The role of intraoperative frozen section of central neck lymph nodes in the management of patients preoperatively diagnosed with low- risk differentiated cancer.

INTRODUCTION: Histological examination during surgery (FS) has a place in the surgical management of differentiated thyroid carcinoma (DTC). Extending the indication for limited surgery to 4 cm tumor size (ATA guidelines 2015) cytologically verified DTCs, increases the emphasis on accurate patient selection. In our work, we reflected on the effectiveness of FS and its relationship to optimal patient management. METHODS: In a single-center retrospective study, we evaluated the documentation of patients indicated for primary surgery for DTC from January 1, 2016 to December 31, 2020 - there was 489 patients collectively, 121 were men, median age was 50 years (1681), 73 patients (female, age 1845 years) with preoperatively identified low-risk DTC (size 1140mm) were indicated for lobectomy. RESULTS: 34 patients (46.6%) did not meet the criteria for limited surgery 15 patients were identified from FS of the lymph nodes of the central compartment (LNCK) (15 of 25 patients) - 1 patient with false negative result and 6 patients with FS of the thyroid gland (SH) (6 / 41) - 11 patients with false negative findings. Two-step OP surgery was performed on 13 patients (17.8%). FS of LNCK identified high-risk cancer and reduced the risk of two-step surgery compared to the group of patients in whom FS was not performed or was performed from thyroid gland. The difference was statistically significant (OR 1.93, p=0.026). CONCLUSION: Approximately ½ of the patients from preoperatively identified low-risk cancers in our cohort met the criteria for limited surgery. About 30% of them eventually needed a two-step operation. Perioperative examination of LNCK helps to perform radical surgery at one time.

Postoperative pancreatic fistula after pancreatic resection.

BACKGROUND: The failure of pancreatic anastomosis after the proximal pancreaticoduodenectomy (PD) and the failure of pancreatic stump after the distal pancreatectomy with a resulting postoperative pancreatic fistula remain the most feared complications after pancreatic resection. Surgeons have been trying to find a reliable reconstructive technique of pancreatic anastomosis for decades. METHODS: A literature search was performed to January 2020. Studies giving a detailed description of the pancreatic anastomosis after open PD and pancreatic stump closure techniques after the distal pancreatectomy were included. The aim of this study was review reported data derived from meta-analyses concerning the incidence of POPF according to the International Study Group of Pancreatic Surgery. A comparison of various surgical techniques and their impact on POPF incidence was made. RESULTS: In the group of clinically relevant POPF (CR- POPF), a well established difference between the patients undergoing POPF-associated interventional drainage or reoperation was observed. Meta-analyses showed that the patients with CR- POPF were statistically more likely to have a small duct size, soft gland texture, particular pancreatic neoplasms and an excessive intraoperative blood loss. CONCLUSION: Grade C POPF following PD, although uncommon, occurs with a defined incidence and is associated with a substantial morbidity, prolonged hospitalization, delayed recovery and a significant mortality. According to the results of various meta-analyses, pancreatogastrostomy and pancreatojejunostomy seemed to be comparable anastomotic techniques following PD (Ref. 54).

Ampullary cancer in a patient with familial adenomatous polyposis - a rare case report and current status of management.

Familial adenomatous polyposis (FAP) is an inherited autosomal dominant disorder. Extracolonic manifestations are seen quite often. As prophylactic colectomy has become a standard care in FAP patients, the concerns over the development of associated extracolonic malignancies have become more prevalent. The authors report a case of a patient with the history of subtotal colectomy because of FAP with the development of adenocarcinoma of papilla of Vater twenty-six years later. A radical procedure in form of proximal pancreaticoduodenectomy was indicated. Variable endoscopic surveillance protocols and treatment strategies have been proposed concerning the management of duodenal and periampullary lesions. In case of periampullary malignancies, the radical surgical resection offers the only chance for cure and the only option that may safeguard the long­term survival (Fig. 2, Ref. 30). Keywords: ampulla of Vater, bile duct, obstructive jaundice, pancreatoduodenectomy, periampullary tumors.

Recurrence after sentinel lymph node biopsy in cutaneous melanoma: a single-center experience in Slovak patients.

