Ultrasound characteristics of follicular and parafollicular thyroid neoplasms: diagnostic performance of artificial neural network.

BACKGROUND: Ultrasound is the first-line imaging modality for detection and classification of thyroid nodules. Certain features observable by ultrasound have recently been equated with potential malignancy. This retrospective cohort study was conducted to test the hypothesis that radiomics of the four categorical divisions (medullary [MTC], papillary [PTC], or follicular [FTC] carcinoma and follicular thyroid adenoma [FTA]) demonstrate distinctive sonographic characteristics. Using an artificial neural network model for proof of concept, these sonographic features served as input. METHODS: A total of 148 patients were enrolled for study, all with confirmed thyroid pathology in one of the four named categories. Preoperative ultrasound profiles were obtained via standardized protocols. The neural network consisted of seven input neurons; three hidden layers with 50, 250, and 100 neurons, respectively; and one output layer. RESULTS: Radiomics of contour, structure, and calcifications differed significantly according to nodule type (p = 0.025, p = 0.032, and p = 0.0002, respectively). Levels of accuracy shown by artificial neural network analysis in discriminating among categories ranged from 0.59 to 0.98 (95% confidence interval [CI]: 0.57-0.99), with positive and negative predictive ranges of 0.41-0.99 and 0.78-0.97, respectively. CONCLUSIONS: Our data indicate that some MTCs, PTCs, FTCs, and FTAs have distinctive sonographic characteristics. However, a significant overlap of these characteristics may impede an explicit classification. Further prospective investigations involving larger patient and nodule numbers and multicenter access should be pursued to determine if neural networks of this sort are beneficial, helping to classify neoplasms of the thyroid gland.

Pelvic Intraoperative Neuromonitoring Prevents Dysfunction in Patients With Rectal Cancer: Results From a Multicenter, Randomized, Controlled Clinical Trial of a NEUROmonitoring System (NEUROS).

OBJECTIVE: This NEUROmonitoring System (NEUROS) trial assessed whether pelvic intraoperative neuromonitoring (pIONM) could improve urogenital and ano-(neo-)rectal functional outcomes in patients who underwent total mesorectal excisions (TMEs) for rectal cancer. BACKGROUND: High-level evidence from clinical trials is required to clarify the benefits of pIONM. METHODS: NEUROS was a 2-arm, randomized, controlled, multicenter clinical trial that included 189 patients with rectal cancer who underwent TMEs at 8 centers, from February 2013 to January 2017. TMEs were performed with pIONM (n=90) or without it (control, n=99). The groups were stratified according to neoadjuvant chemoradiotherapy and sex, with blocks of variable length. Data were analyzed according to a modified intention-to-treat protocol. The primary endpoint was a urinary function at 12 months after surgery, assessed with the International Prostate Symptom Score, a patient-reported outcome measure. Deterioration was defined as an increase of at least 5 points from the preoperative score. Secondary endpoints were sexual and anorectal functional outcomes, safety, and TME quality. RESULTS: The intention-to-treat analysis included 171 patients. Marked urinary deterioration occurred in 22/171 (13%) patients, with significantly different incidence between groups (pIONM: n=6/82, 8%; control: n=16/89, 19%; 95% confidence interval, 12.4-94.4; P =0.0382). pIONM was associated with better sexual and ano-(neo)rectal function. At least 1 serious adverse event occurred in 36/88 (41%) in the pIONM group and 53/99 (54%) in the control group, none associated with the study treatment. The groups had similar TME quality, surgery times, intraoperative complication incidence, and postoperative mortality. CONCLUSION: pIONM is safe and has the potential to improve functional outcomes in rectal cancer patients undergoing TME.

DOG1 overexpression is associated with mismatch repair deficiency and BRAF mutations but unrelated to cancer progression in colorectal cancer.

