Anterior open bite - diagnostics and therapy.

An anterior open bite (AOB) is an occlusal disorder that causes the patient both an aesthetic and functional handicap. The lower third of the face is disproportionately larger. Patients are unable to properly occlude with the anterior part of dental arch and occlusion only happens in the premolar and/or molar regions. An anterior open bite may be the result of anatomical anomalies. Long term stability as well as an immediate outcome of the surgery depends on the choice of a suitable treatment strategy. In this article, we review options of AOB treatment, from classical orthodontic treatment to current combined orthodontic and surgical approach with a benefit of an anchor system.

INDICATION AND IMPORTANCE OF RECONSTRUCTIVE SURGERIES OF FACIAL SKELETON IN MAXILLOFACIAL SURGERY: REVIEW.

Malignant head and neck tumors belong among common diseases and their incidence constantly rises. In the Czech Republic, the proportional representation of orofacial tumors ranges around 2% of the total number of malignancies. Rational treatment of these tumors is complex and long. In the course of therapeutic planning, you have to consider the age of the patient and the stage of the disease including the presence of distant metastases. Removal of the tumor with a sufficient safety margin and an eventual treatment of the relevant lymphatic system according to the type of the tumor is an important prerequisite for the success of the surgical therapy. Reconstructive procedures in maxillofacial oncosurgery presume good interdisciplinary cooperation and a high professional preparedness of the surgical and nursing team. Selection of the right patient is also very important with regard to the risks of both local and systemic postoperative complications. Use of the free flap techniques is currently the gold standard, but it is also necessary to master pedicled flap techniques, whose advantages lie in simpler technique and often better aesthetic results. At the same time, we have to realize that even traditional, classical reconstructive procedures using prosthetic replacements can still represent the ideal solution in many cases.

HIRUDOTHERAPY IN RECONSTRUCTIVE SURGERY: CASE-REPORTS AND REVIEW.

Medicinal leeches (Hirudo medicinalis, Hirudo verbana) have been used in the field of medicine to treat various diseases for thousands of years. Popularity of their use changed over time and in Europe, it peaked at the beginning of the 19th century. In modern medicine, application of leeches on flaps with venous congestion was first used and described by Deganc and Zdravic in 1960. A certain renaissance of leech use is currently taking place, especially in the field of reconstructive surgery. In general, use of leeches is indicated during critical post-operative period, in which the microcirculation and veins are incapable of sufficient drainage of venous blood, which can lead to stagnation of circulation in tissues at all levels, clinically manifested as a change in color and turgor of the flap. If this venostasis is not recognized in time and treated adequately, tissue necrosis can develop. Medicinal leeches can be used in venous drainage disorders after a replantation of fingers, auricles, lips and parts of the nose. In head and neck reconstructive surgery, there are many studies that confirm the success rate of hirudotherapy in hematoma evacuation or in dealing with complications after scalp replantation and transfers of free and pedicled flaps. Leech application therapy can also be indicated as a part of non-surgical methods that improve conditions of the venous system.

Pedicled pectoralis major flap in head and neck reconstruction - technique and overview.

The pedicled pectoralis major flap was the original workhorse flap for head and neck reconstruction. Over time, it became the secondary choice for oropharyngeal reconstruction with the implementation of free-soft tissue transfers. Nowadays, a polymorbid patient is primarily indicated for pedicled pectoralis major flap reconstruction, other indications include combinations of pedicled pectoralis major flap with free microvascular flap, salvage reconstruction due to complications, salvage reconstruction due to free flap failure and salvage reconstruction due to recurrent or extended primary disease. Pedicled pectoralis major flap can be successfully used for specific oropharyngeal defects, even primary resections, especially for less cooperative patients and patients after extensive neck dissection. Improving the flap harvesting techniques can reduce undesired complications in specific cases of oropharyngeal reconstruction. Flap morbidity in these cases remains comparable to morbidity of patients who had undergone free flap reconstruction. Pedicled pectoralis major flap remains valid reconstruction tool that should be included in the armamentarium of each surgeon dealing with reconstruction of the head and neck.

Pedicled pectoralis major flap in head and neck reconstruction - our experience.