The standard approach in the management of cutaneous malignant melanoma is considered to be a complete excision of the primary lesion with an appropriate margin of the normal tissue according to Breslow thickness. Usually sentinel lymph node biopsy (SLNB) can help to determine the nodal status, and thus improve the accuracy of staging of the disease. However, the role of SLNB in melanoma treatment remains controversial. NCCN guidelines strongly support routine performance of therapeutic lymphadenectomy in all melanoma patients with clinically positive nodes without radiographic evidence of distant metastases. Patients with positive SLNB should have had completion lymph node dissection (CLND) for regional disease control. Between 2012 and 2016, 168 consecutive patients underwent surgery for primary cutaneous malignant melanoma at St. Elisabeth Cancer Institute in Bratislava. The indication for SLNB and the procedure was made according to international guidelines. In this retrospective study, a cohort of 78 patients was analyzed (35 women and 43 men). Inclusion criteria comprised patients with cutaneous melanoma with no evidence of distant metastases or clinical lymphadenopathy. SLNB comprised a dual labelling method (Tc-99m Nanocolloid / blue dye) in a one-day protocol. Median follow-up was 657 days. The primary composite outcome was the time to the first disease-related event (death, reintervention, worsening of symptoms). Primary outcome measures were overall (disease-specific) and disease-free survival. The overall identification rate of SLN in melanoma patients by dual labelling method was 98.5%. All patients with positive SLNB on frozen section underwent complete regional lymphadenectomy. Using multivariable analysis Breslow thickness of the lesion (p=0.00004, HR 4.03 on logarithmic scale) was identified as the strongest independent predictor of the disease-free survival (DFS) and male gender was significant predictor of DFS. An increase in tumor thickness was associated with significantly higher risk of an event. Neither SLN positivity nor initial S-100 level proved to be significant predictors of the event at the 0.05 level of probability. Multidisciplinary approach represents the gold standard of care for melanoma patients and surgery remains the best option for most localized cases. Although the usefulness of SLNB procedure has been questioned, it provides an excellent staging method, moreover, it can identify high-risk patients. The routine use of completion lymphadenectomy after a positive SLNB is still controversial. It is not clear whether CLND following a positive SLN biopsy improves survival but it could provide regional disease control.

[Total duodenopancreatectomy for renal cell carcinoma metastases - case report]. / Totálna duodenopankreatektómia pre metastázy renálneho karcinómu kazuistika.

INTRODUCTION: The frequency of pancreatic metastases ranges from 2% to 5%. Pancreas is an elective site for metastases from renal carcinoma. Pancreatic metastases from renal cell carcinoma are frequently the only metastatic site and they typically occur in the seventh decade of life. CASE REPORT: We report 1 female patient (aged 58 years) with multifocal and isolated pancreatic metastases of renal cell carcinoma. Total duodenopancreatectomy was performed. CONCLUSION: In selected cases, pancreatic resection due to renal cell cancer metastases is deemed indicated, improving overall patient survival. KEY WORDS: renal cell carcinoma (RCC) isolated pancreatic metastases total duodenopancreatectomy.

Surgical management of breast cancer liver metastases.

We analyzed the treatment results in patients who underwent hepatic resection for breast cancer liver metastases(BCLM).Between 1/2003 and 12/2012, 15 patients underwent hepatic resection for BCLM. All primary breast tumors were diagnosed as invasive breast cancer. Synchronous BCLM ocurred in 2 patients and 13 patients presented with metachronous BCLM. Median age of patients at the time of BCLM diagnosis was 51 years(range from 31 to 73 years). All resections were considered as R0. From among 15 resections we performed 10 major hepatic resections according to Couinaud classification(≥3 segments) and the rest were minor ones. There was no postoperative mortality within 60 days . All postoperative complications were managed conservatively. Median hospital stay was 10,5 days, ranging from 7-14 days.Standard therapy for patients with BCLM remains systemic chemo- and hormonal therapy. Hepatic resection as a part of multimodal treatment in tertiary HPB centers can offer in a selected group of patients a safe option for improved survival.

Surgical management of breast cancer liver metastases.

