Diffusion-weighted MRI: impact of the size of the ROI in detecting metastases in subcentimeter lymph nodes in head and neck squamous cell carcinoma.

PURPOSE: Our aim is to determine the impact of the size of ROI in detecting subcentimeter metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). Secondary aim is to determine the impact of the histopathologic grade of the primary cancer on the ADC value of the metastatic nodes. METHODS: The prospective study included 51 patients with histopathologically proven HNSCC at the primary site. Primary site includes oral cavity, oropharynx, larynx, and hypopharynx. ADC values of the lymph nodes were measured on ADC maps by placing two ROIs in the lymph nodes (0.2 cm2 in the center of the node and the whole node). Lymph nodes were dissected by levels, marked by the surgeon, and sent to the pathologist. RESULTS: By applying a smaller ROI, ADC values have greater sensitivity, specificity, NPV, PPV, and AUC in detecting metastasis compared to the ADC value of the entire node (88.0%, 80.73%, 90.7%, 75.9%, 0.912% versus 80.0%, 77.98%, 85% ,71.4%, and 0.819%, respectively) p < 0.001. Statistically significant negative correlation was established between the tumor grade and the ADC of lymph node at ROI 0.2 cm2and ROI of the whole lymph node (rho = - 0.425; p = 0.002, and rho = - 0.298; p = 0.038, respectively). CONCLUSION: ROI size affects the ADC value of the nodes. The higher histopathological grade of the primary tumor is inversely correlated with the ADC value of the lymph nodes.

ACTIVE MIDDLE EAR VIBRANT SOUNDBRIDGE SOUND IMPLANT.

The Vibrant Soundbridge represents a new approach to hearing improvement in the form of active implantable middle ear hearing device. Unlike conventional acoustic hearing aids, which increase the volume of sound that goes to the eardrum, the Vibrant Soundbridge bypasses the ear canal and eardrum by directly vibrating the small bones in the middle ear. Because of its design, no portion of the device is placed in the ear canal itself. The Vibrant Soundbridge has been approved by the FDA as a safe and effective treatment option for adults with moderate to severe sensorineural, conductive or mixed hearing losses who desire an alternative to the acoustic hearing aids, for better hearing. The paper presents a review of the active middle ear implant Vibrant Soundbridge, which has been also implanted at the Department of Otorhinolaryngology and Head and Neck Surgery, Sestre milosrdnice University Hospital Center, which is the Referral Center for Cochlear Implantation and Surgery of Hearing Impairment and Deafness of the Ministry of Health, Republic of Croatia.

TYPE II HYPOPHARYNGEAL DEFECT RECONSTRUCTION - A SINGLE INSTITUTION EXPERIENCE.

- There are several options for hypopharyngeal reconstruction depending on defect size. Reconstructive options include primary closure, local flaps, regional axial flaps or regional intestinal flaps, and free flap transfer with skin or intestinal free flaps. The preferred method of reconstruction should minimize early postoperative complications that prolong hospital stay and/or become life threatening, ensure early restoration of function and decrease donor site morbidity. The purpose of this study was to evaluate functional outcomes of different flap reconstruction methods in type II hypopharyngeal defects. In this non-randomized retrospective cohort study, data on 31 (27 male and four female) patients were collected over a 10-year period of single institution type II hypopharyngeal defect reconstructions. The following measures of functional outcome were extracted from patient medical histories: postoperative complications (flap failure, fistula formation, donor site related complications), hospital stay in days and swallowing function after 14 days, 1 month and 6 months. There were nine patients in the radial forearm free flap (RFFF) reconstruction group, seven in the jejunum reconstruction group, and 15 in the gastric tube reconstruction group. In the RFFF group, three patients experienced flap failure; in the jejunal transfer group, no donor site morbidity was observed; whereas three patients from the gastric tube reconstruction group had minor abdominal skin wound dehiscence. Out of the 3 different reconstructive methods, RFFF was most likely to fail. The mean duration of hospital stay was 22.6 days, being shortest in the RFFF group. There were no significant differences in early postoperative swallowing function among the groups. The choice of flap used for hypopharynx reconstruction should be driven by donor site factors and functional outcomes. When assessing type II hypopharyngeal defect reconstruction results, the findings of this study suggest that free jejunal flaps and gastric tubes offer superior functional results in comparison with RFFFs.

Osteoblastic Extraosseous Osteosarcoma of the Neck.

