Systemic Inflammatory Markers as Predictors of Postoperative Complications and Survival in Patients With Advanced Head and Neck Squamous Cell Carcinoma Undergoing Free-Flap Reconstruction.

PURPOSE: The aim of this study was to determine the prognostic value of systemic inflammatory indices as factors for postoperative complications and survival in patients with advanced stages of p16-negative head and neck squamous cell carcinoma undergoing free-flap reconstruction. METHODS: This was a retrospective cohort study. The primary predictor variables were inflammatory markers such as neutrophil, lymphocyte, monocyte, and platelet count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, lymphocyte-monocyte ratio, derived NLR, systemic immune-inflammatory index, and systemic inflammatory marker index (SIM). Multivariate regression analyses were used to measure the associations between systemic inflammatory indices and overall and disease-free survival as a primary outcome and occurrence of postoperative complications as a secondary outcome measure. RESULTS: The sample was composed of 69 male (76.67%) and 21 female (23.33%) patients, with an average age of 61.15 ± 9.79 years. The median follow-up time was 24 months, and 73 of 91 (66.43%) patients were alive during the median follow-up. Overall disease survival correlated with systemic immune-inflammation (P = .022, cutoff >1,005.3, sensitivity 67.1%, and specificity 70.6%) and SIM (P = .0001, cutoff >4.05, sensitivity 90.4%, and specificity 41.2%), preoperative platelets (P = .036, cutoff <194, sensitivity 28.8%, and specificity 94.1%), and postoperative lymphocytes (P = .012, cutoff <0.6, sensitivity 38%, and specificity 76.5%), whereas increased SIM (P = .042, cutoff >4.05, sensitivity 91.3%, and specificity 38.1%), NLR (P = .031, cutoff >13.2, sensitivity 56.9%, and specificity 60%), and preoperative platelets (P = .006, cutoff <244, sensitivity 52.3%, and specificity 76%) were associated with adverse disease-free survival. The cumulative postoperative complication rate was 34.5%, of which 13.3% accounted for major complications, whereas derived NLR (P = .013, degrees of freedom 1, χ2 test 6.161, cutoff >2.3) and postoperative lymphocytes (P = .009, DF 1, χ2 test 6.756, cutoff <1) correlated with occurrence of complications. CONCLUSIONS: Inflammatory indices as measures of inflammation-related systemic dysfunction may be associated with adverse survival in patients with head and neck squamous cell carcinoma and occurrence of postoperative complications and with specific cutoff values.

The Role of Folded Multi-Island Vertical Rectus Abdominis Myocutaneous Flap in Reconstruction of Complex Maxillectomy and Midfacial Defects.

ABSTRACT: The rationale and outcomes for reconstruction of complex maxillectomy and midfacial defects using a folded multi-island vertical rectus abdominis myocutaneous free flap (MI-VRAM) are analyzed in this study.A retrospective review of prospectively collected database was conducted on all VRAM free flaps used in head and neck reconstruction from 2013 to 2019. A total of 39 cases were identified, of which 21 patients underwent immediate VRAM flap reconstruction for complex maxillectomy and midfacial defects. Variables including age, sex, pathologic subtypes, tumor staging, type of resection, defect classification, adjuvant therapy, complications, follow-up time, and reconstructive details were collected.Single skin-island VRAM was used in 10 (47.6%) patients. Eleven (52.4%) patients required the use of folded MI-VRAM flap. In 6 (28.6%) patients a triple skin-island VRAM was used and 5 (23.8%) received a double skin-island VRAM. The average size of harvested skin paddle was 15 × 7.2 cm. Secondary flap contouring was required in 6 (28.6%) patients. There were no cases of total flap loss and no major donor site complications recorded.Folded MI-VRAM flap is a reliable method for reconstruction of complex maxillectomy and midfacial defects. It provides multiple independent skin islands with excellent plasticity and abundant volume of tissue for restoration of facial contours.

Significance of Anthropometric and Nutritive Factors in Oral and Oropharyngeal Cancer Patients Undergoing Free Flap Reconstruction.