INTRODUCTION: The transmembrane channel protein DOG1 (Discovered on GIST1) is normally expressed in the gastrointestinal interstitial cells of Cajal and also in gastrointestinal stroma tumors arising from these cells. However, there is also evidence for a relevant role of DOG1 expression in colorectal cancers. This study was undertaken to search for associations between DOG1 expression and colon cancer phenotype and key molecular alterations. METHODS: A tissue microarray containing samples from more than 1,800 colorectal cancer patients was analyzed by immunohistochemistry. RESULTS: DOG1 immunostaining was detected in 503 (30.2%) of 1,666 analyzable colorectal cancers and considered weak in 360 (21.6%), moderate in 78 (4.7%), and strong in 65 (3.9%). Strong DOG1 immunostaining was associated with advanced pT stage (p=0.0367) and nodal metastases (p=0.0145) but these associations were not retained in subgroups of 1,135 mismatch repair proficient and 86 mismatch repair deficient tumors. DOG1 positivity was significantly linked to several molecular tumor features including mismatch repair deficiency (p=0.0034), BRAF mutations (p<0.0001), nuclear p53 accumulation (p=0.0157), and PD-L1 expression (p=0.0199) but unrelated to KRAS mutations and the density of tumor infiltrating CD8 positive lymphocytes. CONCLUSION: Elevated DOG1 expression is frequent in colorectal cancer and significantly linked to important molecular alterations. However, DOG1 overexpression is largely unrelated to histopathological parameters of cancer aggressiveness and may thus not serve as a prognostic parameter for this tumor entity.

High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer.

BACKGROUND: Immune checkpoint-inhibitors targeting the PD-1/PD-L1 system are FDA approved in microsatellite instable (MSI) or mismatch repair deficient (dMMR) colorectal cancer (CRC). PD-L1 expression is tightly linked to features connected to immune checkpoint inhibitor response, but studies on large subsets of cancers analyzing the correlation between different status of MSI/dMMR, tumor infiltrating lymphocytes and PD-L1 expression are still lacking. METHODS: More than 1800 CRC were analyzed for PD-L1 by immunohistochemistry in a tissue microarray format. Data were compared to MMR, the number of intratumoral CD8+ cytotoxic T-cells, and adverse clinico-pathological parameters. Different cutoff levels for defining PD-L1 positivity in tumor cells (1%, 5%, 10%, and 50%) yielded comparable results. RESULTS: At a cutoff level of 5%, PD-L1 positivity was seen in 5.1% of tumors. PD-L1 was more often positive in dMMR (18.6%) than in MMR proficient (pMMR) cancers (4.1%; p < 0.0001). The number of intratumoral CD8+ lymphocytes was strikingly higher in PD-L1 positive (939.5 ± 118.2) than in PD-L1 negative cancers (310.5 ± 24.8). A higher number of intratumoral CD8+ lymphocytes was found in dMMR CRC (PD-L1 positive: 1999.7 ± 322.0; PD-L1 negative: 398.6 ± 128.0; p < 0.0001) compared to pMMR CRC (PD-L1 positive: 793.2 ± 124.8; PD-L1 negative: 297.2 ± 24.2; p < 0.0001). In dMMR and pMMR CRC, PD-L1 expression in tumor cells was unrelated to tumor stage, lymph node status or lymphatic/venous invasion. PD-L1 positivity in tumor associated immune cells was seen in 47.5% of cases and was significantly linked to high numbers of tumor infiltrating CD8+, low tumor stage, and absence of lymph node metastasis and lymphatic/venous invasion (p < 0.0001 each). CONCLUSION: The data support the previously suggested fact that PD-L1 expression in tumor cells is driven by extensive cytotoxic T-cell infiltration in highly immunogenic dMMR and pMMR CRC. Frequent and intense PD-L1 expression in tumor cells of dMMR CRC may contribute to the high response rates of dMMR CRC to immune checkpoint-inhibitors.

Advanced thyroid carcinomas: neural network analysis of ultrasonographic characteristics.

