Neuromonitoring of recurrent laryngeal nerves in thyroid surgery comparative study of visualisation and electrophysiology methods.

Úvod: Poranění zvratného nervu je jedna z nejzávažnějších komplikací chirurgie štítné žlázy, chirurgie příštítných tělísek a chirurgie krčních obratlů. V literatuře se popisuje poranění zevní větve hrtanových nervů jako méně časté. Tato komplikace je natolik vážná, že může vést k invalidizaci hlasových profesionálů (učitelů, herců, zpěváků, profesionálních řečníků a manažerů). Současná klinická praxe je spojena se zvýšeným úsilím o peroperační ochranu funkce zvratných nervů využíváním elektrofyziologické monitorace funkce inervace hrtanu a současné vizualizace zvratných nervů. Metody: Design studie je prospektivní observační. Ze souboru 100 po sobě jdoucích operací byly chirurgy náhodně vytvořeny dvě skupiny: Skupina A - s použitím neuromonitoringu (IONM) a skupina B - identifikace a vizualizace zvratného nervu (NLR) bez IONM. Jeden tým chirurgů byl složen z experta (více než 1000 provedených operací) a začínajícího chirurga (méně než 100 operací) a druhý ze dvou zkušených chirurgů (jeden více než 150 operací a druhý více než 500 operací). Každý tým byl zapojen do operací několikrát v týdnu. Porovnání bylo provedeno statistickými metodami a pomocí indexu poranění zvratného nervu (recurrent nerve injury - IRI). Cílem studie je porovnat incidenci parézy zvratných nervů při využití neuromonitorace (IONM) a využití peroperační vizualizace anatomicky neporaněného nervu dvěma týmy chirurgů. Výsledky: Bylo analyzováno 100 operací, respektive 50 operací ve skupině A a 50 ve skupině B. Skupina A zahrnovala 43 totálních thyreoidektomií a 7 hemithyreoidektomií a byly zjištěny dvě dočasné jednostranné parézy. Skupina A měla IRI=1,075. Skupina B zahrnovala 48 totálních thyreoidektomií a 2 hemithyreoidektomie. V této skupině byly zjištěna také dvě jednostranné dočasné parézy zvratného nervu. Skupina B měla IRI=1,02. Uvedené hodnoty IRI tak charakterizují asymetrické soubory, i tato drobná asymetrie je ve výsledku hodnoty patrna. Celková incidence poranění zvratných nervů v celém souboru operovaných sledovaného roku, ve kterém byl výběr pacientů dle metodiky této práce, byla 1,3 %. V souboru bylo 16 dočasných a 4 permanentní parézy zvratného nervu ve všech případech na jedné straně. Ve sledovaném období nebyla zjištěna ani jediná oboustranná paréza trvalá ani dočasná. Index IRI pro operace štítné žlázy v uvedeném období byl 2,26. Tento soubor byl srovnáván se soubory skupiny A a skupiny B a výsledky nevykazují statisticky významné rozdíly na hladině významnosti 1 % (p=0,01). Závěr: Studie neprokázala statisticky významné rozdíly incidence poranění zvratného nervu (trvalá jednostranná paréza) v závislosti na chirurgické technice bez využití IONM a s využitím IONM prováděných chirurgem s rozdílnou zkušeností v chirurgii štítné žlázy. Studie prokázala, že IONM může pomoci vyrovnat handicap u začínajících a méně zkušených chirurgů a omezit incidenci morbidity zvratného nervu v chirurgii štítné žlázy.

Morbidity and mortality of parathyroid surgery - a retrospective analysis.