PURPOSE: This study analyzed associations between preoperative nutritional status and the incidence of early postoperative complications as a primary outcome in patients with oral and oropharyngeal cancer undergoing free flap reconstruction. We hypothesized that preoperative nutritional status may be linked with specific complications, allowing for better preoperative risk assessment. PATIENTS AND METHODS: This longitudinal, retrospective cohort study encompassed 113 patients, all treated surgically for oral and oropharyngeal cancer in the period from March 2013 up to March 2018 in a tertiary referral center. Variables considered were preoperative and postoperative serum albumin and protein values; body mass index; waist-to-hip ratio; circumference of the neck, waist, hip, and thigh; number of cigarettes smoked per day during the 10-year period before surgery; average alcohol consumption; operative time; and postoperative albumin administration. RESULTS: Our study identified preoperative protein serum concentration (≤62 g/L), postoperative albumin administration (≥200 mL), number of cigarettes smoked per day (>20), and prolonged operative time (≥450 minutes) to be associated with postoperative complications. CONCLUSIONS: This is the first study reporting cutoff values of clinical significance in assessing patient preoperative nutritional status in light of reducing postoperative complications after free flap reconstruction.

TYPE II HYPOPHARYNGEAL DEFECT RECONSTRUCTION - A SINGLE INSTITUTION EXPERIENCE.

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

Remission of Graves' disease is not related to early restoration of euthyroidism with high-dose methimazole therapy.

UNLABELLED: Introduction and aims: The most recent hypothesis postulated that early restoration of euthyroid state in patients with Graves' disease changes the course of the disease and leads to better disease control. Therefore, we analyzed the efficacy of methimazole therapy and the course of disease in patients with restored euthyroidism and in patients with active disease on first control visit. PATIENTS AND METHODS: We included 63 patients with total T4 level >190 nmol/L or T3 >7 nmol/L and diffuse goiter with no previous episodes of hyperthyroidism. All patients received initially high doses of methimazole (60-80 mg) followed by a rapid dose reduction. RESULTS: Ten percent of patients were excluded from the study due to side effects. Two different groups emerged after 5 weeks of treatment with same dose of methimazole: group 1 with active disease (48%) and group 2 with restored euthyroidism. Further controls on 12th, 24th and 68th weeks of treatment showed no difference in remission rates, number of iatrogenic hypothyroid episodes, and number of exacerbations between the two groups, regardless of methimazole dose. There was no association between age, gender, thyroid hormone levels, and remission and exacerbation rates. CONCLUSIONS: Initially, higher methimazole doses with rapid progressive decrease to maintenance dose result in similar remission rates and are followed by similar incidence of adverse side-effect as fixed low dose therapy. Our results indicate that neither an early restoration of euthyroidism nor the difference in methimazole doses influence the course of Graves' disease.

Sex- and Site-Related Significance in Cutaneous Head and Neck Melanoma.

Cutaneous head and neck melanoma is a separate subgroup of cutaneous melanoma that has a worse prognosis than other primary sites. The aim of this article is to examine the significance of sex and site of primary lesion as additional risk factors. Primary localization distribution and metastatic disease in the neck in a retrospective cohort of 159 patients with cutaneous head and neck malignant melanoma were analyzed. Men develop primary melanoma more frequently than women in the left peripheral head and neck regions (P = .0364), as well as clinically visible and occult metastatic disease in the left side of the neck (P = .0138). Patients with clinically occult regional metastatic disease showed a significantly poorer survival rate than the rest of the group that underwent elective neck dissections (P = .0270). Left-sided disease in male patients may be an additional risk factor in cutaneous head and neck melanoma. Performing elective neck dissections in high-risk patients might identify patients with occult metastatic disease and worse prognosis but does not offer any significant therapeutic benefit.

Decreased sensitivity of thyrotropin-thyroid hormone feedback control in hypothyroid and athyreotic patients treated with levothyroxine. Is serum triiodothyronine involved?

