Cross-Talk Between Nitrosative Stress, Inflammation and Hypoxia-Inducible Factor in Patients with Adrenal Masses.

BACKGROUND: Adrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma). METHODS: The plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05). RESULTS: We found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO- and IL-1ß depended on cortisol level, while ONOO-, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing's or Conn's adenoma. CONCLUSION: Adrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.

Training in intraoperative neuromonitoring of recurrent laryngeal nerves reduces the risk of their injury during thyroid surgery.

INTRODUCTION: Even though incidence of recurrent laryngeal nerve palsy (RLNP) is low, it affects importantly the quality of life of patients and remains one of main medicolegal litigation problems in surgery. Intraoperative neuromonitoring (IONM) has become widely accepted tool helping in recurrent laryngeal nerve identification, however no clear association of IONM with RLNP rate has been demonstrated. The aim of our study was to assess whether training in IONM influences rates of RNLP after thyroid surgery as an independent factor. MATERIAL AND METHODS: We analysed retrospectively 1235 patients who underwent thyroidectomy at the 1st Department of General and Endocrine Surgery, Medical University of Bialystok. Possible risk factors for RLNP were evaluated: application or not of IONM, the extent of surgery or thyroid pathology in correlation with surgeons' experience in IONM (trained or untrained). RESULTS: There were 2351 nerves at risk (NAR) and 39 RNLP were diagnosed after thyroid surgery (1.66%). Surgeons trained in IONM performed 52.2% of all operations (1200 NAR) with 7 RLNP (0.58%), whereas not-trained had 32 RLNP for 1151 NAR (2.8%; p < 0.001). After 182 thyroidectomies (357 NAR) guided by IONM (14.7%) 3 RLNP were observed (0.84%) vs. 36 palsies per 1994 NAR without IONM (1.81%; p = 0.189). The highest danger of RLNP was reported after reoperations and the lowest after subtotal thyroidectomies. We found no association between thyroid pathology and RLNP rate. CONCLUSIONS: According to our study training in IONM decreases chances of RLNP especially during total or near total thyroidectomy.

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients.

This study is the first to assess redox balance, glutathione metabolism, and oxidative damage to RNA/DNA, proteins, and lipids in the plasma/serum and urine of patients with adrenal masses. The study included 70 patients with adrenal tumors divided into three subgroups: incidentaloma (n = 30), pheochromocytoma (n = 20), and Cushing's/Conn's adenoma (n = 20), as well as 60 healthy controls. Blood and urine samples were collected before elective endoscopic adrenalectomy. Antioxidant defense capacity was significantly decreased (serum/plasma: superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), uric acid (UA); urine: SOD, GSH, UA) in patients with adrenal masses. The oxidative damage to proteins (advanced glycation end products (AGE), advanced oxidation protein products (AOPP)) and lipids (lipid hydroperoxides (LOOH), and malondialdehyde (MDA)) was higher in the plasma and urine of these patients. Plasma MDA and DNA/RNA oxidation products, with high sensitivity and specificity, can help to diagnose pheochromocytoma. This biomarker differentiates patients with pheochromocytoma from Cushing's/Conn's adenoma as well as from heathy controls. Plasma RNA/DNA oxidation was also positively correlated with urine metanephrine. Oxidative stress can play a crucial role in adrenal tumors. However, further studies are required to clarify the role of redox signaling in adrenal masses.

Bariatric Surgery Normalizes Protein Glycoxidation and Nitrosative Stress in Morbidly Obese Patients.

The results of recent studies indicate the key role of nitrosative stress and protein oxidative damage in the development of morbid obesity. Nevertheless, the effect of bariatric surgery on protein oxidation/glycation and nitrosative/nitrative stress is not yet known. This is the first study evaluating protein glycoxidation and protein nitrosative damage in morbidly obese patients before and after (one, three, six and twelve months) laparoscopic sleeve gastrectomy. The study included 50 women with morbid obesity as well as 50 age- and gender-matched healthy controls. We demonstrated significant increases in serum myeloperoxidase, plasma glycooxidative products (dityrosine, kynurenine, N-formyl-kynurenine, amyloid, Amadori products, glycophore), protein oxidative damage (ischemia modified albumin) and nitrosative/nitrative stress (nitric oxide, peroxy-nitrite, S-nitrosothiols and nitro-tyrosine) in morbidly obese subjects as compared to lean controls, whereas plasma tryptophan and total thiols were statistically decreased. Bariatric surgery generally reduces the abnormalities in the glycoxidation of proteins and nitrosative/nitrative stress. Noteworthily, in the patients with metabolic syndrome (MS+), we showed no differences in most redox biomarkers, as compared to morbidly obese patients without MS (MS-). However, two markers: were able to differentiate MS+ and MS- with high specificity and sensitivity: peroxy-nitrite (>70%) and S-nitrosothiols (>60%). Further studies are required to confirm the diagnostic usefulness of such biomarkers.