We analyzed the treatment results in patients who underwent hepatic resection for breast cancer liver metastases(BCLM).Between 1/2003 and 12/2012, 15 patients underwent hepatic resection for BCLM. All primary breast tumors were diagnosed as invasive breast cancer. Synchronous BCLM ocurred in 2 patients and 13 patients presented with metachronous BCLM. Median age of patients at the time of BCLM diagnosis was 51 years(range from 31 to 73 years). All resections were considered as R0. From among 15 resections we performed 10 major hepatic resections according to Couinaud classification(≥3 segments) and the rest were minor ones. There was no postoperative mortality within 60 days . All postoperative complications were managed conservatively. Median hospital stay was 10,5 days, ranging from 7-14 days.Standard therapy for patients with BCLM remains systemic chemo- and hormonal therapy. Hepatic resection as a part of multimodal treatment in tertiary HPB centers can offer in a selected group of patients a safe option for improved survival. Keywords: breast cancer, liver metastases, hepatic resection.

A first case of endoscopical removal of an eroded adjustable gastric band in Croatia.

Laparoscopic gastric banding (LAGB) is one of the most common surgical procedures in the treatment of morbid obesity since it provides good long-term outcomes in weight loss and decrease of comorbidities associated with obesity. Although the procedure has low morbidity and almost none-existing mortality, certain complications can occur. Erosion of the band into the gastric wall is one of the rare complications in LAGB. The reported incidence varies from 1 to 11%, however the largest study reported an incidence of 1.6%. This is in accordance with the incidence in our Centre for obesity, where only one case of erosion occurred among 112 operative procedures. The aim of this paper is to present a patient with gastric band erosion and it's removal by using the endoscopic techniques as a minimally invasive management method.

[Surgical treatment of metastases and its impact on prognosis in patients with metastatic colorectal carcinoma]. / Chirurgická liecba metastáz a jej vplyv na prognózu u pacientov s metastatickým kolorektálnym karcinómom.

BACKGROUND: Approximately one quarter of patients with colorectal carcinoma (CRC) have distant metastases at initial dia-gnosis and almost 50% will develop them during the disease course. Only radical surgical resection of metastases improves clinical outcome and offers a chance of longterm survival. Initially unresectable metastases can become resectable after downsizing with systemic therapy. MATERIALS AND METHODS: Retrospective analysis included 21 patients with metastatic colorectal carcinoma (mCRC) who were treated from 2006 to 2012 and underwent resection/ ablation of metastases. Fourteen patients had resection at initial dia-gnosis of metastatic disease and seven patients achieved operability of metastases after systemic treatment. The aim of the analysis was to evaluate surgical treatment of metastases and its impact on prognosis in patients with mCRC in correlation with clinical pathological  genetic factors. RESULTS: The median age of patients was 59 years. Fourteen patients had metastases in the liver, one patient had metastases in the lungs, two patients had combination of hepatic and extrahepatic metastases and four patients had metastases in other regions. During median followup of 47 months, 17 patients experienced disease progression and 13 patients died. Median progression free survival (PFS) after surgical resection/ ablation of metastases was 17 months (95% CI 13.8820.12), and median overall survival (OS) was 48 months (95% CI 38.7757.23). KRAS mutation was detected in 47.6% of patients and BRAF mutation in 9.5% of patients. Patients with BRAF mutation had worse PFS (median = 10 months vs 17 months; p = 0.523) and OS (median = 22 months vs 51 months; p = 0.05) compared to patients with BRAF wildtype. No difference was observed in PFS and OS between the patients with one or more metastatic lesions and between the patients who underwent resection/ ablation of metastases initially or after systemic treatment. CONCLUSION: These data suggest that resection/ ablation of metastases significantly improves prognosis of patients with mCRC and support the notion that mutated BRAF has a strong negative prognostic significance also in the group of patients, who undergo surgical resection/ ablation of metastatic lesions.

