+)-enantiomer. Although this report is of chiral effects in potency of enzyme induction, stereoselective metabolism (i.e. disposition) rather than inherent structural characteristics (recognition) may be responsible for these effects.

Characterization of subclones of the epithelial cell line from Chironomus tentans resistant to the insecticide RH 5992, a non-steroidal moulting hormone agonist.

Selection of hormone resistant subclones in the continuous presence of the insecticide and ecdysteroid mimick RH 5992 (tefubenozide) resulted preferentially in clones with defects in ecdysteroid receptor function. RH 5992 is already degraded to polar products in wild-type cells; no increase in metabolism of tefubenozide is observed in resistant clones. According to Western blots, ecdysteroid receptor (EcR) and its heterodimerization partner ultraspiracle (USP) are present in all resistant clones. The concentrations are comparable to wild-type cells, but in three clones the extent of phosphorylation of USP is diminished. With regard to hormone binding several types of hormone resistance are distinguished: (1) The same two high-affinity hormone recognition sites are present as in wild-type cells (K(D1)=0.31+/-0.28 nM, K(D2)=6.5+/-2.4 nM) but the number of binding sites is reduced. (2) The binding site with the lower affinity (K(D2)) is missing. (3) The binding site with the higher affinity (K(D1)) is missing. (4) No specific binding is observed. Ponasterone A binding can be rescued by addition of EcR but not by USP. (5) Ligand specificity is altered. RH 5992 can not compete [(3)H]-ponasterone A as efficient as in wild-type cells.

Ecdysteroid receptor and ultraspiracle from Chironomus tentans (Insecta) are phosphoproteins and are regulated differently by molting hormone.

Three different isotypes of the ecdysteroid receptor (cEcR) (66, 68 and 70 kDa) and several molecular variants of the dimerization partner "ultraspiracle" (cUSP) (58-77 kDa) can be separated electrophoretically in homogenates of the epithelial cell line from Chironomus tentans. After phosphatase treatment the bands with the lowest electrophoretic mobility disappear in both cases. Phosphorylation occurs exclusively at ser/thr in EcR and USP. Binding studies with 3H-ponasterone A using 0.4 M NaCl extracts revealed two classes of high-affinity binding (KD1 = 0.47 and KD2 = 7.2 nM) competable either with 20-OH-ecdysone or muristerone A. At least KD2 and Bmax2 are unchanged after dephosphorylation. In hormonally naive cells a considerable part of EcR and USP is already present in nuclei. The phosphorylation pattern of both transcription factors is the same in cytosol and nuclear fractions. Incubation with 20-OH-ecdysone (1 microM, up to 4 days) does not alter the extent and mode of phosphorylation of EcR, although EcR concentration increases. In contrast USP concentration remains constant but phosphorylation is enhanced.

Functional characterization of two Ultraspiracle forms (CtUSP-1 and CtUSP-2) from Chironomus tentans.

Two forms, CtUSP-1 and CtUSP-2, of the Chironomus tentans homolog of Ultraspiracle (new nomenclature: Chironomus NR2B4) were described and verified as components of the functional ecdysteroid receptor. The two forms differed from each other in the most N-terminal regions of the A/B domain and were tested for several properties. Both forms showed the ability to heterodimerize with CtEcR and interact with a variety of direct repeat and palindromic EcREs, and both conferred specific ligand binding when heterodimerized with EcR. CtUSP-2 showed a twofold higher ponasterone-binding potential than CtUSP-1. Both USP forms demonstrated the ability to activate ecdysteroid-inducible transcription in HeLa cells and the variations in the A/B domain of these forms were not associated with detectable differences in transcriptional activation. Thus, the two forms function similarly. Among species for which USP forms have been reported, Chironomus is the most closely related one evolutionarily to Drosophila. Despite this proximity, a variety of structural differences were noted in both the A/B and E domains of USP between the two species. The Chironomus USP forms lack many of the amino acid residues associated with the ligand-dependent AF2 transactivation function found in all other RXRs and USPs reported so far.

Absolute kilovoltage calibration of a diagnostic x-ray generator.

A method for absolute calibration of diagnostic x-ray generators is presented and discussed. The method employs a Ge(Li) detector and relies on the direct observation of the onset of fluorescence radiation from scattering foils placed in the primary beam.

A time-course investigation of vitamin A levels and drug metabolizing enzyme activities in rats following a single treatment with prototypic polychlorinated biphenyls and DDT.