The Impact of Hypertension and Metabolic Syndrome on Nitrosative Stress and Glutathione Metabolism in Patients with Morbid Obesity.

In this pathbreaking study, we evaluated nitrosative stress in morbidly obese patients with and without metabolic syndrome. 62 women with class 3 obesity (BMI > 40 kg/m2) were divided into three subgroups: obese patients (OB), obese patients with hypertension (OB+HYP), and obese patients with metabolic syndrome (OB+MS). In comparison to the lean patients, OB had increased levels of serum myeloperoxidase (MPO), plasma nitric oxide (NO), S-nitrosothiols, and peroxynitrite (ONOO-), as well as nitrotyrosine, while oxidized glutathione (GSSG) rose only in OB+HYP group. Interestingly, ONOO- was significantly higher in OB+HYP and OB+MS as compared to OB group, while MPO only in OB+MS group. OB+MS had greater nitrotyrosine and S-nitrosothiol values than OB+HYP. Moreover, peroxynitrite could differentiate OB from OB+HYP and OB+MS (AUC 0.9292; p < 0.0001; 87.5% sensitivity, 90% specificity) as well as between OB and OB+MS group (AUC 0.9125; p < 0.0001; 81.25% sensitivity, 83.33%). In conclusion, we showed that MPO activity, NO formation, and nitrosative damage to proteins parallel the progression of metabolic disturbances of obesity. Evaluation of ONOO- concentrations may help predict the development of hypertension and metabolic syndrome in patients with morbid obesity; however, longer-term studies are required for larger numbers of patients.

Impact of Weight Loss on the Total Antioxidant/Oxidant Potential in Patients with Morbid Obesity-A Longitudinal Study.

The assessment of total antioxidant activity seems to have a higher diagnostic value than the evaluation of individual antioxidants separately. Therefore, this is the first study to assess the total antioxidant/oxidant status in morbidly obese patients undergoing bariatric surgery. The study involved 60 patients with Class 3 obesity (BMI > 40 kg/m2) divided into two equal subgroups: morbidly obese patients without and with metabolic syndrome. The analyses were performed in plasma samples collected before surgery as well as 1, 3, 6, and 12 months after a laparoscopic sleeve gastrectomy. Total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP), DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical assay, and total oxidant status (TOS) were significantly higher before surgery (as compared to the healthy controls, n = 60) and generally decreased after bariatric treatment. Interestingly, all assessed biomarkers correlated positively with uric acid content. However, the total antioxidant/oxidant potential did not differ between obese patients without metabolic syndrome and those with both obesity and metabolic syndrome. Only DPPH differentiated the two subgroups (p < 0.0001; AUC 0.8) with 73% sensitivity and 77% specificity. Plasma TAC correlated positively with body mass index, waist-hip ratio, serum insulin, and uric acid. Therefore, TAC seems to be the best biomarker to assess the antioxidant status of obese patients.

