Minimally Invasive Parathyroidectomy without Intraoperative PTH Performed after Positive Ultrasonography as the only Diagnostic Method in Patients with Primary Hyperparathyroidism.

BACKGROUND: A positive and concordant result of at least two diagnostic modalities is generally recommended prior to focused parathyroidectomy. The aim of this study was to analyze the results of surgery and the accurateness of preoperative ultrasonography (US) as single localization modality in patients who underwent parathyroidectomy without the adjunct of intraoperative Parathormone (PTH) measurement. METHODS: The cases with a preoperative US as the only localization technique, who underwent parathyroidectomy between 10/1999 and 12/2017, were selected from a prospectively maintained database. Therefore, a total number of 242 patients with a mean age of 58.6 ± 13.7 years were included in the present study. US was performed by referral endocrinologist or by the surgeon during office visits. RESULTS: The overall "cure rate" was 99.2% (240 out of 242 patients). In 228/242 patients (94.2%), a drop of perioperative PTH levels consistent with the definition of cure was observed on the day of surgery. In four of the remaining 14 patients, healing was confirmed by PTH level dropping into the normal range on the first postoperative day. Eight patients were cured after a reoperation was performed at our department. Postoperative complications included one case of permanent recurrent laryngeal nerve palsy (0.4%). CONCLUSIONS: If performed by an experienced endocrinologist and/or endocrine surgeon, a positive US could be the only preoperative localization study in patients with pHPT. Moreover, the add-value of intraoperative PTH is limited. Major advantages of US are a very high accuracy, the ease of performance (accessibility) and its cost-effectiveness compared with Sesta-MIBI scintigraphy.

Skeletal Muscle Attenuation (Sarcopenia) Predicts Reduced Overall Survival in Patients with Advanced Epithelial Ovarian Cancer Undergoing Primary Debulking Surgery.

BACKGROUND: Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS: Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]). The optimal cut-off point for MA (32 HU) was calculated using the Martingale residuals method, and previously reported cut-offs for SMI were used. Logistic regression was used to determine univariate and multivariate factors associated with OS. RESULTS: Sarcopenia defined as SMI < 38.5, < 39, and 41 cm2/m2 was detected in 29.4, 33.7, and 47.1% of patients, respectively; however, none of these SMI cut-off levels were associated with OS. MA < 32 HU was present in 21.1% (68/323) of the total cohort. Significant differences between patients with MA < 32 and ≥ 32 HU were detected for median age (67 vs. 57 years), Eastern Cooperative Oncology Group (ECOG) > 0 (13.2 vs. 3.1%), comorbidity (age-adjusted Charlson Comorbidity Index [ACCI] ≥ 4; 36.8 vs. 13.3%), median body mass index (BMI; 27 vs. 24 kg/m2), International Federation of Gynecology and Obstetrics (FIGO) stage, histology (high-grade serous 95.6 vs. 84.7%), and complete resection (38.2 vs. 68.2%). MA < 32 HU remained a significant prognostic factor for OS in multivariate Cox regression analysis (hazard ratio 1.79, p = 0.003). Median OS in patients with MA < 32 HU versus MA ≥ 32 HU was 28 versus 56 months (p < 0.001). Furthermore, MA < 32 HU was significantly associated with OS in the prognostically poor population of patients with residual tumor (p = 0.015). CONCLUSIONS: Low MA was significantly associated with poor survival, especially in patients with residual tumor after PDS. MA assessment could be used for risk stratification after PDS.

Prognostic Value of the Age-Adjusted Charlson Comorbidity Index (ACCI) on Short- and Long-Term Outcome in Patients with Advanced Primary Epithelial Ovarian Cancer.