INTRODUCTION: The incidence of parathyroid - glandula parathyreoideae (PTG) diseases has been increasing worldwide. Unlike benign tumours, the incidence of malignant PTG tumours is rather a rare diagnosis. The morbidity of parathyroid surgery is associated with surgical removal of one or more pathologically altered parathyroid glands, particularly parathyroid adenoma associated with primary hyperparathyroidism (HPPT), but also hyperplasia associated with secondary or tertiary HPPT, and last but not least, HPPT due to parathyroid cancer. METHODS: A retrospective statistical analysis was performed in the set of patients undergoing surgery for a parathyroid disorder at the Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine, Charles University and Military University Hospital in Prague in 2013-2019 (7-year period). In this period, 127 procedures were performed. The incidences of morbidity, mortality, complications and lethality were analysed. RESULTS: Parathyroid surgery was performed in 20 male and 107 female patients. The mean age was 54.7 years, and the morbidity expressing recurrent laryngeal nerve (RLN) palsy was 0.7% of the nerves exposed during the procedure. The incidence of permanent normal postoperative calcaemia was 98.43%, demonstrated by a decrease in serum parathyroid hormone (PTH) levels. In 12 cases, this state was achieved only after a surgical revision (primary procedure for primary HPPT in 2 cases; 10 patients came for surgical revision with secondary or tertiary HPPT from other centres). Decreased PTH levels were demonstrated intraoperatively in 12.6% patients using the so-called PTH assay (a rapid serum PTH assay). Surgery for secondary or tertiary hyperparathyroidism was done in 33 patients (26% procedures). PTG surgery lethality (mortality) was divided into perioperative mortality within 24 hours from the procedure and early mortality within 120 hours. Lethality related to PTG surgery was 0.0% including patients undergoing the surgery while being in a dialysis programme and those with kidney transplant. CONCLUSIONS: Surgery is always associated with complications, with morbidity and mortality. Experience of endocrinology surgeons of all specialties is reflected in a very low incidence of RLN injuries and in sufficient oncological, or respectively, surgical radicality. This, in connection with other medical fields of endocrinology, nephrology, transplantology, nuclear medicine and oncology, allows a safe and effective treatment of all PTG disorders with a good prognosis for the patients. In those with secondary or tertiary HPPT, it not only improves their quality of life, which was not explored in our study, but in many cases it is an essential step for listing the patient for the transplant surgery. The current level of experience in the field of parathyroid carcinoma does not enable us to formulate any conclusions in terms of prognosis which should be considered as very serious in all cases.

Nonfunctional parathyroid cancer a case report.

INTRODUCTION: Parathyroid cancer is a rare endocrine malignancy. These tumors are typically functional, causing severe hypercalcemia due to primary hyperparathyroidism. Nonfunctional parathyroid cancer with normal serum calcium and parathyroid hormone levels is extremely rare. The disease is usually indolent but progressive with a tendency to metastasize. It is very difficult to diagnose this malignancy. The definitive diagnosis is made by histopathological examination. Radical surgery with ipsilateral lobectomy and en bloc neck dissection is considered to be the most appropriate therapeutic approach. There is no evidence of efficiency of adjuvant cancer therapy and its indication has not been defined. Disease recurrence is common. CASE REPORT: We report the case of a 26-year-old female patient who underwent left hemithyroidectomy for growth progression of a hypoechoic lesion behind the left thyroid lobe detected by ultrasonography. Preoperative cytology and imaging assessments were not suspicious for malignancy. Serum parathyroid hormone and calcium levels were normal. The diagnosis of nonfunctional parathyroid carcinoma was determined based on histopathological examination. No further surgery or adjuvant therapy was indicated. No signs of recurrence or generalization have been observed at 36 months after the surgery. CONCLUSION: Nonfunctional parathyroid cancer is extremely rare. In many cases, the diagnosis is made in advanced stages of the disease. No formal classification or treatment protocol has been established so far. A new staging system has been proposed in the 8th edition of AJCC/UICC. Early detection, radical surgery and close follow-up are crucial aspects to affect the mortality and morbidity of patients with this type of malignancy.

Definition of stereotactic body radiotherapy: principles and practice for the treatment of stage I non-small cell lung cancer.

This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft für Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy.

Influence of intraoperative radiotherapy (IORT) on perioperative outcome after surgical resection of rectal cancer.

