Recurrent Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1 Syndrome.

Primary hyperparathyroidism is a common endocrinopathy. Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare autosomal dominantly inherited endocrine tumor predisposition syndrome, with one of main manifestations being primary hyperparathyroidism. We retrospectively evaluated a set of 1011 patients who underwent surgery for primary hyperparathyroidism between the years 2018-2022, and found 78 (8 %) patients who underwent reoperations and 27 patients with MEN1 syndrome. In the group of patients with MEN1 syndrome, 7 (35 %) needed reoperations. Patients with multiple endocrine neoplasia syndrome have a higher risk of needing reoperation. Genetic testing can help identify MEN1 syndrome preoperatively and to better evaluate the approach to surgery.

Concomitant thyroid disease in patients operated for primary hyperparathyroidism.

INTRODUCTION: Parathyroid and thyroid diseases are ones of the most common endocrine diseases, but simultaneous surgical treatment of both endocrine systems is still under discussion. METHODS: We retrospectively evaluated 1,574 patients operated for primary hyperparathyroidism at the 3rd Department of Surgery, 1st Faculty Medicine, Charles University and University Hospital Motol in Prague with the thyroid and parathyroid ultrasound reports available. The patients were divided into two groups - with and without thyroid surgery. RESULTS: Thyroid surgery was performed in 34% of patients with primary hyperparathyroidism. Group 2, where thyroid surgery was performed, showed a higher proportion of reported abnormal thyroid sonographic findings (74%), a higher proportion of bilateral throat exploration (69%) and a longer hospital stay (3.3 days). CONCLUSION: A patient indicated for surgery for parathyroid disease should also be indicated for possible thyroid surgery.

Measurement of intact parathormone during operation for primary hyperparathyroidism.

In this prospective study, the role of the intact parathormone (iPHT) levels for the verification of pathologic parathyroid tissue removal during parathyroidectomy, was analyzed in 441 patients diagnosed with primary hyperparathyroidism. The level of intact parathormone was obtained before the initial incision (baseline level) and 10 minutes after the pathologic parathyroid gland removal (control value). In 80 % of cases, the decrease of intact parathormone was more than 50 % of the baseline level. The comparison of preoperative and postoperative intact parathormone levels can also be used as marker of parathyroid hyperplasia or persistent hyperparathyroidism. This method is necessary mainly for performance of focused, miniinvasive approaches as well as in reoperations. This method is of significant benefit in cases of negative preoperative examination methods. The determination of intact parathormone level increases the success of parathyroidectomy (Ref. 26).

[Videothoracoscopic excision of mediastinal parathyroid adenoma in primary hyperparathyroidism]. / Videothorakoskopické odstranení mediastinálne ulozeného adenomu prístítného telíska pri primární hyperparathyreóze.

INTRODUCTION: Primary hyperparathyroidism is a disease caused by elevated secretion of parathyroid hormone from pathological parathyroid glands. After the diagnosis, the success of its surgical solution depends predominantly on surgical management and experience of the surgeons. A special group is formed by ectopic localizations of pathologically enlarged parathyroid glands in the mediastinum, which require a modified surgical approach. When the adenoma is deep in the mediastinum, sternotomy or thoracotomy is indicated; alternatively, a minimally invasive approach can be used - videothoracoscopic thymectomy. CASE REPORT: We present a case of a patient with normocalcemic recurrent primary hyperparathyroidism. This patient underwent a minimally invasive video-assisted thymectomy after scintigraphic confirmation of parathyroid adenoma in the mediastinum. CONCLUSION: The removal of parathyroid adenoma in the mediastinum using the videothoracoscopic method is safe. Compared to sternotomy, this method improves the postoperative period, reduces the length of stay and provides more comfort to patients. We recommend considering the videothoracoscopic method in cases where the pathologically enlarged parathyroid gland is localized in the inferior and anterior mediastinum. KEY WORDS: primary hyperparathyroidism adenoma of glandula parathyroidea - mediastinum miniinvasive.

Transcriptional repression of IFNß1 by ATF2 confers melanoma resistance to therapy.