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

This is the first study to evaluate both the antioxidant barrier, glutathione metabolism, and oxidative damage to proteins and lipids in morbidly obese patients undergoing bariatric treatment. The study included 65 patients with class 3 obesity divided into two subgroups: morbidly obese patients without metabolic syndrome (OB) and obese patients with metabolic syndrome (OB + MS). Blood samples were collected before surgery as well as one, three, six, and twelve months after the bariatric treatment. Superoxide dismutase and reduced glutathione (GSH) were significantly decreased, whereas glutathione reductase and uric acid were enhanced in morbidly obese patients before bariatric surgery as compared to lean control. Moreover, in the OB group, we observed the increase of superoxide dismutase (SOD) and the decrease of uric acid (UA) after the bariatric treatment; however, these changes were not observed in the OB + MS group. The oxidative damage to proteins (advanced glycation end products, AGE; advanced oxidation protein products, AOPP) and lipids (8-isoprostanes, 8-isop; 4-hydroxynoneal) was higher in OB as well as OB + MS patients. We noticed that AGE and AOPP levels diminished after the bariatric treatment, whereas redox status (ratio of GSH to oxidized glutathione) was still reduced in the OB + MS group. Summarizing, morbid obesity is associated with disturbances in the antioxidant barrier and enhanced oxidative damage to proteins and lipids. Although bariatric surgery improves redox homeostasis in obese patients, those with metabolic syndrome show a continuous decrease in the antioxidant status. In patients undergoing bariatric treatment, antioxidant supplementation may be considered.

The impact of laparoscopic adrenalectomy on renal function. Results of a prospective randomised clinical trial.

INTRODUCTION: Laparoscopic adrenalectomy is the gold standard management of benign adrenal masses and isolated metastases to adrenal glands. Two techniques of endoscopic adrenalectomy: lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) seem to be equally safe and effective. Recent studies suggest advantages of PRA over LTA in terms of lower intensity of postoperative pain, shorter hospital stay, faster recovery, and lower early morbidity. However, PRA involves high insufflation pressure of CO2 within a limited retroperitoneal space. The aim of our study was to prospectively assess the effect of LTA versus PRA laparoscopic adrenalectomies on renal function. MATERIAL AND METHODS: We randomly assigned patients referred for unilateral adrenalectomy to either LTA (n = 33) or PRA (n = 44). The inclusion criteria were: hormonal activity and/or tumour diameter > 4 cm and/or suspicion of metastasis to adrenal gland. The exclusion criteria comprised: tumours > 8 cm, results of imaging studies suggesting primary invasive malignancy, and refusal to undergo randomisation. The patients were prospectively followed for a minimum of six months. Serum creatinine, cystatin C, and urinary neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively and at postoperative days: 1, 7, and 30. RESULTS: We found increased concentrations of urinary NGAL at day 1 following laparoscopic adrenalectomy using PRA, as compared to LTA. Patients undergoing right-sided PRA had increased creatinine concentrations, as compared to left-sided PRA. Patients with aldosterone-producing adenoma had decreased preoperative eGFR as compared to subjects with non-functioning incidentaloma. NGAL increased significantly in this group postoperatively. All the disturbances normalised within one month postoperatively. CONCLUSIONS: Renal function impairment after PRA may result from compression of inferior vena cava by high retroperitoneal pressure during right-sided adrenalectomy. Despite the transient character of the observed abnormalities, we suggest that patients with high risk of acute kidney injury may benefit from an alternative technique of adrenalectomy using LTA.

Laparoscopic adrenalectomy: lateral transperitoneal versus posterior retroperitoneal approach - prospective randomized trial.

INTRODUCTION: Laparoscopic adrenalectomy has become the gold standard of surgical treatment for benign adrenal masses. Two alternative surgical approaches are currently advocated: the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). Several randomized trials have compared LTA to PRA, but most of them included small numbers of patients or had stringent inclusion criteria. AIM: To compare clinical results of LTA and PRA endoscopic adrenalectomies for tumors < 8 cm with wide inclusion criteria. MATERIAL AND METHODS: We randomized 77 patients to either LTA (n = 33) or PRA (n = 44). The groups were comparable in terms of age, gender proportions, body mass index, tumor size, clinical and pathological diagnosis. We analyzed duration of surgery, intraoperative blood loss, postoperative pain, length of hospital stay and postoperative morbidity. RESULTS: The follow-up concerned 98.8% of patients and was on average 28 (8-47) months long. There were no conversions. We identified significantly lower intensity of pain assessed 24 h after surgery in the PRA group (3.4 ±1), as compared to LTA (4.2 ±1), with lower prevalence of shoulder pain (2.3% vs. 30.3%, respectively). Postoperative hospital stay was shorter in the PRA (1.14 ±0.4) than in the LTA (1.36 ±0.5) group. Perioperative morbidity concerned 4 patients in each group with pain requiring oral analgesia > 7 days. CONCLUSIONS: To our knowledge this is the largest prospective randomized study comparing LTA to PRA. We demonstrated safety, efficacy and very low morbidity of both techniques. The PRA proved superior to LTA in terms of lower intensity of postoperative pain and shorter hospital stay.