BACKGROUND: Intraoperative radiotherapy (IORT) for locally advanced or recurrent rectal cancer as an integral part of multimodal treatment might be an option to reduce local cancer recurrence. The aim of the present study was to determine the influence of IORT on the postoperative outcome and complications rates in the treatment of patients with adenocarcinoma of the rectum in comparison to patients with rectum resection only. METHODS: A total of 162 patients underwent operation for International Union against Cancer stage III/IV rectal cancer or recurrent rectal cancer at our surgical department between 2004 and 2012. They were divided into two groups depending on whether they received IORT or not. General patient details, tumor, and operation details, as well as perioperative major and minor complications, were registered and compared. RESULTS: Of the 162 patients treated for stage III/IV rectal cancer, 52 underwent rectal resection followed by IORT. Complication rates were similar in the two groups. Operative time was significantly longer in the IORT group (248 ± 84 vs 177 ± 68 min; p < 0.001). No significant differences were found concerning anastomotic leakage rate, hospital stay, or wound infection rate. CONCLUSIONS: Intraoperative radiotherapy appears to be a safe treatment option in patients with locally advanced or recurrent rectal cancer with acceptable complication rates. The effect on local recurrence rate has to be estimated in long-term follow-up.

Treatment planning after hydrogel injection during radiotherapy of prostate cancer.

PURPOSE: Imaging for treatment planning shortly after hydrogel injection is optimal for practical purposes, reducing the number of appointments. The aim was to evaluate the actual difference between early and late imaging. PATIENTS AND METHODS: Treatment planning computed tomography (CT) was performed shortly after injection of 10 ml hydrogel (CT1) and 1-2 weeks later (CT2) for 3 patients. The hydrogel was injected via the transperineal approach after dissecting the space between the prostate and rectum with a saline/lidocaine solution of at least 20-ml. Hydrogel volume and distances between the prostate and rectal wall were compared. Intensity-modulated radiotherapy (IMRT) plans up to a dose of 78 Gy were generated (rectum V70 < 20 %, rectum V50 < 50 %; with the rectum including hydrogel volume for planning). RESULTS: A mean planning treatment volume of 104 cm(3) resulted for a prostate volume of 37 cm(3). Hydrogel volumes of 30 and 10 cm(3) were determined in CT1 and CT2, respectively. Distances between the prostate and rectal wall at the levels of the base, middle, and apex were 1.7 cm, 1.6 cm, 1.5 cm in CT1 and 1.3 cm, 1.2 cm, 0.8 cm in CT2, respectively, corresponding to a mean decrease of 24, 25, and 47 %. A small overlap between the PTV and the rectum was found only in 1 patient in CT2 (0.2 cm(3)). The resulting mean rectum (without hydrogel) V75, V70, V60, V50 increased from 0 %, 0 %, 0.6 %, 10 % in CT1 to 0.1 %, 1.2 %, 6 %, 20 % in CT2, respectively. CONCLUSION: Treatment planning based on imaging shortly after hydrogel injection overestimates the actual hydrogel volume during the treatment as a result of not-yet-absorbed saline solution and air bubbles.

Quality of life after intensity-modulated radiotherapy for prostate cancer with a hydrogel spacer. Matched-pair analysis.

BACKGROUND: Hydrogel spacer is an innovative method to protect the rectal wall during prostate cancer radiotherapy. Clinical effects are not well known. METHODS: Patients have been surveyed before, at the last day, and 2-3 months after radiotherapy using a validated questionnaire (Expanded Prostate Cancer Index Composite). Median dose to the prostate in the spacer subgroup (SP) was 78 Gy in 2 Gy fractions. The results were independently compared with two matched-pair subgroups (treated conventionally without spacer): 3D conformal 70.2 Gy in 1.8 Gy fractions (3DCRT) and intensity-modulated radiotherapy (IMRT) 76 Gy in 2 Gy fractions. There were 28 patients in each of the three groups. RESULTS: Baseline mean bowel bother scores were 96 points in all subgroups. Similar mean changes (SP 16, 3DCRT 14, IMRT 17 points) were observed at the end of radiotherapy. The smallest difference resulted in the spacer subgroup 2-3 months after radiotherapy (SP 2, 3DCRT 8, IMRT 6 points). Bowel bother scores were only significantly different in comparison to baseline levels in the spacer subgroup. The percentage of patients reporting moderate/big bother with specific symptoms did not increase for any item (urgency, frequency, diarrhoea, incontinence, bloody stools, pain). CONCLUSION: Moderate bowel quality-of-life changes can be expected during radiotherapy irrespective of spacer application or total dose. Advantages with a spacer can be expected a few weeks after treatment.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

Hyperbaric oxygen therapy in idiopathic sudden sensorineural hearing loss (ISSNHL) in association with combined treatment.