The resistance of melanoma to current treatment modalities represents a major obstacle for durable therapeutic response, and thus the elucidation of mechanisms of resistance is urgently needed. The crucial functions of activating transcription factor-2 (ATF2) in the development and therapeutic resistance of melanoma have been previously reported, although the precise underlying mechanisms remain unclear. Here, we report a protein kinase C-ɛ (PKCɛ)- and ATF2-mediated mechanism that facilitates resistance by transcriptionally repressing the expression of interferon-ß1 (IFNß1) and downstream type-I IFN signaling that is otherwise induced upon exposure to chemotherapy. Treatment of early-stage melanomas expressing low levels of PKCɛ with chemotherapies relieves ATF2-mediated transcriptional repression of IFNß1, resulting in impaired S-phase progression, a senescence-like phenotype and increased cell death. This response is lost in late-stage metastatic melanomas expressing high levels of PKCɛ. Notably, nuclear ATF2 and low expression of IFNß1 in melanoma tumor samples correlates with poor patient responsiveness to biochemotherapy or neoadjuvant IFN-α2a. Conversely, cytosolic ATF2 and induction of IFNß1 coincides with therapeutic responsiveness. Collectively, we identify an IFNß1-dependent, cell-autonomous mechanism that contributes to the therapeutic resistance of melanoma via the PKCɛ-ATF2 regulatory axis.

Stem cells regenerative properties on new rat spinal fusion model.

Stem cells biology is one of the most frequent topic of physiological research of today. Spinal fusion represents common bone biology challenge. It is the indicator of osteoinduction and new bone formation on ectopic model. The purpose of this study was to establish a simple model of spinal fusion based on a rat model including verification of the possible use of titanium microplates with hydroxyapatite scaffold combined with human bone marrow-derived mesenchymal stem cells (MSCs). Spinous processes of two adjacent vertebrae were fixed in 15 Wistar rats. The space between bony vertebral arches and spinous processes was either filled with augmentation material only and covered with a resorbable collagen membrane (Group 1), or filled with augmentation material loaded with 5 × 106 MSCs and covered with a resorbable collagen membrane (Group 2). The rats were sacrificed 8 weeks after the surgery. Histology, histomorphometry and micro-CT were performed. The new model of interspinous fusion was safe, easy, inexpensive, with zero mortality. We did not detect any substantial pathological changes or tumor formation after graft implantation. We observed a nonsignificant effect on the formation of new bone tissue between Group 1 and Group 2. In the group with MSCs (Group 2) we described minor inflamatory response which indicates the imunomodulational and antiinflamatory role of MSCs. In conclusion, this new model proved to be easy to use in small animals like rats.

Postoperative rectal anastomotic complications.

Colorectal cancer represents the most common tumour of the gastrointestinal tract and the second most common tumour in men as well as women. The trend of increasing incidence of colorectal cancer is alerting. We undertook a retrospective study on 588 patients with rectal cancer and operated by rectal resection with anastomosis between the years 2002-2012. In our sample, we observed 54 (9.2 %) cases of anastomosis insufficiencies requiring reoperation. Out of 54 insufficient anastomoses, 36 (66 %) were in the lower two thirds of the rectum and only 18 (34 %) in the oral one. Although we have observed similar occurrences of anastomosis insufficiency in both groups - classical vs. staple suture (9.5 % and 9.0 %, respectively), the majority of stapler anastomoses (94 %) were made in the aboral part of the rectum. However, we can state that a majority of authors prefer the staple anastomosis as the one with lowest risk, mainly in the distal region of anastomosis. The high ligation of inferior mesenteric artery was performed in 182 (31 %) patients; out of these, we observed anastomosis insufficiency in 12 cases (22 %), which is exactly similar to that in the group of patients without high ligation of the inferior mesenteric artery. We did not observe the use of antibiotics in therapeutical doses as a positive factor for anastomosis insufficiencies, and neither was oncological therapy observed as a risk factor. In our group of patients we agreed that age, level of anastomosis and corticosteroids are high-risk factors. The purpose of these reports, is for the sake of future to share and reference our experiences with cases of rectal and rectosigmoideal resection over the last 11 years. We consider it important to reference our results, especially the risk factors regarding the healing of rectal anastomosis, because anastomotic healing is a surgical problem with potentially deadly consequences for patients (Tab. 4, Ref. 24).

Arthroscopic lysis and lavage in patients with temporomandibular anterior disc displacement without reduction.