BACKGROUND: Ultrasound is the first-line imaging modality for detection and classification of thyroid nodules. Certain characteristics observable by ultrasound have recently been identified that may indicate malignancy. This retrospective cohort study was conducted to test the hypothesis that advanced thyroid carcinomas show distinctive clinical and sonographic characteristics. Using a neural network model as proof of concept, nine clinical/sonographic features served as input. METHODS: All 96 study enrollees had histologically confirmed thyroid carcinomas, categorized (n = 32, each) as follows: group 1, advanced carcinoma (ADV) marked by local invasion or distant metastasis; group 2, non-advanced papillary carcinoma (PTC); or group 3, non-advanced follicular carcinoma (FTC). Preoperative ultrasound profiles were obtained via standardized protocols. The neural network had nine input neurons and one hidden layer. RESULTS: Mean age and the number of male patients in group 1 were significantly higher compared with groups 2 (p = 0.005) or 3 (p <  0.001). On ultrasound, tumors of larger volume and irregular shape were observed significantly more often in group 1 compared with groups 2 (p <  0.001) or 3 (p ≤ 0.01). Network accuracy in discriminating advanced vs. non-advanced tumors was 84.4% (95% confidence interval [CI]: 75.5-91), with positive and negative predictive values of 87.1% (95% CI: 70.2-96.4) and 92.3% (95% CI: 83.0-97.5), respectively. CONCLUSIONS: Our study has shown some evidence that advanced thyroid tumors demonstrate distinctive clinical and sonographic characteristics. Further prospective investigations with larger numbers of patients and multicenter design should be carried out to show whether a neural network incorporating these features may be an asset, helping to classify malignancies of the thyroid gland.

Ultrasound Imaging of Cervical Anatomic Variants.

Embryologic developmental variants of the thyroid and parathyroid glands may cause cervical anomalies that are detectable in ultrasound examinations of the neck. For some of these developmental variants, molecular genetic factors have been identified. Ultrasound, as the first-line imaging procedure, has proven useful in detecting clinically relevant anatomic variants. The aim of this article was to systematically summarize the ultrasound characteristics of developmental variants of the thyroid and parathyroid glands as well as ectopic thymus and neck cysts. Quantitative measures were developed based on our findings and the respective literature. Developmental anomalies frequently manifest as cysts that can be detected by cervical ultrasound examinations. Median neck cysts are the most common congenital cervical cystic lesions, with a reported prevalence of 7% in the general population. Besides cystic malformations, developmental anomalies may appear as ectopic or dystopic tissue. Ectopic thyroid tissue is observed in the midline of the neck in most patients and has a prevalence of 1/100,000 to 1/300,000. Lingual thyroid accounts for 90% of cases of ectopic thyroid tissue. Zuckerkandl tubercles (ZTs) have been detected in 55% of all thyroid lobes. Prominent ZTs are frequently observed in thyroid lobes affected by autoimmune thyroiditis compared with normal lobes or nodular lobes (P = 0.006). The correct interpretation of the ultrasound characteristics of these variants is essential to establish the clinical diagnosis. In the preoperative assessment, the identification of these cervical anomalies via ultrasound examination is indispensable.

Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer.

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p < 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (p < 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (p < 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness.

Total Versus Near-total Thyroidectomy in Graves Disease: Results of the Randomized Controlled Multicenter TONIG-trial.