OBJECTIVES: The search for optimal therapy for hypothyroidism is challenging and complex and is still going on. We investigated TSH-thyroid hormone feedback control in hypothyroid and athyreotic patients properly treated with levothyroxine (LT4), based on normal TSH values. MATERIAL AND METHODS: We randomly selected 150 hypothyroid, 110 athyreotic and 210 euthyroid subjects, determined their serum T4, T3 and TSH values and calculated T4/TSH and T3/T4 ratios. RESULTS: The TSH distribution in hypothyroidism was significantly shifted to the higher and that in athyreosis to the lower values from the normal distribution in euthyroid controls. This TSH-thyroid hormone dissociation in hypothyroidism was characterized with higher T4 and higher matched TSH values. We found 5% hypothyroid and 10% athyreotic patients normalize TSH only with hyperthyroxinemia. Serum T3 was lower in both hypothyroid groups and unaffected by a higher LT4 dose and higher serum T4 in athyreosis. CONCLUSION: Our results suggest that the decreased serum T3 is a major cause of impaired TSH-thyroid hormone feedback control in hypothyroidism treated with LT4.

Thyrotropin and thyroid hormone economy in euthyroid Hashimoto's thyroiditis.

Little is known about thyrotropin (TSH) and thyroid hormones in euthyroid Hashimoto's thyroiditis (HT), thus the aim was to investigate TSH and thyroid hormone economy in euthyroid HT and its relation to thyroid function. Ninety-five patients with euthyroid HT with normal TSH and thyroid hormones on the last follow up between 2009 and 2011 were investigated. Previous observation period ranged from 1.5 to 4.8 (mean 2.8) years, and they had never been treated with levothyroxine. The results of TSH and thyroid hormones were compared with 210 healthy subjects and expressed as median (25%-75%). According to TSH value, the subjects were divided into quartiles: TSH 0.4-0.99 (1q), 1.0-1.99 (2q), 2.0-2.99 (3q) and 3.0-4.0 mIU/L (4q). Euthyroid HT patients had higher TSH (2.53 [1.79-3.14] vs.1.95 [1.24-2.72], p < 0.001). T4 and T3 were not different. The distribution of TSH in HT patients was significantly shifted to the right; 71% of patients were in the 3q and 4q groups. When HT patients with higher TSH (3q and 4q) were compared with those with lower TSH (1q and 2q), significant differences emerged in TSH (3.01 [2.48-3.48] vs.1.45 [1.07-1.71] mIU/L), T4 (99.0 [88.2-112.0] vs.112.0 [105.0-122.0] nmol/L) and T3 (1.78 [1.48-2.05] vs. 2.10 [1.85-2.21] nmol/L; p < 0.01). TPO values were similar in both groups. A gradually increasing proportion of euthyroid HT patients with at least one supranormal TSH during the observation period were found: 0% in 1q, 10% in 2q, 15% in 3q and 44% in 4q TSH group. Euthyroid HT patients maintain euthyroidism only under strenuous TSH stimulation. The patients with high normal TSH are identified as those with a major risk of hypothyroidism in the near future.

Ultrasound measurement of the volume of musculus quadriceps after knee joint injury.

The monitoring of the recovery of femoral muscles, after the knee-joint injury, is possible by the method of ultrasound measurement of the muscular volume. In a clearly defined longitudinal study, our object was to standardize the method of ultrasound measurement of muscular volume and to evaluate its adequacy in practical application in quadriceps muscle rehabilitation. The ultrasound measurements of m. rectus femoris and m. vastus intermedius were conducted in three intervals: in the first 24 hours after the injury; after 1 week, when immobilization was removed; and after 6 weeks, when rehabilitation was finished. The study comprised 30 patients with knee-joint injury, and 30 asymptomatic subjects, who formed the control group. The results showed significant decrease of muscular volume (mm3) after joint immobilization on injured leg and a significant increase of volume after rehabilitation. The same differences were observed on healthy legs, but without significance. Within the same intervals, there were no changes in the muscular mass in the control group. M. rectus femoris was completely recovered in greater number of patients (54.1%), comparing to m. vastus intermedius (25.4%). We conclude that the ultrasound is an appropriate method for monitoring the process of muscular atrophy during immobilization, as well as the course of muscular restitution during the physical therapy.

Incidentally elevated thyrotropin in otherwise properly treated hypothyroid patients does not require higher levothyroxine dose.

In 20 properly treated hypothyroid patients with normal thyrotropin (TSH) values during previous observation, TSH was incidentally mildly/moderately elevated (4.5-8.0 mIU/L; normal values 0.4-4.0) on the last follow up. However, they were continuously treated with the same levothyroxine (LT4) dose (mean: 95 µg) and six months later all TSH values normalized. The authors suggest that the physicians, in response to incidentally increased TSH value in otherwise properly treated hypothyroid patients, refrain from prompt increasing the LT4 dose unless TSH values are persistently elevated or/and progressing.