The main basic effect of hyperbaric oxygenation (HBO2) on the human body, in our study, was an increased partial pressure of oxygen resulting from an increased amount of oxygen dissolved in plasma. Thus the plasma can become capable of carrying enough oxygen to meet the needs of the body's tissues. From 1 January 2004 to 31 December 2007, a total of 61 patients (62 ears) received medical treatment at the ENT clinic of the 3rd Faculty of Medicine, Charles University, and at the Central Military Hospital in Prague. Treatment consisted of a combination of vasodilatation infusion treatment and HBO2 therapy. The results were evaluated in a retrospective study. The overall percentage of patients showing improvement was 59.7%. However, for those patients who started HBO2 treatment within 10 days of onset, complete recovery, or significant improvement was noted in 65.9%. In contrast, patients who started treatment after 10 days of onset, improvement was noted in only 38.9%. NMR examination revealed that two patients had vestibular schwannoma (also known as acoustic neuroma).

Increased expression of chemokine receptors CCR1 and CCR3 in nasal polyps: molecular basis for recruitment of the granulocyte infiltrate.

Inflammatory processes play an important role in the development of nasal polyps (NP), but the etiology and, to a high degree also, the pathogenesis of NP are not fully understood. The role of several cytokines and chemokines such as eotaxins, IL-4, IL-5, IL-6, IL-8, and RANTES has been reported in NP. Herewith, we investigated the expression and pattern of distribution of chemokine receptors CCR1 and CCR3 in nasal polyps. Immunohistochemical detection was carried out in frozen sections of biopsies from 22 NP and 18 nasal mucosa specimens in both the epithelial and stromal compartments. Fluorescence microscopy and computerized image analysis revealed a statistically significant increased number of CCR1 (45.2 ± 2.8 vs. 15.1 ± 1.9, p < 0.001)-positive as well as CCR3 (16.4 ± 1.4 vs. 9.7 ± 1.1, p < 0.001)-positive cells in the stroma of NP compared to nasal mucosa. In comparison to healthy nasal mucosa, increased positivity of CCR3 was detected in the epithelial compartment of NP. Our data suggest that increased expression of CCR1 and CCR3 chemokine receptors may, in accord with various chemokines, contribute to the pathogenesis of nasal polyposis by facilitating increased migration and prolonged accumulation of inflammatory cells, e.g., eosinophils, in the inflammatory infiltrate of NP.

Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and innate immune mechanisms in pathogenesis of nasal polyposis.

Nasal polyps (NP), edematous projections of nasal mucosa (NM), are characterized by an inflammatory cellular infiltrate, however, little is known about etiopathogenesis of NP. Both innate immune mechanisms leading to activation of NF-kappaB and homeostasis of epithelial cells were implicated in the pathogenesis of NP. In this study we investigated the expression of insulin-like growth factor-1 receptor (IGF-1R) and inducible nitric-oxide synthase (iNOS) in NP compared to healthy NM in both the epithelial and stromal compartments. Using immunohistochemistry, frozen tissue sections of NP from 18 patients, and mucosal biopsy specimens of the inferior turbinate from 17 subjects were stained for IGF-1R and iNOS markers. Fluorescence microscopy and computerized image analysis revealed low numbers of IGF-1R-positive cells in all specimens. However, substantially increased numbers of IGF-1R-positive cells were found in NP compared to NM both within the epithelium (1.63 vs. 0.43) and stroma (3.27 vs. 1.03). Positivity for iNOS was detected within the epithelium of NP compared with NM. Numbers of iNOS-positive single cells were highly increased in NP vs. NM in both epithelial (3.83 vs. 1.08) and stromal (4.96 vs. 2.67) compartments. An increased iNOS expression within the epithelial layer as well as increased number of iNOS- and IGF-1R-positive cells in NP was observed. This suggests that innate immune mechanism, and to a lesser extent also growth and homeostasis of epithelial cells, may play a role in formation of NP.