Extraosseous osteosarcoma as a primary tumor of the neck is exceedingly rare, with only a few cases reported to date. The most appropriate therapy is still under investigation. We report a case of an aggressive, right-sided, advanced-stage extraosseous osteosarcoma in a female patient. A 48-year-old woman presented with a right-sided infra-parotid mass encompassing neck regions II and III, measuring over 6 cm in craniocaudal diameter. She was initially treated by wide surgical resection. The definitive histopathologic diagnosis was osteoblastic extraosseous osteosarcoma. Computed tomography at initial presentation did not show signs of tumorous growth in other areas. The patient was treated with adjuvant chemoradiotherapy postoperatively. A local recurrence with intraspinal propagation was noted 4 months after surgery, and a second surgical attempt was made to remove the tumor. The disease recurred in the neck and spine 3 months after the second surgical procedure, and a final unsuccessful attempt at reducing the tumor mass was performed. The tumor site was reirradiated. The patient died of local disease propagation 3 months later. Extraosseous osteosarcoma of the neck is an extremely rare tumor, distinct from primary osteosarcoma of the bone, with a high rate of local recurrence and poor prognosis in advanced disease.

Proton pump (H+/K+-ATPase) expression in human larynx.

OBJECTIVE: The goal of our study was to investigate and to identify the existence of proton pump in different parts of larynx. The presence of acidic content in this area is known to be connected to several laryngeal diseases. It is mostly developed by upward recurrence of acidic gastric content, but there are some signs that the acid can be produced in the larynx as well, because of the proton pump activity in laryngeal mucosa. METHODS: The study was performed on two types of specimens: (1) 50 cadaver larynges and (2) 11 surgical larynges obtained after laryngectomy. Samples were taken from supraglottis, glottis and subglottic areas and immunohistochemistry for the beta subunit of the proton pump was done. RESULTS: The presence of proton pump was proved in seromucous glands in laryngeal supraglottic area, but it was also, for the first time, found in human chondrocytes in the thyroid and epiglottic cartilage. CONCLUSION: These new findings could encourage further research that would illuminate better the etiopathogenesis not only of laryngopharyngeal reflux, but also the pathophysiology of cartilaginous disorders.

Possible prognostic value of BORIS transcript variants ratio in laryngeal squamous cell carcinomas - a pilot study.

BORIS is a paralog of a highly conserved, multi-functional chromatin factor CTCF. Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS belongs to the "cancer/testis antigen" family normally expressed only in germ cells and aberrantly activated in a variety of tumors. The consequences of BORIS expression, relative abundance of its isoforms, and its role in carcinogenesis have not been completely elucidated. It activates transcription of hTERT and MYC, genes relevant for laryngeal carcinoma progression. In this study, BORIS expression has been analyzed at the transcriptional level by RT-PCR and protein level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell carcinomas and adjacent non-tumorous tissue. BORIS was detected in 44 % (14/32) laryngeal squamous cell carcinoma samples, while it was detected only in one normal, tumor-adjacent tissue sample. Tree based survival analysis, using the recursive partitioning algorithm mvpart, extracted the ratio of relative abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those lacking exon 7 (BORIS 7-) as an independent prognostic factor associated with disease relapse during a 5-year follow-up period. Patients having BORIS 7+/BORIS 7- ratio ≥1 had a higher rate of disease relapse than patients with BORIS 7+/BORIS 7- ratio <1. Hazard ratio for that group, based on Cox Proportional Hazard Regression, was 3.53. This is the first study analyzing expression of BORIS protein and transcript variants in laryngeal squamous cell carcinoma relative to its possible prognostic value for recurrence and overall survival.

Intrathyroid parathyroid carcinoma with intrathyroidal metastasis to the contralateral lobe: source of diagnostic and treatment pitfalls.

Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.

[ISKRA guidelines for antimicrobial prophylaxis in surgery--Croatian National Guidelines]. / Smjernice ISKRA za antimikrobnu profilaksu u kirurgiji--Hrvatske Nacionalne Smjernice.