[Ductal carcinoma in situ (DCIS) and biopsy of the sentinel lymph node]. / DCIS a biopsia sentinelovej uzliny.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is the disease with increasing incidence. Nowadays, approximately 80% DCIS are diagnosed via mammography and represent more than 20% of all types of breast cancer. The acceptance of surgical procedures with this type of breast carcinoma is controversial as primary diagnosis of non-invasive carcinoma is often underestimated and in the end, histopathological examination reveals invasive carcinoma with biological potential to metastasize. In cases of "risk" patient groups with DCIS, several studies report lymph node metastases. The aim of the study has been to assess the incidence of sentinel lymph node metastatic involvement in high-risk patient group with DCIS and in ductal carcinoma in situ with microinvasion (DCISMI), to note the incidence of invasive carcinoma in definitive histopathology in patients with pre-operative diagnosis of DCIS and to analyze some predictors of invasivity. STUDY TYPE AND PATIENT GROUP: In retrospective analysis, we evaluated the setting of 119 patients who have been operated on at our Clinic from January, 1st 2008 until December, 31th 2010 for the diagnosis of DCIS. Prospectively, we have created the setting of 44 patients with high-risk DCIS with sentinel lymph node biopsy (SLNB) performed. METHODS AND RESULTS. Metastatic involvement of sentinel lymph node in high-risk DCIS has been found in 4 cases (9.0%)--in 1 patient (2.2%) with correct diagnosis of DCIS and in 3 patients (6.8%) with invasive carcinoma according to final histopathology. In the patient with DCIS, a micrometastasis of 0.4 mm was found in one sentinel lymph node. After complete axillary dissection, non-sentinel axillary lymph nodes metastatic involvement was not demonstrated (14/0). In 6 cases (5.0%), we identified DCISMI and did not find metastasis in sentinel lymph node. In the high-risk DCIS group, in 4 patients (9.0%) DCISMI and in 12 patients (27.2%) invasive carcinoma was found after definitive histopathologic examination. In this group, the overall ratio of invasive lesions was 36.2%. As for predictors of invasivity, high-grade carcinoma (OR 4.2; 95% CI 1,40-12,58) has more than 4-fold higher influence and lesion size

The interdisciplinary cooperation of forensic medicine, clinical medicine and palaeozoology: a case of cave bear (Ursus speloeus) bones.

Three pathologically modified bones (cranium, left mandible, iliac bone) of a cave bears (Ursus spelaeus) were found in the Last Glacial deposits (OIS 3) in the caves of the Vel'ká Fatra carst, Slovak republic. Despite of thorough paleontological examination, the bear bones were examined by experts in forensic medicine, traumatology and stomatology, too. The pathological changes were found in the tooth bed on the right side of the maxilla at the place of M1, being interpreted as a result of odontogenic purulent inflammation of soft tissues of tooth bed and surrounding bone. The iliac bone has an abnormally formed acetabulum with damaged and deformed osseous upper border, which could be a result of immoderate pressure of the head of femur, following with the mineral dysbalance (decalcification) or fracture of limbus acetobuli caused by injury. The mutual cooperation of all the abovementioned experts was declared as a very fruitful.

[Significance of the sentinel lymph node biopsy in early breast carcinomas]. / Význam biopsie sentinelovej uzliny pri vcasnom karcinóme prsníka.

We present our experience regarding sentinel lymph node biopsy (SLNB) at St. Elizabeth Institute of Oncology during 48 months. From January 1st, 2006 until December 31st, 2009, we had performed SLNB in 269 patients. Primary tumour size was 0.3-3.5cm including non-invasive breast carcinoma (i.e. TIS, T1 and T2 of TNM classification). Invasive carcinoma accounted for 255 (94.8%) cases, while non-invasive carcinoma for 14 (5.2%) cases. From total of 269 patients with invasive carcinoma, we used validation method in 157 (72.7%). In 255 patients with invasive carcinoma, sentinel node was not identified in 4 (1.6%) cases--in 1 patient with T1 invasive carcinoma and in 3 patients with T2 tumours. False negativity of sentinel node in T1 tumours was 4.3%. The incidence of macrometastases in sentinel nodes was confirmed using standard histopathologic examination with hematoxylin-eosin stain. In negative instances, the examination was then completed with serial sections and immunohistochemistry using cytoskeletal antibodies for confirmation of presence of micrometastases. In 6 (2.4%) cases, we found micrometastase in originally negative sentinel lymph node. Subsequent axillary dissection has not confirmed non-sentinel nodes involvement.

Enterovirulent E. coli in inflammatory and noninflammatory bowel diseases.