BACKGROUND: Previous data suggest that the incidence of hypoparathyroidism after surgery for Graves disease (GD) is lower after subtotal thyroidectomy compared to total thyroidectomy (TT). The present study evaluated the incidence of postoperative hypoparathyroidism after near-total (NTT) versus TT in GD. METHODS/DESIGN: In a multicenter prospective randomized controlled clinical trial, patients with GD were randomized intraoperatively to NTT or TT. Primary endpoint was the incidence of transient postoperative hypoparathyroidism. Secondary endpoints were permanent hypoparathyroidism, transient recurrent laryngeal nerve palsy (RLNP), reoperations for bleeding, inadvertently removed parathyroid glands, and recurrent hyperthyroidism after 12 months. RESULTS: Eighteen centers randomized 205 patients to either TT (n = 102) or NTT (n = 103) within 16 months. According to intention-to-treat postoperative transient hypoparathyroidism occurred in 19% (20/103) patients after NTT and in 21% (21 of 102) patients after TT (P = 0.84), which persisted >6 months in 2% and 5% of the NTT and TT groups (P = 0.34). The rates of parathyroid autotransplantation (NTT 24% vs TT 28%, P = 0.50) and transient RLNP (NTT 3% vs TT 4%, P = 0.35) was similar in both groups. The rate of reoperations for bleeding tended to be higher in the NTT group (3% vs 0%, P = 0.07) and the rate of inadvertently removed parathyroid glands was significantly higher after NTT (13% vs 3%, P = 0.01). An existing endocrine orbitopathy improved in 35% and 24% after NTT and TT (P = 0.61). Recurrent disease occurred in only 1 patient after TT (P = 0.34). CONCLUSION: NTT for GD is not superior to TT regarding transient postoperative hypoparathyroidism.

MIBI scintigraphy of parathyroid adenomas: correlation with biochemical and histological markers.

PURPOSE: In this study, we tested the hypothesis that MIBI-positive and MIBI-negative adenomas of parathyroid glands (APGs) have distinct biochemical and histological markers that could help differentiate MIBI-positive from MIBI-negative APGs. PATIENTS AND METHODS: 40 patients with 41 APGs were included in the study. Patients were enrolled in the study after MIBI scintigraphy examinations had been carried out. Biochemical analyses included serum levels of calcium (Ca), intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D3 (25-OH-D3). All patients had neck ultrasound and MIBI examinations. After surgical resection the APGs were examined histologically. RESULTS: In each of 39 patients one APG could be confirmed by histology, and in one patient, two contralateral APGs were identified. MIBI studies were positive in 73 % and negative in 27 % of the APGs. False-positive cases were not observed. MIBI-negative APGs were only present in patients with iPTH values below 150 pg/ml. In 82 % of MIBI negative studies oxyphilic cells were absent, and this cell type was present in only 18 % of MIBI negative cases (p < 0.001). Regarding cysts within the APGs, no differences were demonstrated between MIBI positive or negative studies (p = 0.32). Fat cells were seen in none of the MIBI -negative studies and in only 3 % of MIBI positive studies (p = 0.08). CONCLUSIONS: For APGs, MIBI positivity correlates with serum iPTH concentration. The absence of oxyphilic cells with large numbers of mitochondria in APGs contributes to MIBI negativity, probably because of the reduced binding sites for the radiotracer.

[Implementation of a Vessel Sealing Device in a Centre for Thyroid Surgery: Risk and Economic Profit]. / Einführung der Gefäßversiegelung in einem Schilddrüsenzentrum: Risiken und wirtschaftlicher Nutzen.