The authors prospectively analysed 50 patients with chronic anterior disc displacement without reduction, who underwent arthroscopic lysis and lavage of the temporomandibular joint (TMJ). Patients with symptoms lasting less than 1 year were assigned to Group A (n=28) and patients with symptoms lasting more than 1 year to Group B (n=22). The most common problems were inflammatory changes of synovial and retrodiscal tissue (Group A, 71%; Group B, 82%). Fibrous adhesions were present in 14% of Group A patients and 45% of Group B patients. Degenerative changes of the disc and articular surface were present in 4% of Group A patients and 32% of Group B patients. Mouth opening increased 123% from baseline in Group A, and 112% in Group B (P<0.05). Pain decreased significantly in both groups (Group A, 2.5 points; Group B, 1.68 points; P<0.05). In conclusion, almost all patients with chronic anterior disc displacement without reduction benefited from arthroscopic lysis and lavage of the TMJ. Patients with a shorter duration of symptoms problems benefited more than those with a longer duration. Arthroscopic lysis and lavage of the TMJ is safe and beneficial in chronic anterior disc displacement without reduction.

Neurogenic pulmonary edema induced by spinal cord injury in spontaneously hypertensive and Dahl salt hypertensive rats.

Neurogenic pulmonary edema (NPE), which is induced by acute spinal cord compression (SCC) under the mild (1.5 %) isoflurane anesthesia, is highly dependent on baroreflex-mediated bradycardia because a deeper (3 %) isoflurane anesthesia or atropine pretreatment completely abolished bradycardia occurrence and NPE development in rats subjected to SCC. The aim of the present study was to evaluate whether hypertension-associated impairment of baroreflex sensitivity might exert some protection against NPE development in hypertensive animals. We therefore studied SCC-induced NPE development in two forms of experimental hypertension - spontaneously hypertensive rats (SHR) and salt hypertensive Dahl rats, which were reported to have reduced baroreflex sensitivity. SCC elicited NPE in both hypertensive models irrespective of their baroreflex sensitivity. It is evident that a moderate impairment of baroreflex sensitivity, which was demonstrated in salt hypertensive Dahl rats, does not exert sufficient protective effects against NPE development.

Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain.

The role of intraoperative positioning of the inferior alveolar nerve on postoperative paresthesia after bilateral sagittal split osteotomy of the mandible: prospective clinical study.

Bilateral sagittal split osteotomy (BSSO) aims to correct congenital or acquired mandibular abnormities. Temporary or permanent neurosensory disturbance is the most frequent complication of BSSO. To evaluate the influence of IAN handling during osteotomy, the authors undertook a prospective study in 290 patients who underwent BSSO. The occurrence and duration of paresthesia was evaluated 4 weeks, 3 months, 6 months, and 1 year after surgery. Paresthesia developed immediately after surgery in almost half of the patients. Most cases of paresthesia resolved within 1 year after surgery. A significantly higher prevalence of paresthesia was observed on the left side. The authors found a correlation between the type of IAN position between the left and right side. The type of split (and IAN exposure) did not have a significant effect on the occurrence or duration of neurosensory disturbance of the IAN. The authors did not find a correlation between the occurrence and duration of paresthesia and the direction of BSSO. Mandibular hypoplasia or mandibular progenia did not represent a predisposition for the development of paresthesia. In the development of IAN paresthesia, the type of IAN exposure and the split is less important than the side on which the split is carried out.

Piezosurgery in oral and maxillofacial surgery.

This review summarizes current knowledge and experience with piezosurgery, a promising, meticulous and soft tissue-sparing system for bone cutting, based on ultrasonic microvibrations. The main advantages of piezosurgery include soft tissue protection, optimal visibility in the surgical field, decreased blood loss, less vibration and noise, increased comfort for the patient and protection of tooth structure. To date it has been indicationed for use in oral and maxillofacial surgery, otorhinolaryngology, neurosurgery, ophthalmology, traumatology and orthopaedics. The main indications in oral surgery are sinus lift, bone graft harvesting, osteogenic distraction, ridge expansion, endodontic surgery, periodontal surgery, inferior alveolar nerve decompression, cyst removal, dental extraction and impacted tooth removal. In conclusion, piezosurgery is a promising technical modality for different aspects of bone surgery with a rapidly increasing number of indications throughout the whole field of surgery.

Hemimandibulectomy and therapeutic neck dissection with radiotherapy in the treatment of oral squamous cell carcinoma involving mandible: a critical review of treatment protocol in the years 1994-2004.