Do we treat hypothyroidism properly? A survey of 2488 patients from University Hospital Center, Zagreb, Croatia.

OBJECTIVES: The objective was to examine the effectiveness of levothyroxine treatment in hypothyroid patients in achieving normal thyroid stimulating hormone (TSH), T4 and T3. MATERIAL AND METHODS: Results of the treatment of 2448 hypothyroid patients treated with LT4 for at least 12 months between 2006 and 2011 (1920 with spontaneous hypothyroidism and 528 with hypothyroidism following surgery or 131I) are presented. Serum TSH, T4 and T3 were analyzed and referred as normal, increased or decreased. RESULTS: Normal TSH was found in 75 and 68% of patients respectively. In subgroups with increased TSH, 15% and 14% of patients showed borderline or only mildly increased TSH (4.1-5.5 mIU/L). T4 (94 and 86%) and T3 (93 and 90% respectively) were normal in the majority of patients from both groups. LT4 over-treatment is observed in only 4 and 6% of patients respectively. CONCLUSION: The results are less favorable for the group with hypothyroidism following surgery or (131)I than in spontaneous hypothyroidism, but in about 90% of patients with spontaneous hypothyroidism and 82% with hypothyroidism following surgery or (131)I, the LT4 dose could remain unchanged. It is discussed whether standard LT4 replacement could render normal TSH and thyroid hormone patterns in all hypothyroid patients.

Brain tumor as a prototype of severe brain lesion in patients with "low T3 syndrome".

The purpose of our study was to contribute to better understanding of cerebrospinal fluid (CSF) as a valuable biological material in the research of brain tumors within the "low T3 syndrome", and to discuss the role of thyroid hormones in the central nervous system in subjects with severe cerebral lesions. We studied the levels of total triiodothyronine (tT3), total thyroxine (tT4), free triiodothyronine (fT3), free thyroxine (fT4), reverse triiodothyronine (rT3) and thyrotropin (TSH) in serum, and fT3, fT4, rT3 and TSH levels in CSF of patients with brain tumor, and compared the results with control group. Study results indicated a statistically significantly higher level of rT3 in serum and CSF of brain tumor patients vs. control group (p < 0.05). The rT3/fT3 ratio was highest in CSF and serum of brain tumor patients, yielding a statistically significant difference (p < 0.05). These results could suggest higher permeability of the blood-brain barrier in brain tumor patients. We also assume that rT3, in the framework of"cerebral low T3 syndrome", is also generated through local intracerebral conversion. Disruption of this process in severe cerebral lesion can lead to increased rT3 concentrations, i.e. development of the "low T3 syndrome".

Development of Graves' disease following radioiodine treatment for autonomously functioning thyroid adenoma: case report.

A patient with development of autoimmune hyperthyroidism following radioiodine treatment for autonomously functioning thyroid adenoma is presented. This is a rare occurrence, probably as a consequence of shedding of the thyroid-stimulating hormone receptor, which is a source of antigen leading to activation of the autoimmune response in susceptible individuals.

Why does the patient with Graves' disease remain euthyroid/mildly hyperthyroid following total thyroidectomy--the role of thyrotropin receptor antibodies (TRAb) and vestigial remnants of the thyroglossal tract.

A young female patient suffering from Graves' disease is presented, who raised some diagnostic and therapeutic dilemmas after being diagnosed with subclinical hyperthyroidism following total thyroidectomy. This 20-year-old female patient, carrier of HLA B8 DR3 genes, was referred to our hospital for total thyroidectomy after developing severe leukopenia on both methimazole and propylthiouracil therapy. A high postoperative titer of thyrotropin receptor antibodies and positive scintigraphy finding of the pyramidal lobe and remnant thyroid tissue in the left thyroid lobe led to the administration of radioiodine. Despite further enlargement of the remnant thyroid tissue on post-radioiodine scintiscanning, the patient is currently euthyroid, with normal thyroid-stimulating hormone levels; however, her long-term prognosis remains uncertain.