A Comparison of Two Approaches to Laparoscopic Adrenalectomy: Lateral Transperitoneal Versus Posterior Retroperitoneal Approach.

BACKGROUND: Laparoscopic adrenalectomy is the gold standard for the surgical treatment of benign adrenal masses. It is most commonly performed using the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). The choice of the method depends on contraindications for a particular approach in an individual case and surgical experience. The objective of the article is to compare two approaches, LTA and PRA, in view of our own experience and literature review. OBJECTIVES: The objective of the article is to compare two approaches, LTA and PRA, in view of our own experience and literature. MATERIAL AND METHODS: The assessment involved morphological characteristics of tumors, indications for PRA and LTA, operative time, perioperative blood loss and postoperative complications. RESULTS: Seventy-seven of the examined 104 laparoscopic adrenalectomies were performed retroperitoneally; 27 - transperitoneally. The mean size of tumors in PRA was 4.6 cm and in LTA 6.2 cm. The mean total operative time was 91.8 min in the case of PRA and 153.1 min in LTA. No differences in the amount of blood loss between the two approaches were recorded. The average hospitalization post PRA lasted 2.03 days and post LTA 2.67 days. CONCLUSIONS: Laparoscopic adrenalectomy proves to be an effective and safe surgical technique both in the case of LTA and PRA. The technique to be used should be suited to surgical team's experience, patient's general condition and tumor size and location. In our experience, the most advantageous approach in the case of tumors of less than 7 cm is PRA.

Mesenteric lymphadenitis caused by Yersinia enterocolitica.

Yersiniosis is an acute or chronic, zoonotic disease caused by infection of Gram-negative rods Yersinia enterocolitica. It can be transmitted by the consumption of originally contaminated food products (pork, unpasteurized milk) or secondarily contaminated with animal or vegetable products. The clinical picture of infection may have a variable course is related to the age and physical condition of the patient, or pathogenic properties of microorganisms. Infection caused by Y. enterocolitica can occur in different clinical forms: food poisoning, colitis, mesentric lymphadenitis, erythema nodosum, arthritis, pharyngitis, pneumonia, meningitis, sepsis. The aim of this study was to present a rare case of infection with Y. enterocolitica mesenteric lymph nodes coexistent with appendicitis.

Videoscopic adrenalectomy - when does retroperitoneal seem better?

INTRODUCTION: Videoscopic adrenalectomy is the gold standard for the surgical treatment of benign adrenal tumours. The two most common approaches are the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). So far it has not been established which is the preferable one. The choice depends primarily on the surgeon's preference and contraindications for a particular approach in individual cases. AIM: To compare the two most common approaches for videoscopic adrenalectomy, LTA and PRA, based on a literature review and our own experience. MATERIAL AND METHODS: We reviewed the literature (PubMed and Cochrane 1990 - current) and analysed retrospectively our own patients who underwent videoscopic adrenalectomy between 2009 and 2013. The analysis covered patient features, tumour characteristics, reasons for qualification for each approach, operative time and postoperative complications. RESULTS: Out of 71 videoscopic adrenalectomies, 50 were performed using PRA and 21 using LTA. Patients in the PRA group on average were older, but had smaller tumours. There was no significant difference in perioperative morbidity between PRA and LTA. Mean blood loss and total operative time were smaller/shorter for the PRA group in comparison to the LTA group. Time to first oral intake and the average postoperative hospital stay were shorter for PRA than LTA. CONCLUSIONS: Videoscopic adrenalectomy is a safe and efficient technique performed using both LTA and PRA approaches. The choice of technique should be guided, most of all, by surgeon experience, patient characteristics, tumour size and location. Our preferable approach is PRA, especially for small (< 6 cm) benign tumours. We find LTA advantageous for tumours of larger size, with suspected malignant character (either primary or secondary), in ectopic position, as well as in patients lacking an ipsilateral kidney or when a simultaneous abdominal operation is planned.

Epidermal cyst of the spleen--a rare case in clinical practice.