5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of chemotherapy-induced emesis.

This study evaluated the relationship between prechemotherapy cortisol and 5-hydroxyindoleacetic acid (5-HIAA) excretion and chemotherapy-induced emesis. The urinary excretion of cortisol and the serotonin metabolite 5-HIAA in the night before chemotherapy administration were measured in 28 and 49 female patients receiving > 300 mg m-2 carboplatin. Vomiting and nausea were documented over a 3 day observation period. Lower basal cortisol excretion was significantly correlated with vomiting with or without nausea occurring within the observation period. 5-HIAA showed only a weak correlation with emesis on days 1-3, but low 5-HIAA excretion was correlated with a higher proportion of patients vomiting on days 2-3 following chemotherapy. Low basal cortisol excretion might be useful as a predictor for chemotherapy-induced emesis and therefore should be evaluated prospectively in future studies.

5-Hydroxyindoleacetic acid excretion following combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil plus ondansetron compared to ondansetron alone.

The aim of the work was to evaluate the impact of cyclophosphamide and ondansetron on serotonin metabolism measured by urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion. The pattern of urinary 5-HIAA excretion was analysed within 24 h following cyclophosphamide, epirubicin and 5-fluorouracil (FEC) chemotherapy (n = 14), ondansetron as single agent (n = 31), and in a control group (n = 62). 5-HIAA was measured by a fluorescence/polarisation immunoassay. Both FEC and ondansetron alone induced a significantly higher 5-HIAA increase following the first 12 h after drug administration when compared to the control group. The comparison of quantitative variables of 5-HIAA excretion between FEC and ondansetron failed to reveal any statistical differences. Cyclophosphamide-based chemotherapy is associated with only minor increases of 5-HIAA excretion. Analysis of 5-HIAA excretion does not help in the description of the pathophysiology of cyclophosphamide-induced emesis. In contrast to experimental data, serotonin 3 receptor antagonism with ondansetron induces an increase of 5-HIAA excretion in humans.

The relationship between parameters of serotonin metabolism and emetogenic potential of platinum-based chemotherapy regimens.

Evaluation of the relationship between parameters of serotonin (5-HT) metabolism and emesis in platinum-based chemotherapy. Female patients receiving chemotherapies containing either cisplatin (35 patients; 80 courses) or carboplatin (65 patients; 102 courses) were recruited. Recording of emesis and measurements of urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was performed over 3 days. Comparisons were performed for single-agent cisplatin (DDP) versus single-agent carboplatin (CBDCA), single-agent high-dose DDP (> or = 75 mg/m2) versus high-dose DDP combined with cyclophosphamide, high-dose versus low-dose DDP (< or = 50 mg/m2), and single-agent CBDCA versus a combination with alkylating agents. Cisplatin induced both a significantly higher frequency of emesis and a significantly higher increase of 5-HIAA excretion than carboplatin. The velocity of 5-HIAA increase may correlate better with emetogenic potential than peak 5-HIAA excretion levels. The increase of 5-HIAA excretion induced by cisplatin was limited to day 1. Higher cisplatin doses showed both a higher emetogenic potential and a more pronounced increase in urinary 5-HIAA on day 1. No significant difference was found when single-agent cisplatin was compared with cisplatin combined with cyclophosphamide. In contrast, a combination of carboplatin with alkylating agents induced a larger increase in urinary 5-HIAA and showed a higher emetogenic potential than single-agent carboplatin. Low-dose cisplatin induced less emesis than carboplatin combination therapy, but induced a larger increase in urinary 5-HIAA. Our findings provide evidence for a relationship between emetogenic potential and patterns of 5-HIAA excretion following platinum-based chemotherapy.