BACKGROUND: We evaluated the prognostic impact of the age-adjusted Charlson Comorbidity Index (ACCI) on both postoperative morbidity and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) treated at a tertiary gynecologic cancer center. PATIENTS AND METHODS: Exploratory analysis of our prospectively documented tumor registry was performed. Data of all consecutive patients with stage IIIB-IV ovarian cancer who underwent primary cytoreductive surgery (PDS) from January 2000 to June 2016 were analyzed. Patients were divided into three groups, based on their ACCI: low (0-1), intermediate (2-3), and high (≥4), and postoperative surgical complications were graded according to the Clavien-Dindo classification (CDC). The Fisher's exact test, log-rank test, and Cox regression models were used to investigate the predictive value of the ACCI on postoperative complications and OS. RESULTS: Overall, 793 consecutive patients were identified; 328 (41.4%) patients were categorized as low ACCI, 342 (43.1%) as intermediate ACCI, and 123 (15.5%) as high ACCI. A high ACCI was significantly associated with severe postoperative complications (CDC 3-5; odds ratio 3.27, 95% confidence interval 1.97-5.43, p < 0.001). Median OS for patients with a low, intermediate, or high ACCI was 50, 40, and 23 months, respectively (p < 0.001), and the ACCI remained a significant prognostic factor for OS in multivariate analysis (p = 0.001). The same impact was observed in a sensitivity analysis including only those patients with complete tumor resection. CONCLUSION: The ACCI is associated with perioperative morbidity in patients undergoing PDS for EOC, and also has a prognostic impact on OS. The potential role of the ACCI as a selection criteria for different therapy strategies is currently under investigation in the ongoing, prospective, multicenter AGO-OVAR 19 trial.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

OBJECTIVE: To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. METHODS: We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. RESULTS: AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). CONCLUSION: In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections.

A randomized controlled bicenter trial of yoga for patients with colorectal cancer.

OBJECTIVE: The aim of this trial was to evaluate the effects of yoga on health-related quality of life in patients with colorectal cancer. METHODS: Patients with non-metastatic colorectal cancer were randomly assigned to a 10-week yoga intervention (90 min once weekly) or a waitlist control group. Primary outcome measure was disease-specific quality of life (Functional Assessment of Cancer Therapy - Colorectal [FACT-C]) at week 10. Secondary outcome measures included FACT-C subscales: spiritual well-being (FACT - Spirituality); fatigue (FACT - Fatigue); sleep disturbances (Pittsburgh Sleep Quality Inventory); depression and anxiety (Hospital Anxiety and Depression Scale); body awareness (Scale of Body Connection); and body-efficacy expectations (Body-Efficacy Expectations Scale). Outcomes were assessed at week 10 and week 22 after randomization. RESULTS: Fifty-four patients (mean age 68.3 ± 9.7 years) were randomized to yoga (n = 27; attrition rate 22.2%) and control group (n = 27; attrition rate 18.5%). Patients in the yoga group attended a mean of 5.3 ± 4.0 yoga classes. No significant group differences for the FACT-C total score were found. Group differences were found for emotional well-being at week 22 (∆ = 1.59; 95% CI = 0.27,2.90; p = 0.019), sleep disturbances at week 22 (∆ = -1.08; 95% CI = -2.13, -0.03; p = 0.043), anxiety at week 10 (∆ = -1.14; 95% CI = -2.20, -0.09; p = 0.043), and depression at week 10 (∆ = -1.34; 95% CI = -2.61, -0.8; p = 0.038). No serious adverse events occurred in the yoga group, while liver metastases were diagnosed in one patient in the control group. CONCLUSION: This randomized trial found no effects of yoga on health-related quality of life in patients with colorectal cancer. Given the high attrition rate and low intervention adherence, no definite conclusions can be drawn from this trial.

Feasibility of video-assisted bilateral neck exploration for patients with primary hyperparathyroidism and failed or discordant localization studies.

PURPOSE: Minimally invasive video-assisted parathyroidectomy (MIVAP) is generally adopted for patients affected by primary hyperparathyroidism (pHPT) with clear preoperative localization. Standard bilateral neck exploration (BNE) is considered the obligate surgery for patients with unlocalized glands. We reviewed our experience of minimally invasive video-assisted BNE in patients with pHPT and negative or discordant localization studies. METHODS: From a prospective series of 576 MIVAP for pHPT, 107 patients (19 males, 88 females; mean age 58 years) with failed localization studies underwent BNE using the video-assisted technique. Operative time, complications, conversions to standard cervical exploration, and cure rate were analyzed. RESULTS: MIVAP with BNE was successfully completed in 99 (93 %) patients with 8 conversions. Mean operative time was 57 ± 37 min (range 20-180 min). Permanent recurrent laryngeal nerve palsy occurred in one patient. Biochemical cure was achieved in 104 patients (97 %). Five patients required a reoperation in the immediate postoperative period, which achieved cure in four. Two patients remained with persistent disease; one developed recurrence disease 3 years after the first exploration. CONCLUSION: In experienced hands, video-assisted BNE for pHPT is feasible and safe and provides results equivalent to the conventional open technique.

Intraoperative neuromonitoring does not reduce the incidence of recurrent laryngeal nerve palsy in thyroid reoperations: results of a retrospective comparative analysis.