BACKGROUND: This study investigated whether the use of the vessel sealing device LigaSure Small Jaw™ is cost-effective and safe in thyroid surgery despite the high cost of material. PATIENTS AND METHODS: We analysed the results of 224 thyroid operations performed by the same surgeon in three time intervals. We included thyroidectomies and bilateral near-total resections (including Dunhill surgery). Minimally-invasive resections (MIVAT), unilateral resections or subtotal resections (remains > 2 ml), patients with recurrent goiter, operations with neck dissections and sternotomies were excluded. In 72 procedures carried out during the first interval (1/2011 - 6/2011), the surgeon only used the clamp-and-tie technique. In the other two intervals (II: 7/2012 - 12/2012, n = 81 and III: 1/2014 - 6/2014: n = 71), the LigaSure Small Jaw was used. We investigated operation time (cut-seam time) and the complication rates between the groups (transient/permanent laryngeal nerve palsy, severe bleeding causing reoperation and hypocalcaemia, defined as Ca < 2.0 mmol/l). Differences were calculated with the t-test and the Wilcoxon rank test. Values are given as mean ± SEM. RESULTS: Specimen weight and the indication for surgery (nodular goiter or Basedow's disease) were comparable in all groups, but there were fewer thyroidectomies performed in the first interval (p = 0.009). There was no difference in complication rates between the groups, such as the rate of transient laryngeal nerve palsy in % (I: 2.17; II: 1.92; III 1.44) and postoperative hypocalcaemia in % (I: 20.8; II: 21.0; III 15.5). The use of the LigaSure Small Jaw in thyroidectomy procedures led to a significant reduction of operation time (II: Δ 27.4 min; III: Δ 25.6 min; p = 0.0001) compared to interval I. This was also found for bilateral near-total resections (II: Δ 24.3 min; III Δ 32.1 min; p = 0.0001). The InEK calculation for thyroidectomy procedures estimated personnel expenses in the OR to be about 1233 €. A 31-min reduction in operation time would save 440 € of personnel expenses. DISCUSSION: The use of the LigaSure Small Jaw during thyroid surgery is safe and cost-effective for thyroidectomy procedures and bilateral near-total resections.

Everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses.

BACKGROUND: Delayed wound healing is a serious side effect of mTOR inhibitor-based immunosuppression after solid organ transplantation. The aim of this study was to test the hypothesis that the mTOR inhibitor everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats received a colonic anastomosis. Then, animals were randomized to three groups of daily treatment with either vehicle or everolimus in two different dosages (1.0mg/kg or 3.0mg/kg). After 7 d, rats were sacrificed, and mechanical, histologic, and biochemical parameters of intestinal healing were assessed. RESULTS: Anastomotic bursting pressure was significantly decreased by everolimus in both dosages, whereas hydroxyproline content was reduced only by the high everolimus dosage. Everolimus diminished cellular proliferation and new vessel growth. Furthermore, both quantity as well as quality of newly synthesized collagen fibers in the anastomotic granulation tissue was reduced. On the other hand, myeloperoxidase-positive (MPO) cells and interleukin-6 (IL-6) concentrations were increased, as was the activity of matrix-metalloproteinases MMP-2 and MMP-9. CONCLUSION: Everolimus interferes with the inflammatory phase of healing. However, it remains unclear whether this phenomenon is involved in everolimus impairment of experimental anastomotic repair.

Predictive value of routine transcutaneous tissue oxygen tension (tcpO2) measurement for the risk of non-healing and amputation in diabetic foot ulcer patients with non-palpable pedal pulses.

BACKGROUND: It was evaluated whether transcutaneous tissue oxygen tension (tcpO2) measurement, when assessed in daily routine, can be used to predict the risk of non-healing and amputation in diabetic foot ulcer patients with non-palpable pedal pulses. MATERIAL/METHODS: Patients were followed up in an outpatient setting according to a comprehensive wound-care protocol. tcpO2 measurements were performed at the dorsum of the forefoot in a standardized setting. Patients were divided into three subgroups according to their initial tcpO2-readings (tcpO2 <20 mmHg, tcpO2 20-40 mmHg, tcpO2 >40 mmHg). Patients with clinical signs of soft tissue infection at the initial presentation were excluded. RESULTS: One hundred forty-one patients were enrolled. Wounds associated with a tcpO2 reading <20 mmHg demonstrated a significantly decreased probability of healing compared with those associated with a tcpO2 >40 mmHg (p=0.008). In addition, the risks of soft tissue infection (p=0.057) and hospitalization during follow-up (p=0.019) were different among the three groups. The overall amputation rate increased with decreasing tcpO2 (p=0.014) although there was no significant difference for major amputations (p=0.448). CONCLUSIONS: Routine assessment of tcpO2 is suitable as a clinical screening tool for estimating the risk of non-healing in diabetic foot ulcer patients without palpable pedal pulses. However, its predictive value for the risk of amputation remains unclear.

Effects of isoniazid and niacin on experimental wound-healing.