INTRODUCTION: The pedicled pectoralis major flaps are still harvested and mainly indicated for reconstruction in the polymorbid patient. Other indications are combinations of pedicled pectoralis major flaps with free microvascular flap, salvage reconstruction following complications, free flap failure and recurrent or extended primary disease. MATERIALS AND METHODS: We describe the pedicled pectoralis major flap in 18 patients operated on at the Department of Oral and Maxillofacial Surgery, Olomouc from 1st January 2014 to 1st December 2016. RESULTS: Fifteen oropharyngeal defect reconstructions were performed using pedicled pectoralis major flap (including 1 submandibular defect of the neck). Indications were primary resection in polymorbid patients in 10 cases and recurrent diseases after previous neck dissection and radiotherapy in 5 cases. Pedicled pectoralis major flap was used for secondary reconstruction in 3 cases. Complications occurred in 50 % of patients, 28 % were major and 22 % minor. Major complications included a total flap failure (defect was successfully treated with free tissue transfer of latissimus dorsi myocutaneous flap) in 1 case, plate exposure in 2 cases, large dehiscence and large hemorrhage 1 case each. Minor complications included only small dehiscences (22 %). One was associated with fluidothorax after rib harvesting (6%). There were no cases of neck contracture or supraclavicular bulge. CONCLUSION: Even today, usage the pedicled pectoralis major flap in head and neck reconstruction surgery cannot be considered as an obsolete reconstructive procedure that has been completely replaced by a free microvascular flap. Innovations of flap harvesting techniques and high rate of flap survival are the main reasons why pedicled pectoralis major flap can still be primarily indicated for high-risk patients, non-cooperative patients and also for patients with extensive neck dissection. The pedicled pectoralis major flap has been the first choice in salvage surgery, in cases of a complication or free flap failure or a recurrence of a primary disease.

[Cystic lesions of the pancreas : Differential diagnostics and treatment]. / Zystische Raumforderungen des Pankreas : Differenzialdiagnostik und Therapie.

Cystic space-occupying lesions of the pancreas represent incidental findings in most cases. As there is a potential risk of malignant transformation further evaluation of the lesions as well as a follow-up of these patients is usually recommended. Before this work-up is initiated the clinical situation of the patient as a whole and comorbidities, age and personal preferences have to be taken into account. So far there are no biomarkers that reliably predict the risk of malignant transformation. Imaging by magnetic resonance tomography (MRI) in combination with magnetic resonance cholangiopancreatography (MRCP) is more accurate than computed tomography to identify worrisome features. During follow-up, endoscopic ultrasound (EUS) can be used as complementary method to MRI/MRCP. Using contrast enhancement or endoscopic fine needle aspiration (EUS-FNA) may influence the therapeutic strategy in some patients. Whereas for some cystic pancreatic lesions consensus has been reached, varying recommendations exist for intraductal papillary mucinous neoplasms (IPMN). There is consensus that in main-duct as well as in mixed-type IPMN surgery is recommended. The management of branch-duct type IPMN, however, remains controversial. A multidisciplinary expert panel including gastroenterologists, visceral surgeons, radiologists and pathologists is essential to discuss all cases of patients with cystic pancreatic lesions and to guarantee an optimal, patient-centered treatment recommendation.

[Metabolic disorders as paraneoplastic syndromes]. / Metabolische Entgleisungen als paraneoplastische Syndrome.

Paraneoplastic syndromes are characterized by the tumor-induced release of peptide hormones and/or the initiation of immune phenomena, which elicit clinical changes and alterations in laboratory parameters independent of the tumor size and spread. In addition to neurological, endocrinal and rheumatological phenotypes, metabolic alterations play a special role in the clinical routine as they commonly present with acute symptoms in an emergency situation and necessitate immediate diagnosis and prompt initiation of treatment. Metabolic alterations within the framework of malignant diseases should be treated in a multidisciplinary team and it is often necessary to perform monitoring and treatment in an intensive care unit. This article focuses on the diagnostic and therapeutic options for metabolic disorders due to paraneoplastic syndromes, such as hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia and a special variant of tumor-induced metabolic disorders due to tumor lysis syndrome.

Relevance of dihydropyrimidine-dehydrogenase and thymidylate-synthase in patients with pancreatic neuroendocrine neoplasms treated with 5-FU-based chemotherapy.