Summary. The development of the Guidelines for perioperative prophylactic use of antimicrobial agents (further on Guidelines) was initiated by the Interdisciplinary Section for Antibiotic Resistance Control (ISKRA) of the Croatian Ministry of Health and Social Welfare in accordance with the principles of AGREE (Appraisal of Guidelines for Research and Evaluation) methodology which means that the guidelines are the result of a consensus between all involved professional societies. Guidelines were composed in order to improve antibiotic use in surgical professions. Data obtained from observational studies have shown that the use of antimicrobials in surgical professions is unsatisfactory, and since around 50% of all prescribed drugs in surgical professions refer to perioperative prophylaxis, such guidelines could significantly improve current negative trend and reduce the occurrence of infections in surgical patients as well as slow down the selection of resistant bacteria. In the introductory part of the guidelines, principles of perioperative prophylaxis are presented. The advantages and risks of prophylaxis are listed as well as factors that determine prophylaxis effectiveness. For easier orientation, surgical professions have been divided into basic surgical fields. In each field, the specificity of the field has been described followed by uniform structured tables and with every listed surgical procedure there is the most probable cause of infection, the drug of choice for prophylaxis, alternative drug, remark for particular surgical procedure and finally the grade of recommendation. The Guidelines do not cover perioperative prophylaxis in immunocompromised patients nor perioperative prophylaxis in children. The Guidelines do not cover all possible surgical interventions, but can be used as a basis for most surgical procedures performed in our hospitals. At the very end of these Guidelines, a comprehensive list of references enables all those interested to find further information and details about this topic. The revision of the Guidelines is planned in three years' time.

Magnetic resonance imaging in the diagnosis of malignant tumors of the maxillofacial region.

Magnetic resonance imaging (MRI) is a radiological imaging method that has not yet found routine application in the detection and assessment of malignant tumors of the maxillofacial region. The aim of this study was to evaluate MRI in the detection, diagnosis and differential diagnosis of malignant tumors of the maxillofacial region. This prospective study included 42 patients with clinically confirmed malignant tumors of the maxillofacial region. All patients were examined by MRI. This imaging method was evaluated for the ability to detect tumor location and to analyze dimensions and structure of the tumor, bone involvement, effect on neurovascular structures and extension to soft tissues. MRI results were compared with histopathologic and intraoperative findings as the 'gold standard' methods. MRI identified all of the clinically confirmed tumors. The sensitivity for tumor location was 94.4%, tumor necrosis 93%, hemorrhage 93.3% and bone involvement 91.4%. The specificity for tumor location was 84%, tumor necrosis 92.8%, hemorrhage 92.8% and bone involvement 85.7%. In the evaluation of soft tissue tumor extension to bone structures, MRI sensitivity and specificity was 94.4% and 88.2%, respectively. The sensitivity for perineural infiltration and tumor involvement of vascular structures was 91% and 91.6%, respectively. The specificity for perineural infiltration was 96.7% and for tumor involvement of vascular structures 88%. MRI sensitivity and specificity for intracranial extension, intraorbital propagation, extension to pterygopalatine fossa and other surrounding anatomic spaces was 93.5% and 90.9%, respectively. MRI proved advantageous for the ability to distinguish neurovascular structures from adjacent soft tissues without the use of intravenous contrast media. Study results demonstrated MRI to provide valuable information in the analysis of tumor structure, bone involvement and extension to soft tissues of malignant tumors of the maxillofacial region.

Loss of imprinting of IGF2 and H19, loss of heterozygosity of IGF2R and CTCF, and Helicobacter pylori infection in laryngeal squamous cell carcinoma.

Imprinting analyses of IGF2 and H19, loss of heterozygosity (LOH) analyses of IGF2R and CTCF and Helicobacter pylori detection, were performed on 35 human laryngeal squamous cell carcinomas (LSCC). Forty-six percent of the tumors were heterozygous for IGF2, and 54% were informative for the H19. Biallelic expression of IGF2 was observed in 33% (5 out of 15) of the tumors and in 27% (4 out of 15) of adjacent non-tumorous laryngeal tissues. H19 loss of imprinting (LOI) was observed in 24% (4 out of 17) of the tumors. For IGF2R and CTCF, 71% (25 out of 35) and 50% (17/34), respectively, of the samples were heterozygous, and LOH was detected in 12% (3 out of 25) and 6% (1 out of 17), respectively, of the tumors. H. pylori was found in 26% (9/35) of these tumors. Among them, four were informative for the imprinting analysis. The presence of H. pylori had no effect on IGF2/H19 imprinting. Only the H. pylori detection was further broadened with an additional 47 laryngeal tumors, resulting in a total final positivity of close to 16% (13 out of 82). This study represents the largest comprehensive IGF2/H19 imprinting study done to date on well-defined samples of human laryngeal carcinomas and corresponding non-tumorous tissue. For the first time, the analyses of IGF2/H19 imprinting have been broadened with LOH analyses of IGF2R and CTCF, with both of these genes acting as modulators of IGF2 and H19 activity. Although there were indications that H. pylori may be present in LSCC, we are the first to show its presence in LSCC by two direct techniques: Giemsa staining and nested-PCR.