We determined the incidence of enterovirulent E. coli (EVEC; which can to cause gastrointestinal infections) in strains isolated from patients with both of the major inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) and from patients with noninflammatory bowel diseases (nonIBD). Cell detachment E. coli (CDEC) were detected in 14 % of all strains. A significant difference in the presence of CDEC was found between the groups of strains isolated from UC (24.1 %), nonIBD (11.9 %) and CD (4.7 %). Enteroaggregative E. coli (EAggEC) were detected in 2.5 %, typical enteropathogenic strains (EPEC) in 1.3 % and enterotoxigenic ones (ETEC) in 1.5 %. Enteroinvasive (EIEC) and shigatoxin producing E. coli (STEC) were not detected. Some strains showed a high invasion level in gentamicin-protection assay. These strains could therefore belong to adherent-invasive E. coli (AIEC) because they are free of genes encoding invasins (ipaH, ial) and are equipped with fimA gene. However, complete characterization of these strains and their classification as AIEC will require further tests.

[Central cervical dissection of lymph nodes in the management of differentiated thyroid carcinoma--our experience]. / Centrálna krcná disekcia lymfatických uzlín v liecbe diferencovaného karcinómu stítnej zl'azy--na e skúsenosti.

INTRODUCTION: Total thyroidectomy (TTE) with central compartment lymphonodes (LU) dissection remains a standard procedure in the treatment of differentiated thyroid carcinomas. METHODOLOGY: The retrospective study assessed a group of patients undergoing primary or secondary procedures in our clinic. PATIENT GROUP: From 01.01. 2005 to 31. 07. 2007, a total of 50 patients underwent primary procedures, TTE with dissection of central compartment lymphonodes was performed in 18 patients, 58 patients were reoperated for relapses of the disorder. In the primary procedures, the central compartment lymphonodes were affected with increased rate, proportionally to a T-stage of the disorder 28% (T1), 52 (T2), 58% (T3). Multifocal carcinoma was associated with a high risk, where metastatic lymphadenopathy occured in 53% of the cases. In the reoperated subjects, relapses of the disorder were recorded in 78% of the patients in their central compartment lymphonodes and their thyreoglobulin levels decreased. Out of 126 patients, paresis of the nervus laryngeus reccurens was recorded in 4 subjects (3.1%) and postoperative hypoparathyreosis in 14 subjects (11%). CONCLUSION: Dissection of lymphonodes is a standard part of the surgical management of differentiated carcinomas, providing local control of the disease. 78% of the relapses were located within the central compartment. Risk and complication rates correspond to those reported in total thyroidectomy.

Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat.

OBJECTIVE: The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). METHODS: Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. RESULTS: Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. CONCLUSIONS: NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.

[Completion of total thyroidectomy for a differentiated thyroid carcinoma]. / Dokoncenie totálnej tyreoidektómie pre diferencovaný karcinóm stítnej zl'azy.

Total thyroidectomy with dissection of the central compartment (CK) lymphatic nodes is a standard surgical procedure in differentiated thyroid carcinomas. A minority of the patients are diagnosed postoperatively. Our study reports on surgical tactics in these patients. During 2003-2006, 47 patients were operated, to have total thyoidectomy performed. The patients' data were assessed retrospectively.

Detection of Shiga toxins, intimin and enterohemolysin in Escherichia coli strains isolated from children in eastern Slovakia.

Fifty Escherichia coli strains isolated from stool samples of 51 healthy children, 143 strains isolated from stool samples of 327 children with diarrhea and 24 strains isolated from stool samples of 21 children with suspected hemolytic uremic syndrome were examined for the presence of Shiga toxin-producing E. coli virulence factors (shiga toxin 1 and 2, intimin and enterohemolysin) and their genes. Vero-cell assay and latex agglutination were used for detection of Shiga toxin 1 and 2, TSB agar with washed erythrocytes was used for detection of enterohemolysin; genes encoding shiga toxin 1 and 2, intimin and enterohemolysin were detected using multiplex PCR. The presence of E. coli strains harboring genes encoding shiga toxin 1 and 2 (12 strains), intimin (34 strains) and enterohemolysin (12 strains) was demonstrated.

Glucocorticoids decrease c-fos expression in human nasal polyps in vivo.