PURPOSE: Recurrent laryngeal nerve (RLN) palsy is the major concern of reoperative thyroid surgery, and the introduction of neuromonitoring could reduce the rate of this complication. The present study is a retrospective analysis of the experience with completion thyroidectomy with and without neuromonitoring in a referral center. METHODS: Between October 1999 and April 2011, 246 patients [37 men, 209 women; mean age, 55 ± 12.5 (range, 25-80) years] underwent 250 reoperations for recurrent goiter (n = 203), hyperthyroidism (n = 26), or recurrent thyroid cancer (n = 17). The mean interval between the initial and the reoperative procedure was 17.5 years. According to the availability of the neuromonitoring system and to the surgeon preference, 91 operations were performed with neuromonitoring (NM-group), whereas 159 were performed with direct nerve visualization (NV-group) alone. Patients' characteristics, perioperative data, and postoperative complications were collected in a prospectively maintained database. RESULTS: In the NM-group, 51 unilateral and 40 bilateral resections were performed. The NV-group included 122 unilateral and 37 bilateral procedures. The number of nerves at risk after previous surgery was 128 (NM-group) and 161 (NV-group), respectively. We registered eight RLN palsy in the NM-group (6.2 %) and four in the NV-group (2.5 %; p = 0.1). CONCLUSIONS: The routine use of intraoperative neuromonitoring seems not to reduce the incidence of RLN during redo thyroid surgery, at least in the setting of a tertiary referral center.

Minimally invasive cortical-sparing surgery for bilateral pheochromocytomas.

INTRODUCTION: Cortical-sparing adrenalectomy in bilateral pheochromocytomas offers a postoperative corticoid-free course and has to be balanced against the risk of local recurrence. In this study we report our experience with the minimally invasive cortical-sparing adrenalectomy in patients with bilateral pheochromocytomas. METHODS: From January 1996 to February 2011, 66 patients (45 men, 21 women; mean age 36 ± 16 years) were treated for bilateral pheochromocytomas. Fifty-seven patients (88%) were affected by genetic diseases. In 32 patients surgery was synchronously performed on both side, in 34 cases adrenalectomy followed previous surgery. All in all, 101 operations (47 right, 54 left) were conducted using the retroperitoneoscopic access (n = 97) or the laparoscopic route (n = 4). RESULTS: The mortality in our series was zero. Postoperative complications included one patient with a bleeding requiring reoperation and one patient developing a cerebral stroke on the fifth postoperative day. The mean operative time was 67 ± 26 min for unilateral adrenalectomy and 128 ± 68 min for bilateral surgery (range 25-300 min). A cortical-sparing resection was possible in 89 procedures resulting in a corticoid-free postoperative course in 60 patients (91%). A postoperative corticosteroid substitution therapy was necessary in six patients. During a median follow-up period of 48 months, one patient showed a persistent disease and needed reoperation, none developed a recurrent disease. CONCLUSION: Cortical-sparing surgery for bilateral pheochromocytomas has a low recurrence rate and avoids lifelong cortisone substitution therapy in the majority of cases.

Posterior retroperitoneoscopic adrenalectomy for clinical and subclinical Cushing's syndrome.

BACKGROUND: Because of co-morbidity, adrenalectomy for adrenal Cushing's syndrome may be associated with an increased complication rate and long operating times. In the present study we report our experience with the posterior retroperitoneoscopic adrenalectomy in a large group of patients with clinical or subclinical Cushing's syndrome. PATIENTS AND METHODS: Between July 1994 and June 2009, 170 patients (17 males, 153 females age 50 +/- 13 years; range: 12-78 years) affected by Cushing's syndrome underwent operation via posterior retroperitoneoscopic access. Patients were divided into two groups, those with manifest Cushing's syndrome (mCS) [99 patients: 6 male, 93 female; age 45 +/- 13 years] and those with subclinical Cushing's syndrome (sCS) [71 patients: 11 male, 60 female; age: 56 +/- 11 years]. The sCS classification was assumed in cases without typical clinical symptoms but with a pathological dexamethasone suppression test. Partial adrenalectomy was performed in 35 cases (24 in the mCS-group and 11 in the sCS-group). RESULTS: Mortality was zero; major complications did not occur. The incidence of postoperative minor complications was 5.3%. Mean operating time was 58 +/- 36 min (range: 20-230 min) and did not differ between mCS and sCS patients (58 versus 59 min; p = ns). Postoperative oral steroids supplementation (POSS) was administered in 136 patients (99 mCS, 37 sCS). If POSS was started, mean duration of therapy was 12.3 months (mCS) and 10.3 months (sCS) [p = 0.08], respectively. After a mean follow-up of 70.9 +/- 46.5 months the cure rate was 99.4%. CONCLUSIONS: The posterior retroperitoneoscopic approach is fast and safe even in patients with Cushing's syndrome. Partial adrenalectomy represents a new option in the treatment of cortisol-producing adenomas.