Curcumin downregulates H19 gene transcription in tumor cells.

Curcumin (diferuloymethane), a natural compound used in traditional medicine, exerts an antiproliferative effect on various tumor cell lines by an incompletely understood mechanism. It has been shown that low doses of curcumin downregulate DNA topoisomerase II alpha (TOP2A) which is upregulated in many malignances. The activity of TOP2A is required for RNA polymerase II transcription on chromatin templates. Recently, it has been reported that CTCF, a multifunctional transcription factor, recruits the largest subunit of RNA polymerase II (LS Pol II) to its target sites genome-wide. This recruitment of LS Pol II is more pronounced in proliferating cells than in fully differentiated cells. As expression of imprinted genes is often altered in tumors, we investigated the potential effect of curcumin treatment on transcription of the imprinted H19 gene, located distally from the CTCF binding site, in human tumor cell lines HCT 116, SW 620, HeLa, Cal 27, Hep-2 and Detroit 562. Transcription of TOP2A and concomitantly H19 was supressed in all tumor cell lines tested. Monoallelic IGF2 expression was maintained in curcumin-treated cancer cells, indicating the involvement of mechanism/s other than disturbance of CTCF insulator function at the IGF2/H19 locus. Curcumin did not alter H19 gene transcription in primary cell cultures derived from normal human tissues.

[Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome]. / Hrvatske smjernice za primjenu eikozapentaenske kiseline I megestrol-acetata u sindromu tumorske kaheksije.

Among many oncological patients we can notice a substantial loss of body weight, fat and proteins with significant proinflammatory activity at the time of diagnosis. This wasting condition is well known as cancer cachexia syndrome. Anorexia is important part of this syndrome. Because cancer cachexia reduces tumor response to treatment and it is an indicator of poor prognosis, we need to start correcting these nutritional deficits at once. In the presence of cancer cachexia it is extremely difficult to achieve protein anabolism and stop the body wasting by standard nutritional formulas only. During the last few years, the use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) as anticahectic agents has been tested. These guidelines are intended to give evidence-based recommendations for the use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome. These guidelines have been developed by interdisciplinary expert group of Croatian clinicians. Based on relevant literature, we have concluded that the use of metabolic modulators such as eicosapentaenoic acid and megestrol acetate for 8 weeks may help to improve nutritional status in cachectic patients.

The role of preoperative lymphoscintigraphy in surgery planning for sentinel lymph node biopsy in malignant melanoma.

AIM: To evaluate four years of preoperative lymphoscintigraphy experience and the accuracy of sentinel lymph node biopsy in our institution in melanoma patients with various tumor thicknesses. An additional aim was to evaluate the recurrence rate related to pathohistological findings. METHODS AND PATIENTS: During the period from February 2002 to November 2005, 201 patients underwent sentinel node biopsy. Lymphoscintigraphy for identification of sentinel nodes was performed four to six hours prior to operation of the patient. Sentinel lymph node biopsy using an intraoperative hand-held gamma probe was performed in all patients, together with wide local excision of biopsy wound or primary lesion (N=56). Immediate complete basin dissection was performed in patients with sentinel node metastases. In four patients delayed complete lymph node dissection was performed after definitive histopathologic examination of sentinel nodes. The accuracy of sentinel node biopsy was determined by comparing the intraoperative rates of sentinel node identification and the subsequent development of nodal metastases in regional nodal basins in patients with tumor-negative sentinel nodes and in those with tumorpositive sentinel nodes. RESULTS: Using preoperative lymphoscintigraphy, we identified sentinel nodes in all but one of the 201 patients (99.0%), and in 248 nodal basins (1.2/patient) we observed 372 sentinel nodes (1.52 sentinels/basin; 1.8 sentinels/patient). The highest number of sentinel nodes was noticed in the groin of patients with melanoma on the lower extremities (1.5/patient), followed by the axilla (1.3/patient). Anomalous lymphatic drainage patterns were observed in 15.0% of all patients. The identification rate of sentinel nodes was 99.0% overall: 100% for the groin basins, and 98.0% for the axilla and head and neck basin. Forty-two patients (20.8%) had tumor-positive sentinel nodes. Ten patients (5.0%) had local or distant recurrences during a median follow-up of 23.1 months (range 2-46). The rate of false-negative lymphatic mapping and sentinel node biopsy as measured by nodal recurrence in patients with tumor-negative sentinel nodes was 1.3%. During the follow-up period, three of 201 patients died from other diseases and three patients died as the result of melanoma metastases, with a median follow-up of 13.5 months (range 12-22). CONCLUSION: Preoperative lymphoscintigraphy is a sensitive, inexpensive and essential method for the identification of drainage basins, determination of the number and position of sentinel nodes and their location outside the usual nodal basins. Scintigraphic findings may lead to changes in surgical management due to the unpredictability of lymphatic drainage. The low incidence of regional disease recurrence in patients with tumor-negative sentinel nodes supports the use of preoperative lymphoscintigraphy and sentinel node biopsy as a safe and accurate procedure for staging the regional nodal basin in patients with malignant melanoma.