BACKGROUND: There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues. METHODS: One 8-mm, full-thickness wound was made in a standardized, ischemic skin flap and 1 in adjacent nonischemic skin on the back of male Sprague-Dawley rats. Starting just after wounding, twice-daily intraperitoneal isoniazid (10 mg/kg b.i.d.), xanthinol nicotinate (30 mg/kg), or saline (control) were given for 14 days. Wound-healing was monitored by planimetry and oxygen tension in periphery of the wound using a microcatheter probe. Cellular proliferation in granulation tissue was assessed by immunohistochemical detection of proliferating cell nuclear antigen. The angiogenic activity of isoniazid and niacin was assessed using in vitro and ex vivo models. RESULTS: Although wound ischemia was evident by decreased oxygen tension (26 +/- 10 mmHg; n = 9) compared with the adjacent nonischemic wounds (51 +/- 8 mmHg; n = 8), neither compound significantly influenced intracutaneous oxygen tension. Isoniazid (P < .0001), but not niacin, promoted ischemic wound-healing even though both compounds increased proliferation measured on day 14 (P < .01). In normal wounds, the cumulative change in relative wound area over 14 days was increased by niacin (P = .002), but not by isoniazid, although both niacin (P = .011) and isoniazid (P = .036) increased cellular proliferation. Neither isoniazid nor niacin showed activity in either an endothelial tube formation assay or organotypic angiogenic assay under normoxic conditions. CONCLUSION: Isoniazid was capable of stimulating wound-healing in ischemic tissue to the level of nonischemic wounds and might offer a novel treatment option for wounds associated with arterial insufficiency. Although active in normal wounds, niacin did not promote ischemic wound-healing.

M.A.I.D.: a prognostic score estimating probability of healing in chronic lower extremity wounds.

OBJECTIVE: To evaluate a wound-based prognostic score for chronic lower extremity wounds suitable for daily routine use capable of predicting long-term healing. SUMMARY BACKGROUND DATA: The main obstacle in the treatment of chronic wounds is to estimate long-term clinical outcome. For diabetic foot ulcers, several ulcer, and nonulcer-related risk factors associated with impaired healing have been described in the past. METHODS: A new chronic lower extremity ulcer score (M.A.I.D.) was created out of 4 clinically defined parameters, namely palpable pedal pulses (I), wound area (A), ulcer duration (D), and presence of multiple ulcerations (M). Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while wounds >4 cm were scored as 1 and wounds < or = 4 cm as 0. Ulcers lasting more than 130 days were categorized as 1 and wounds with a duration of <130 days as 0. Patients with multiple ulcerations were graded as 1 (=1) compared with those with single ulcers (=0). M.A.I.D. was calculated by adding these separate scores to a theoretical maximum of 4. RESULTS: Two thousand nineteen consecutive patients with 4004 wounds were included. When patients were divided into subgroups with the same M.A.I.D., we showed a decreasing probability of healing for ulcers with higher M.A.I.D. scores. An increase in the M.A.I.D. by 1 score-point reduced the chance for healing by 37%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the occurrence of soft-tissue infection during follow-up. CONCLUSIONS: This new chronic lower extremity ulcer score is capable of anticipating long-term probability of healing by combining 4 clinically assessable parameters. However, adequate and standardized wound care is an indispensable prerequisite for M.A.I.D. to be a valid diagnostic tool in daily clinical routine.

The impact of a micro-lightguide spectrophotometer on the intraoperative assessment of hepatic microcirculation: a pilot study.