BACKGROUND: Chemotherapy with 5-FU and Streptozotocin (STZ) is recommended as first-line treatment in patients with metastatic pancreatic neuroendocrine neoplasms (PNEN). However, data about biomarkers involved in the 5-FU metabolism to predict response are still limited. OBJECTIVES: Evaluation of clinicopathological features and potential predictive and prognostic markers of patients with PNEN treated with 5-FU based regimens. PATIENTS AND METHODS: We retrospectively analyzed 41 patients with PNEN who were treated at the University Hospital Marburg between 2000 and 2013. Dihydropyrimidine-Dehydrogenase (DPD) and Thymidylate-Synthase (TS) expression was correlated with treatment response in 19 patients who had available tumour tissue and response data. The median overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. RESULTS: The median PFS in patients receiving 5-FU/STZ was 17 months with a median OS of 50 months. Objective response rate (ORR) and disease control rate (DCR) were 32% and 73%, respectively. Biochemical response (p = 0.005) and high DPD expression (p = 0.018) were predictive markers of response to 5-FU-based chemotherapy. Univariate analysis identified Ki-67 > 10%, no biochemical response, positive 5-HIAA levels and TS deficiency as independent risk factors for shorter PFS. Moreover, performance status (PS) ≥1 was an independent risk factors for impaired OS. CONCLUSIONS: DPD expression and biochemical response represent promising predictive biomarkers for response to 5-FU based chemotherapy. Moreover, Ki-67, PS and TS are independent prognostic markers of OS and PFS in patients with PNEN.

[HPV in etiology of orofaryngeal cancer according to sexual activity]. / HPV v etiologii orofaryngeálního karcinomu a jeho vztah k sexuální aktivite

OBJECTIVE: The objective of this study is to confirm or exclude the presence of the HPV in oral cavity according to sexual activity. DESIGN: Prospective not blinded study. SETTING: Clinic of Oral and Maxillofacial Surgery, Clinic of Obsterics and Gynecology, Department of Microbiology, Medical Faculty Palacky University and University Hospital Olomouc. METHODS: The patients were examined during the screenig for cervix carcioma at the Clinic of Obsterics and Gynecology. After filling the Consent Form and the questionnaire for possible exposure to potentional risk the swabs from cervix and mouth were sampled. The samples have been processed at the Department of Microbiology by the Real Time PCR. RESULTS: The results have not confirmed the relation between sexual practices and infection of oral cavity by the HPV. CONCLUSION: Our results correspond with certain authors. There is unclear correlation between total number of sexual partners and infection of mouth with the HPV. Nevertheless the HPV related tumors have been proven - especially in the oropharynx- but the way how the infection enters the mouth remains still unclear, according to us.

CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling.

Many solid cancers including pancreatic ductal adenocarcinoma (PDAC) are characterized by an extensive stromal reaction that is accompanied by infiltrating tumor-associated macrophages (TAMs). The role of TAMs in malignant tumors is only partially understood. Previously, we identified the transcription factor CUX1 as an important mediator of tumor progression in PDAC. Interestingly, we found that CUX1 is highly expressed not only in tumor cells but also in TAMs. On the basis of these data, we aimed to elucidate the effects of CUX1 in TAMs in vitro and in vivo. We analyzed the effects of CUX1 on cytokine expression using overexpression and knockdown strategies. The cytokine regulation by CUX1 was further assessed by reporter assays, DNA pulldown experiments and chromatin-immunoprecipitation. CUX1 expression in TAMs was analyzed in human pancreatic cancer tissues and in a genetic mouse model. Immunohistochemical analysis revealed strong expression levels of CUX1 in a distinct subset of TAMs in human PDAC tissues. Furthermore, its expression increased during tumor progression in a genetic mouse model of PDAC. Profiling experiments showed that CUX1 downregulates several NF-κB-regulated chemokines such as CXCL10, which have been associated with M1 polarization and inhibition of angiogenesis and tumor progression. We could demonstrate that CUX1 interacts with NF-κB p65, leading to reduced binding of NF-κB p65 to the chemokine promoters. In addition, CUX1 reduces acetylation of NF-κB p65 at K310 by recruiting HDAC1. Functionally, CUX1 expression in TAMs antagonizes T-cell attraction and enhances angiogenesis in vitro. We identified CUX1 as an important modulator of the TAMs phenotype and function by modulating NF-κB-dependent cytokines.

Ultrasound-guided botulinum toxin injection to treat a parotid fistula following gunshot injury.

Parotid fistula is a rare but very distressing sequelum of post-operative or traumatic injuries. The management of these injuries has been reported in the literature previously and techniques employed include pressure dressings, surgery and more recently botulinum toxin A (BTA) injections. We present a patient who developed a parotid fistula as a late complication of an extensive gunshot injury to the face with subsequent successful management with ultrasound-guided intraglandular injections of BTA. This case demonstrates that the BTA injection is an effective and safe method under ultrasound guidance and should considered as a first-line treatment option for the treatment of salivary fistulas.

nab-Paclitaxel: novel clinical and experimental evidence in pancreatic cancer.