Splenic cysts are rare disease that are diagnosed incidentally during imaging studies. In recent years, through the development of diagnostic methods the detection of their are increased, although documented and described in the literature of cases is still low. The disease can be asymptomatic--this concerns mainly small cysts, but greater changes cause unspecific symptoms resulting from oppression of enlarged spleen on adjacent organs. Due to the etiology of cysts, they are divided into primordial and false. Primordial cysts have an epithelial lining which distinguishes them from false and they are divided into parasitic and nonparasitic. Because of the possibility of complications cysts usually treated surgically, with the aim to preserve the splenic parenchyma. We present a case of a 28-year-old woman who has revealed the presence of epidermal cysts of the spleen.

Neuroendocrine tumors of the pancreas.

The neuroendocrine tumors (NET) of the pancreas are very rare lesions with frequency of about 3 to 10 per 1 000 000 inhabitants. The neuroendocrine tumors composes a heterogeneous group of tumors. The gastro-entero-pancreatic tumors (GEP) constitute 70% of all NET and 2% of all digestive system tumors. There have been several attempts to classify those lesions and since 2000 exists WHO classification which divides NET according to malignancy and histologic structure. The most often NET of the pancreas are insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma. There is a recommendation to assay hormonal activity, measure concentration of specific peptides, biogenic amines and hormones produced by NET cells to establish diagnosis. Those tests are useful in monitoring treatment and in prognostication course of the disease. Imaging methods especially useful in localization GEP-NET are: ultrasound (US), endoscopic ultrasound (EUS), somatostatin receptor scintigraphy (SRS), computer tomography (CT), magnetic resonance (MR) and angiography. The most sensitive method in preoperative diagnosis seems to be EUS or less accessible intra ductal ultrasonography (IDUS). Surgical treatment depends on progression of disease as well as on localization of tumor and consists in both radical methods and palliative operations. The gold standard in pharmacological treatment are somatostatin analogs which can induce long-term remission even in inoperable lesions. Although NET of pancreas are very rare. they are still important diagnostic and therapeutic problem and requires interdisciplinary co-operation. The neuroendocrine tumors should be treated in centers with highest rank of references.

[Preliminary outcomes of laparoscopic adjustable gastric banding and Roux-en-Y gastric bypass in surgical obesity treatment]. / Wstepne wyniki chirurgicznego leczenia otylosci metoda regulowanej opaski zollakowej i zespolenia omijajacego zoladkowo-jelitowego z petla Roux-en-Y.

UNLABELLED: Obesity is an increasing medical and social problem. Besides conservative therapy, resulting in modest weight loss, the available treatment option is bariatric surgery. Surgery is recommended for patients with BMI > 40 or > 35 with comorbidities such as diabetes, hypertension, osteoarthritis and poor quality of life. THE AIM OF THIS STUDY: Evaluation of early outcomes and comparison the most often performed surgical procedures in treatment of obesity such as Roux-en-Y Gastric Bypass (RYGB) and Laparoscopic Adjustable Gastric Banding (LAGB). MATERIAL AND METHODS: For this retrospective study we reviewed 26 patients treated surgically in our Department because of obesity between 2005 and 2006. There were 12 women and 14 men, ranging in age from 21 to 59 (median--41), BMI from 41 to 52 (median--45.5). RESULTS: Patients were discharged on 2 day after LAGB and between 6 and 8 day after RYGB. Postoperative complications were noted in 3 patients. The first patient suffered from recurrent postoperative infection combined with abscess of abdominal wall. The treatment prolonged to 6 months and resulted in postoperative hernia. Finally he was operated once more and elongation of Roux limb was performed because of stopped weight loss. The operation of abdominal hernia in this case was performed at the same time. The second complication was band slippage with high obstruction 4 months after LAGB and the gastric band was removed. In the third patient pneumonia and pyothorax 7 days after LAGB was diagnosed. Noted weight loss 6 months after operations was from 9 to 25 kg after LAGB and from 17 to 38 kg after RYGB. CONCLUSIONS: In our opinion bariatric surgery is the most efficient option to achieve weight loss in morbid obesity. Bariatric operations are characterized with relative low rate of complications. LAGB is shorter procedure and its risk is lower than RYGB, moreover after LAGB the anatomy of digestive tract is not modified and it is easy to remove gastric band when necessary.