BACKGROUND: Activated c-fos binds to jun proteins to form the activation protein 1 (AP-1) transcription factor that regulates cytokine and other proinflammatory genes. c-Fos may play a key role in nasal polyp formation. Glucocorticoids may exert their anti-inflammatory effects through an interaction of glucocorticoid receptors with AP-1 that leads to mutual inactivation of both factors, and a "default" termination of AP-1 mediated gene activation. This may explain the beneficial effects of glucocorticoids in the treatment of nasal polyps. METHODS: To test this hypothesis in humans in vivo the immunohistochemical expression of c-fos-immunoreactive material (c-fos-irm) was assessed in nasal polyps from eight steroid naive subjects, polyps from eight subjects treated with topical beclomethasone dipropionate (BDP), and normal inferior turbinate nasal mucosa (n = 6). RESULTS: mRNA for c-fos was detected in all nasal polyps and normal mucosa. In contrast, c-fos-irm was present in all steroid naive subjects but in only two of the eight subjects treated with BDP (p = 0.007, two-tailed Fisher's exact test). c-Fos-irm was expressed solely in epithelial cells and glandular structures; it was expressed in normal epithelium and glands, but the staining intensity was low. CONCLUSION: Glucocorticoids appear to modulate expression of c-fos-irm and possibly AP-1 in human airway epithelial cells in vivo.

Mucoglycoprotein hypersecretion in allergic rhinitis and cystic fibrosis.

There is little information about specific changes in submucosal gland exocytosis in diseases such as allergic rhinitis (AR), nonallergic rhinitis (NAR), and cystic fibrosis (CF). Nasal lavage fluids were collected from normal, AR, NAR, and CF subjects. Concentrations of lysozyme, Alcian blue-staining mucoglycoconjugate material (AB + m), and human high-molecular-weight mucoglycoconjugates recognized by the 7F10 murine monoclonal antibody [7F10-immunoreactive mucoglycoconjugates (7F10-irm)] were measured. AB + m and 7F10-irm were characterized by Sepharose-2B column chromatography and glycosidase digestion. 7F10-irm was increased in CF (2.4-fold; P = 0.001) and AR (12.7-fold; P = 0.00007) subjects. AB + m was increased in CF (1.8-fold; P = 0.049) and AR (1.2-fold; P = 0.07) subjects. There were no changes in NAR subjects. On Sepharose-2B columns, AB + m peaks were at 1.3-3.0 x 10(6) and 0.36-0.65 x 10(6) Da. 7F10-irm showed four distinct peaks at 1.5, 1.2, 0.85, and 0.53 x 10(6) Da that were nearly identical in both normal and CF samples. Sialic acid was present in both 7F10-irm and AB + m. 7F10-irm and AB + m are mutually exclusive sialylated mucoglycoproteins that are significantly induced in AR and CF but not in NAR.

Hyaluronan is exocytosed from serous, but not mucous cells, of human nasal and tracheobronchial submucosal glands.

BACKGROUND: Hyaluronan is a large, nonsulfated glycosaminoglycan that is a major component of many extracellular matrices. Secretion of hyaluronan has been associated with inflammation in the lungs and other tissues. The purpose of the present study was to determine the distribution of hyaluronan in human respiratory tissues and to determine if hyaluronan was present in human nasal secretions. METHOD: Hyaluronan was localized in histological sections of human nasal and tracheobronchial mucosa using a biotinlabeled affinity-purified hyaluronan binding probe derived from cartilage proteoglycan (b-PG) (Green et al. Exp Cell Res 1988; 178:224-32). Subjects had saline nasal provocation to collect baseline nasal secretions, then ate chili peppers to provoke parasympathetic cholinergic nasal glandular secretion (gustatory provocation). Total protein and hyaluronan concentrations were measured in the lavage fluids. RESULTS: Staining for hyaluronan was intense in basement membranes of epithelium, glands and vessels, and perivascular adventitia. Many epithelial cells contained hyaluronan, but the staining intensity was less than that on the basolateral aspects of these cells. Submucosal gland serous cells contained variable amounts of hyaluronan. Hyaluronan was not present in goblet cells, submucosal gland mucous cells, or sub-basement membrane collagen deposits. The gustatory, parasympathetic stimulus induced a 4-fold increase in hyaluronan secretion (P < 0.01) and a 3.5-fold increase in total protein release (P < 0.0010). Hyaluronan accounted for 75% to 80% of the polymeric uronic acids in human nasal secretions. CONCLUSION: Hyaluronan was present human respiratory epithelial cells and submucosal gland serous cells and was exocytosed in response to parasympathetic stimulation. This distribution suggests roles in packaging cationic proteins in serous cells, cellular adhesion to basement membranes, and activation of macrophages in airway lumens.