Synthesis, characterisation and insulin-mimetic activity of oxovanadium(IV) complexes with amidrazone derivatives.

The complexation of VO(2+) ion by ten acetamidrazone and 2-phenylacetamidrazone derivatives (L) was studied. Sixteen novel VO(2+) complexes were synthesised and characterised through the combined application of analytical and spectroscopic (EPR (electron paramagnetic resonance), FT-IR and diffuse reflectance electronic absorption) techniques. Eight are 1:2 species of composition [VOL(2)]SO(4) x xH(2)O and eight are 1:1 species with formula [VOL(SO(4))](n) x xH(2)O. The experimental data suggest a bidentate coordination mode for L with the donor set formed by the imine nitrogen and the carbonyl oxygen. EPR spectra indicate a square-pyramidal geometry for the 1:1 complexes and a penta-coordinated geometry intermediate between the square-pyramid and the trigonal-bipyramid for the 1:2 species. The hyperfine coupling constant along z axis, A(z), of the 1:2 complexes exhibits a marked reduction with respect to the predicted value (approximately 148x10(-4)cm(-1) vs. approximately 170x10(-4)cm(-1)). IR spectroscopic evidence supports the presence of sulphate as a counter-ion in the 1:2, and as a bridging bidentate ligand in the 1:1 complexes. Insulin-mimetic tests on modified fibroblasts, based on a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide) assay, performed on three of the bis-chelated and eight of the mono-chelated derivatives, indicate that they are biologically active. The similar hydro/lipophilicity and the lack of ligand substituents recognizable by cell membrane receptors prevent substantial differentiation in the insulin-mimetic action.

Chlorhexidine in cleft lip and palate patients with multibracket appliances. Results of a prospective study on the effectiveness of two different chlorhexidine preparations in cleft lip and palate patients with multibracket appliances.

AIM: The aim of this study is to reduce the caries risk in cleft lip and palate (CLP) patients with multibracket appliances via a compliance-independent method. PATIENTS, MATERIALS AND METHODS: Sixty-eight CLP patients with multibracket appliances were submitted to professional tooth cleaning at 4-week intervals. After randomization, patients in group A wore a splint filled with chlorhexidine (CHX) gel (Chlorhexamed) for 15 minutes (3 x 5 min) every 12 weeks. Patients in group B were treated with CHX varnish (EC40) every 12 weeks. Fluoride varnish (Fluoridin) was applied to all teeth 4 and 8 weeks after the respective CHX treatments. Regular salivary bacteria counts (CRT) were carried out to determine therapeutic effectiveness. Initial DMFS values were compared to the final ones. RESULTS: Initial findings of the salivary test and DMFS index confirmed the high caries risk. The DMFS value increased dramatically in both groups despite this systematic prophylaxis program. The bactericidal effect of both CHX preparations turned out to be markedly weaker than that described in the literature. CONCLUSIONS: Though the CHX and fluoride application had a limited effect (at least in this test population), one should keep in mind that it is precisely this population that requires very intensive prophylaxis, and that no antibacterial adjuvant is more effective than CHX. However, the application interval should be individually adapted to the bacteria count.

Invisalign--patient profiling. Analysis of a prospective survey.