Loss of imprinting and promoter usage of the IGF2 in laryngeal squamous cell carcinoma.

The gene for insulin-like growth factor two, IGF2 is maternally imprinted. Fifteen heterozygous samples were analyzed for the IGF2 imprinting status and promoter usage. IGF2 LOI was detected in four non-tumorous tissues and in six laryngeal squamous cell carcinoma (LSCC) tumors. There was no clear pattern of specific promoter activity in LSCC tumors and the adjacent normal tissues. P1 promoter usage was active in eight LSCCs, among them four with LOI. As it was activated in four tumors with maintenance of imprinting (MOI) and four non-tumors, we concluded that P1 promoter is not exclusively connected with IGF2 LOI in LSCC.

Speech and voice analysis after near-total laryngectomy and tracheoesophageal puncture with implantation of Provox 2 prosthesis.

Vocal characteristics were compared in two groups of patients who were operated on due to laryngeal cancer. One group was composed of patients after near-total laryngectomy and the other after total laryngectomy followed by tracheoesophageal puncture with implantation of Provox 2 prosthesis. Acoustic analysis was carried out using the EZ Voice Plus program and included the following parameters: fundamental frequency, jitter, shimmer, harmonic to noise ratio, range of fundamental frequency, maximal phonation time and intensity.

Modified alar swing procedure in saddle nose correction.

Reconstruction of the saddle nose may involve the use of different augmentation materials, from autogenous bone and cartilage to alloplastic materials. The most important problems when considering the choice of reconstructive technique, besides underlying pathology and expected result, include: long-term stability, donor morbidity, tendency of the implant to infection, extrusion, and resorption. The use of the lateral crura of the lower lateral cartilages as dorsal onlay was reserved for the corrections of minor supratip depressions (flying wing and alar swing procedure). The authors suggest the use of pedicled flaps of cephalic portions of lateral crura as dorsal septal strut, which may increase the profile line more than dorsal onlay. Reconstruction is performed using open rhinoplasty approach. Pedicled flaps of the cephalic portions of lateral crura are transfixed in the sagittal plane and, following separation of upper lateral cartilages and medial crura, placed on the dorsum of nasal septum. Upper laterals are sutured to newly formed cartilaginous dorsum, or a new bridge is created using conchal cartilage. Columellar strut may be formed of the septal cartilage. Authors have performed such corrections in 15 patients with good long-term functional and aesthetic results.

Use of skin staplers in head and neck surgery: prospective clinical study.

OBJECTIVE: To compare the advantages and disadvantages of skin staplers versus conventional sutures in head and neck surgery. SUBJECTS: Fifty consecutive patients who underwent extensive surgery in the head and neck area were included in this prospective trial. METHODS: Patients were randomized into two equal groups: one group had their wounds closed with staplers and the other with monofilament sutures. The main outcome measures were speed of suturing, wound healing and cosmetic result, complications, and cost of either method. RESULTS: Cosmetic results were good in both groups. Neither group had any complications. Wound closure speed was 18.9 +/- 1.4 cm/min when using skin staplers and 1.9 +/- 0.4 cm/min for conventional suturing (p < .001). CONCLUSION: Skin staplers significantly reduce wound closure time and yield similar cosmetic results with no complications and with only a slightly higher cost of suturing material.