The past few decades have seen virtually no treatment advances for patients with metastatic pancreatic cancer. Clinical hallmark features of pancreatic ductal adenocarcinoma (PDA) include late symptom onset, invasive growth, early liver and lymph node metastasis, and resistance to available chemotherapies. nab-Paclitaxel (Abraxane®) is generated through high-pressure homogenization of human albumin and conventional paclitaxel resulting in non-covalently bound, water-soluble albumin-paclitaxel particles with an approximate diameter of 130 nm. Results from the recently completed Metastatic Pancreatic Adenocarcinoma Trial (MPACT) (phase III trial) showed a significant survival benefit for patients treated with nab-paclitaxel in combination with gemcitabine, and this treatment regimen is currently being implemented in national and international guidelines for PDA patients. Therefore, this regimen provides a much needed vantage point of attack for this recalcitrant tumor offering potential new hope for our patients. Mechanisms such as stromal depletion, selective intratumoral accumulation, synergism with gemcitabine metabolism and secreted protein acidic and rich in cysteine (SPARC) mediated anti-tumor activity have been suggested for nab-paclitaxel. This review discusses the clinical and experimental advances of nab-paclitaxel in pancreatic cancer.

[A 59-year-old patient with recurrent flushes and bland hepatic cyst]. / 59-jähriger Patient mit rezidivierendem Erröten bei blander Leberzyste.

A 59-year-old patient was admitted to hospital with recurrent flush symptoms and pathologically elevated 5-hydroxyindoleacetic acid (5-HIAA) levels in urine. A known cystic lesion of the liver which had been followed for years by ultrasound examinations and was regarded as a bland hepatic cyst was identified as a metastasis of a neuroendocrine neoplasm of the ileum. In two sequential surgical interventions the primary tumor with mesenteric lymph node metastases as well as the cystic liver metastasis could be resected. After surgical treatment an R1 situation at the mesenteric site and suspicious para-aortic lymph nodes remained. The long established treatment of factor-V Leiden mutation by anticoagulation with phenprocoumon was supplemented by deep subcutaneous injection of lanreotide autogel every 4 weeks. Currently, there is no evidence for progressive disease and the patient is without clinical signs of a carcinoid syndrome.

Contrast-enhanced ultrasound (CEUS) in hepatic lymphoma: retrospective evaluation in 38 cases.

PURPOSE: Description of contrast-enhanced ultrasound (CEUS) patterns of hepatic lymphoma. MATERIALS AND METHODS: Over a period of 6 years and 1 month from January 2006 to January 2012, n = 38 patients with histological or clinically apparent hepatic lymphoma were studied by means of CEUS prior to B-mode imaging. RESULTS: Using B-mode imaging, lesions were hypoechoic in n = 37 (97.4 %) cases, while a focal lymphoma lesion was echo-rich in 1 case (2.6 %). For comparison, with CEUS, a hyperenhanced signal during the arterial phase was observed in n = 9 (23.7 %), an isoenhanced signal in n = 17 (44.7 %) and a hypoenhanced signal in n = 12 (31.6 %) cases. During the portal phase n = 2 (5.3 %) lesions were isoenhanced and n = 36 (94.7 %) were hypoenhanced followed by a hypoenhancement in n = 38 (100 %) cases in the late phase. CONCLUSION: Lymphomas of the liver can cause different contrast accumulation in the arterial phase of CEUS. Furthermore, a clear differentiation from other malignant liver lesions such as metastases is crucial as different contrast accumulation in the arterial phase of CEUS is observed. In the late phase, hepatic lymphomas lead to a hypoenhancement in CEUS, also known as a "wash-out" phenomenon. In conclusion, CEUS is helpful to differentiate hepatic lesions by means of evaluating the malignancy or benignancy. In this regard, the application of CEUS can help to find the right diagnosis. A final discrimination between malignant liver lesions, such as liver lymphomas, metastasis or HCC, remains impossible.

Evaluation of biopsy methods in the diagnosis of submandibular space pathology.