This retrospective non-randomized 10-year follow-up study compared 147 patients with squamous cell carcinoma (SCC) of the oral cavity requiring hemimandibulectomy, treated by surgical resection, therapeutic neck dissection and radiotherapy. The 5-year survival rates were compared related to localization, size of the tumour, infiltration of locoregional lymph nodes, distant metastases, histopathological grading, radicality of surgery, and invasion of tumour into the mandible. Occurrence of tumour relapse and its localization was studied. The mean 5-year survival rate was 26%. Patients with SCC of the mandibular alveolar process had higher rates; the lowest rates occurred in SCC of the buccal mucosa. Survival rate was significantly lower with insufficient resection of the tumour (85% relapse). An important number of patients with radical resection died within 3 months of surgery. In almost 55% of the mandibles tumour was not present. In 5% of infiltrated mandibles, dissemination into inferior alveolar nerve was proven. Decreasing survival rate was seen with increasing size of tumour and higher histological grade. Therapeutic neck dissection significantly reduces survival rate and increases the percentage of lymph node relapse. Elective neck dissection should be performed in SCC requiring hemimandibulectomy. Primary reconstruction should reverse the high percentage of postoperative complication arising from increased radicality.

The impact of Le Fort I advancement and bilateral sagittal split osteotomy setback on ventilation during sleep.

The impact of orthognathic surgery for class III malocclusion on ventilation during sleep was examined using a comparison of pre- and post-surgical respiratory parameters. 21 patients with both maxillary hypoplasia and mandibular excess underwent Le Fort I osteotomy and advancement together with bilateral sagittal split osteotomy (BSSO) setback. Respiratory parameters, ECG and position of the body were monitored before surgery and postoperatively after the fixation removal (mean 8.5 months). Average Le Fort I advancement was 4.44 mm, BSSO setback was 4.96 mm. Generally, the orthognathic procedure worsened breathing function during sleep, as reflected in significant increase of index of flow limitations and decrease in oxygen saturation. The posterior airways space decreased to 75% of its original volume, the distance between mandibular plane and hyoid bone increased to 133%. The results indicate that bimaxillary surgery for class III malocclusion increased upper airway resistance. A young person would probably be able to balance such a decline in respiratory function using different adaptive mechanisms, but the potential impact of orthognathic surgery on the upper airways should be incorporated in a treatment plan.

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair.

Macroporous hydrogels are artificial biomaterials commonly used in tissue engineering, including central nervous system (CNS) repair. Their physical properties may be modified to improve their adhesion properties and promote tissue regeneration. We implanted four types of hydrogels based on 2-hydroxyethyl methacrylate (HEMA) with different surface charges inside a spinal cord hemisection cavity at the Th8 level in rats. The spinal cords were processed 1 and 6 months after implantation and histologically evaluated. Connective tissue deposition was most abundant in the hydrogels with positively-charged functional groups. Axonal regeneration was promoted in hydrogels carrying charged functional groups; hydrogels with positively charged functional groups showed increased axonal ingrowth into the central parts of the implant. Few astrocytes grew into the hydrogels. Our study shows that HEMA-based hydrogels carrying charged functional groups improve axonal ingrowth inside the implants compared to implants without any charge. Further, positively charged functional groups promote connective tissue infiltration and extended axonal regeneration inside a hydrogel bridge.

Rapid but not slow spinal cord compression elicits neurogenic pulmonary edema in the rat.

The development of neurogenic pulmonary edema (NPE) can be elicited by an immediate epidural balloon compression of the thoracic spinal cord. To evaluate whether a slower balloon inflation could prevent NPE development, we examined the extent of NPE in animals lesioned with a rapid (5 microl - 5 microl - 5 microl) or slow rate (3 microl - 2 microl - 2 microl - 2 microl - 2 microl - 2 microl - 2 microl) of balloon inflation. These groups were compared with the NPE model (immediate inflation to 15 microl) and with healthy controls. Slow balloon inflation prevented NPE development, whereas the pulmonary index and histology revealed a massive pulmonary edema in the group with a rapid rate of balloon inflation. Pulmonary edema was preceded by a considerable decrease in heart rate during the inflation procedure. Moreover, rapid inflation of balloon in spinal channel to either 5 microl or 10 microl did not cause NPE. Thus, a slow rate of balloon inflation in the thoracic epidural space prevents the development of neurogenic pulmonary edema, most likely due to the better adaptation of the organism to acute circulatory changes (rapid elevation of systemic blood pressure accompanied by profound heart rate reduction) during the longer balloon inflation period. It should be noted that spinal cord transection at the same level did not cause neurogenic pulmonary edema.