Xenobiotics previously characterized as selective inducers of drug-metabolizing enzymes were chosen to probe possible relationships between enzyme induction and vitamin A metabolism. Liver, kidney and serum retinol and retinyl palmitate levels were investigated in male Sprague--Dawley rats receiving a single i.p. injection of the polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumol/kg) or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) (150 mumol/kg). While 2,2',5,5'-tetrachlorobiphenyl, a weak or non-inducer, and 2,2',4,4',5,5'-hexaclorobiphenyl and DDT, phenobarbital-type inducers of cytochrome P-450, led to no reduction in total vitamin A content of liver or kidney during the 7 day time-course, administration of 3,3',4,4'-tetrachlorobiphenyl, a toxic PCB and a potent 3-methylcholanthrene-type inducer of cytochrome P-450, resulted in progressively lowered liver vitamin A levels (to 40% of control values by day 7). During this time, kidney total vitamin A content increased 3-fold. The increase in kidney vitamin A (due primarily to increased retinol content) was only equal to 1/40 of total vitamin A which had disappeared from the liver. Although 3,3',4,4'-tetrachlorobiphenyl specifically induced certain drug-metabolizing enzyme activities, e.g. aryl hydrocarbon hydroxylase and UDP-glucuronosyltransferase (toward 4-nitrophenol), no highly significant correlations were found among the vitamin A levels and drug-metabolizing enzyme activities in the liver (aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aldrin epoxidase, microsomal epoxide hydrolase, UDP-glucuronosyltransferase toward 4-nitrophenol, glutathione transferase toward 1-chloro-2,4-dinitrobenzene and cytochrome P-450 content) as determined by multiple linear regression analysis.

Pediatric dermatology: developmental and psychological issues.

Adolescence is characterized by a sensitivity to issues of attractiveness, emerging sexuality, and the challenge of parental rules and values. The latter tends to carry over into the relationship with other authority figures like the dermatologist. Noncompliance is a significant problem in treating this age group. It can be decreased by establishing an alliance with the patient concerning the goals of therapy. Although the parent may have brought in the teenager, the success of treatment depends on the patient himself or herself. The adolescent is most likely to follow through if the dermatologist presents the pros and cons of the treatment and explicitly leaves the choice of implementation to the adolescent. Parents who confidently offer to make sure the adolescent follows the treatment plan may only increase noncompliance by placing the treatment in the middle of existing parent-child struggles. For a variety of reasons, adolescents are hesitant to ask questions of the dermatologist, but this is especially true in sexually transmitted conditions. Teenagers may turn to each other and receive inaccurate information unless the physician actively invites their questions. In sexually transmitted illnesses this potentiates public health hazards, and in all dermatologic conditions it adversely affects compliance.

Screening for psychosocial dysfunction in pediatric dermatology practice.

The Pediatric Symptom Checklist, a brief psychosocial screening questionnaire, was used in a multi-center study of pediatric dermatology clinics (n = 377). Overall rates of positive screening indicated that approximately 13% of patients screened positive, a rate similar to findings in primary care pediatric settings. Examining the sample in greater detail demonstrated that children whose dermatologic disorder is perceived to have a greater impact on their appearance are at higher risk for psychosocial dysfunction.

The irreversibility of thiamin transport in Saccharomyces cerevisiae.

Neither exit nor counterflow efflux of thiamin, taken up previously by an active transport, were found in Saccharomyces cerevisiae, in either the wild type or a mutant with a lower rate of thiamin phosphorylation. Complete inhibition of thiamin phosphorylation by oxythiamin did not lead to any release of thiamin taken up by the cell.

[Results of a controlled trial comparing 3 suture threads at slow resorption for the closure of supra-umbilical midline laparotomies]. / Résultats d'un essai contrôlé comoparant 3 fils de suture à résorption lente pour la fermeture des laparotomies médianes sus-ombilicales.

A randomized prospective trial was carried out between September 1987 and February 1989 to compare 3 different absorbable sutures (polyglactine 910, polydioxanone I, polydioxanone II) for closure of the abdominal wall after upper midline laparotomy for elective operations. The technique used to close the fascia was always a continuous suture. The criteria used to assess the results were the development of wound infection and wound dehiscence in the early postoperative period, and the development of suture sinuses and incisional hernia 1 year after operation. The early postoperative results in 235 patients revealed no wound infection and no -wound dehiscence. Suture sinuses developed in 4 patients (2%) 2 months after operation, but resolved spontaneously. We reviewed 203 patients after one year. The total number of incisional hernias detected 1 year postoperatively was 22 cases (11%), (polyglactine 910, 14.2%; polydioxanone I, 11.2%; polydioxanone II, 8.4%). The difference between the 3 groups was not statistically significant. The results of the trial indicate that absorbable sutures have a very low incidence of suture sinuses, and that polydioxanone II seems to be a good choice for closing laparotomies.