AIM: The aim of the present prospective study was to produce a profile of those patients who are interested in treatment with the Invisalign system. PATIENTS AND METHODS: Personal data and clinical findings of 89 patients attending the Invisalign consulting hours offered by the Department of Orthodontics and Dentofacial Orthopedics, Charité Medical School were recorded. Personal data included gender, age, profession, motivation for treatment, accepted treatment duration, and initial source of information; clinical findings included anomalies of tooth position and jaw relationship as well as oral hygiene. RESULTS: Statistical analysis of the data revealed a characteristic profile: Mainly women between 20 and 29 years of age were interested in Invisalign treatment, chiefly for esthetic reasons, accepting a treatment time of 1.5 to 2.5 years. The majority of patients rejected treatment with visible appliances. 41% had been initially informed of this new treatment system by their dentist or an orthodontist, and the same percentage through different media. The standard of oral hygiene was only moderate or low in 54% of all subjects. Frontal crowding was diagnosed in 87%, and a Class II malocclusion in 49%. CONCLUSIONS: The demand for orthodontic treatment mainly among women is substantial, but many of these potential patients baulk at the esthetic impairment induced by a fixed labial appliance or the speech disturbances induced by a lingual appliance. In order to increase the acceptance of new treatment methods, the high demands placed by those concerned on esthetic and phonetic aspects should therefore be respected. With respect to oral hygiene, many patients are still in urgent need of professional instruction.

A new family of insulin-mimetic vanadium complexes derived from 5-carboalkoxypicolinates.

The reaction of 5-carboalkoxypicolinic acid (5 ROpicH, R=Me, Et, iPr, sBu; 1 a-d) with vanadyl sulfate yielded the complexes [VO(H(2)O)(5 ROpic)(2)], 2 a-d, with H(2)O and one of the picolinato ligands in the equatorial positions, and the second picolinate occupying equatorial (N) and axial (O) positions. Reaction of 1 a with [NH(4)][VO(3)] yielded [NH(4)][VO(2)(5 MeOpic)(2)], [NH(4)]-3, in which the N functions of the picolinates are trans to the doubly bonded, cis-positioned oxo groups. Complexes 1 a.H(2)O, 1 b, 1 c, 2 a.3.5 H(2)O and [NH(4)]-3.4 H(2)O have been structurally characterised. A detailed pH-potentiometric solution speciation analysis of the system VO(2+)-1 a revealed a dominance of VO(5 OMepic)(2) between pH 2 and 6, with the same coordination pattern, evidenced by EPR spectroscopy, as in the crystalline solid state. In ternary systems containing physiological concentrations of the low molecular mass biogenic binders (B) lactate, oxalate, citrate or phosphate, ternary species of general composition VO(5 MeOpic)B dominate at physiological pH, with citrate being the most effective competitor for picolinate. All of the complexes trigger glucose uptake and degradation by simian virus modified mice fibroblasts at non-toxic concentrations (<100 microM), with 2 a, [VO(2)(pic)(2)](-) and [VO(2)(dipic)](-) being at least as effective as insulin. Vanadium uptake by the cells is most effective in the case of 2 a. 2 a also effectively inhibits free fatty acid release by rat adipocytes treated with epinephrine, thus mimicking the inhibition of lipolysis by insulin.

In vitro study of the insulin-mimetic behaviour of vanadium(IV, V) coordination compounds.

A representative set of vanadium(IV and V) compounds in varying coordination environments has been tested in the concentration range 1 to 10(-6) mM, using transformed mice fibroblasts (cell line SV 3T3), with respect to their short-term cell toxicity (up to 36 hours) and their ability to stimulate glucose uptake by cells. These insulin-mimetic tests have also been carried out with non-transformed human fibroblasts (cell line F26). The compounds under investigation comprise established insulin-mimetic species such as vanadate ([H(2)VO(4)](-)), [VO(acetylacetonate)(2)], [VO(2)(dipicolinate)](-) and [VO(maltolate)(2)], and new systems and coordination compounds containing OO, ON, OS, NS and ONS donor atom sets. A vitality test assay, measuring the reduction equivalents released in the mitochondrial respiratory chain by intracellular glucose degradation, is introduced and the results are counter-checked with (3)H-labelled glucose. Most compounds are toxic at the 1 mM concentration level, and most compounds are essentially non-toxic and about as effective as or more potent than insulin at concentrations of 0.01 mM and below. V(V) compounds tend to be less toxic than V(IV)compounds, and complexes containing thio functional ligands are somewhat more toxic than others. Generally, ON ligation is superior in insulin-mimetic efficacy to OO or O/ NS coordination, irrespective of the vanadium oxidation state. There is, however, no striking correlation between the nature of the ligand systems and the insulin-mimetic potency in these cell culture tests, encompassing 41 vanadium compounds, the results on 22 of which are reported in detail here. The syntheses and characteristics of various new compounds are provided together with selected speciation results. The crystal and molecular structures of [[VO(naph-tris)](2)] [where naph-tris is the Schiff base formed between o-hydroxynaphthaldehyde and tris(hydroxymethyl)amine] are reported. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-001-0311-5.