The aim of this study was to evaluate the performance of fine needle aspiration cytology (FNAC), ultrasound-guided core needle biopsy (USCNB), punch biopsy, and surgical excision biopsy in neoplasms presenting within the submandibular space. A retrospective analysis of all patients with a pathological diagnosis of a submandibular space neoplasm within a 12-year period (February 1999 to June 2011) was performed. Biopsy results were compared to histopathological diagnosis obtained from surgical excision biopsy. Eighty-one specimens from 44 patients met the search criteria (15 FNAC, 24 USCNB, 7 punch biopsy, and 35 surgical excision biopsy). The final diagnosis was established by USCNB, punch biopsy, or surgical excision biopsy and not by FNAC alone. Surgical excision biopsy was performed as a primary diagnostic (n = 8), secondary diagnostic (n = 15), or as a post-diagnostic therapeutic procedure (n = 12). Non-diagnostic results were: FNAC 11/15, USCNB 2/24, and punch biopsy 1/7. Diagnostic results were: FNAC 2/15, USCNB 20/24, and punch biopsy 5/7. No complications were reported. Although punch biopsy demonstrated good yield and accuracy, its use is restricted to a small cohort of patients. USCNB is a safe and accurate technique in the submandibular space, with a low non-diagnostic rate.

Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP).

BACKGROUND: To investigate whether addition of cetuximab to standard adjuvant chemotherapy with gemcitabine improves outcome in pancreatic cancer, specifically whether the rate of disease-free survival (DFS) at 18 months (primary end point) exceeds the previously reported 35% of gemcitabine alone. PATIENTS AND METHODS: Prospective, open-label, multicenter, nonrandomized phase II study in 76 patients with R0- or R1-resected ductal adenocarcinoma of the pancreas included between October 2006 and November 2008. Gemcitabine and cetuximab were administered for 24 weeks. Secondary end points included overall survival (OS) and toxic effect. RESULTS: Seventy-three patients received cetuximab. Median DFS was 10.0 [95% confidence interval (CI) 8.9-13.6] months and the DFS rate at month 18 of 27.1% (16.7%-37.6%) was inferior to 35%. Median OS was 22.4 (18.2-27.9) months. Subgroup analyses revealed a nonsignificant increase in DFS for patients with versus without skin toxic effect ≥ grade 2 (median 14.7 versus 8.3 months, P = 0.073) and wild-type versus mutated K-Ras (median 11.5 versus 9.3 months, P = 0.57). Grade 3/4 toxic effects included neutropenia (11.0%), thrombopenia (7%), skin toxic effect (7%) and allergic reactions (7%). CONCLUSION: Addition of cetuximab to adjuvant gemcitabine does not seem to improve DFS or OS of unstratified pancreatic cancer patients. Trends for improved DFS in patients with wild-type K-Ras and skin toxic effect remain to be confirmed.

[A 79-year-old man with B symptoms and jaw claudication]. / B-Symptomatik und Kauclaudicatio bei einem 79-jährigen Patienten.

A 79-year-old patient presented with weight loss, subfebrile body temperature and unclear jaw pain. After ruling out malignant and infectious causes, positron emission tomography-computed tomography (PET-CT) revealed markedly elevated glucose utilization of the large thoracic and upper limb arteries, suggesting systemic vasculitis. Color-coded duplex sonography confirmed thickening of the wall of the external carotid artery consistent with vasculitis. The patient was diagnosed with giant cell arteritis involving the large thoracic arteries and the upper limb arteries but without involvement of the superficial temporal artery. Based on the involvement of the external carotid artery, the jaw pain could be classified as jaw claudication. Clinical and laboratory remission was achieved with systemic glucocorticoids which could subsequently be tapered. The patient is well and asymptomatic 12 months after diagnosis and 2 months without steroids.

New developments in pancreatic cancer treatment.

Pancreatic ductal adenocarcinomas belong to the most aggressive solid malignancies. The devastating prognosis of this tumor entity is associated with a high degree of resistance to systemic therapy approaches. Although new combination chemotherapy regimens have recently demonstrated a significant survival benefit compared to gemcitabine-based therapies, the search for novel treatment options still remains a huge challenge. After numerous potential targets have proven to be futile in clinical trials, recent efforts have been made to both improve drug delivery and to identify drugs targeting novel signalling pathways within the tumors including the putative stem cell compartment and the tumor stroma. Furthermore, predictive markers are needed to define tailored treatment regimens according to the molecular profile of individual tumors. In this review, current therapeutic strategies as well as emerging avenues for systemic therapy and response prediction for individualized therapy of pancreatic cancer patients are discussed which are currently evaluated to overcome the highly drug-resistant phenotype of this malignancy.