INTRODUCTION: The intraoperative measurement of the peripheral microperfusion after liver transplantation is connected with quite an effort and a continuous evaluation in the postoperative follow up is not possible till now. PATIENTS AND METHODS: Before mobilization of the liver during surgical intervention the following parameters were measured on the surface of the right (segment 7/8) and the left (segment 2/3) liver lobe with a probe, combining laser-Doppler-flowmetry and tissue-spectrometry: the oxygen saturation (SO2), the relative capillary hemoglobin concentration (rHB), the blood flow (flow) and the blood flow velocity (velo). In addition the peripheral oxygen saturation (SPO2), the central venous pressure (ZVP), the positive endexspiratory pressure (PEEP) and the hemoglobin (HB) were documented. RESULTS: 9 patients (median age 75 years) were included in the study. SPO2, ZVP, PEEP and HB were regular. The parameters SO2, rHB, flow and velo showed no significant changes between the right and the left liver lobe. CONCLUSIONS: The O2C-method allows a reproducible intraoperative evaluation of the hepatic microcirculation.

Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized Wound Care Center.

With the dramatic increase in the aging population, the study and care of wounds in the elderly have become priority topics for both researchers and clinicians. The effects of aging on wound healing in humans have remained controversial. The study was a 5-year epidemiological evaluation of standardized data collected regularly during patients' visits at a specialized Wound Care Center with the aim to determine the key factors influencing the healing of chronic lower extremity wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure was statistically significantly lower in older patients compared with younger patients. The share of closed wounds decreased by nearly 25% in the elderly patients (>or=70 years). The relationship between the patient's age and the proportion of wound closure was nonlinear. The effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60. The chronicity of the wounds was illustrated by their recurrent nature, their long duration, the presence of multiple wounds, and the frequency of concurrent infection. Comorbidity was documented by the coprevalence of up to three underlying diseases related to impaired wound healing. The present study clearly showed that aging affects chronic wound healing negatively.

Fifty percent area reduction after 4 weeks of treatment is a reliable indicator for healing--analysis of a single-center cohort of 704 diabetic patients.

INTRODUCTION: The aim of the study was to investigate whether an area reduction greater than 50% within the first 4 weeks of treatment is associated with a higher long-term probability of healing. PATIENTS AND METHODS: We treated diabetic foot ulcers according to a comprehensive interdisciplinary wound care protocol. Follow-up was documented through a special wound documentation system. Data were entered into SPSS for statistical analysis to calculate the probability of healing according to the Kaplan-Meier method. Results were expressed as median (minimum-maximum), and the percentage of area reduction (PA) was defined as [(area(4 weeks)/area(baseline))x100)/area(baseline). Patients were divided into responders when PA reached at least 50% and nonresponders when PA was less than 50%. Healing was defined as PA=100%. RESULTS: In total, 704 patients were included into the analysis. Median time of follow-up was 71 (2-365) days. Wound duration was 31 (1-4018) days, and the initial wound size was calculated to be 1.18 (0.1-99) cm(2). In 27.8%, there was a positive probing to bone; in 64.5%, both pedal pulses were not palpable. Major amputation rate was 2.8% and minor amputation rate was 10.2%. The overall probability of healing was 35% after 12 weeks, 41% after 16 weeks, and 73% after 1 year. The surrogate visit (4 weeks) was performed after a median of 27 (14-42) days without a difference between responders and nonresponders. There were 334 (47%) responders and 370 (53%) nonresponders. Responders had a significantly higher probability of healing compared with nonresponders (12 weeks: 52.3% vs. 18.4%, P=.0001; 16 weeks: 46.7% vs. 26.5%, P=.0001; 1 year: 82.5% vs. 64.9%, P=.0001). CONCLUSIONS: The calculation of the percentage of area reduction after 4 weeks of treatment is a valid tool to estimate the probability of healing. In clinical practice, a reevaluation of the treatment schedule is recommended for wounds that do not reach 50% area reduction within the first 4 weeks of therapy.

Lactate modulates gene expression in human mesenchymal stem cells.

PURPOSE: Surgical wounds are characterised by elevated tissue lactate concentrations. This accumulated lactate is capable of stimulating collagen synthesis and new vessel growth as well. Recently, it has been shown in vivo that lactate is also able to favour homing of stem cells. The aim of this investigation was to test the hypothesis that lactate has an impact on gene expression of mesenchymal stem cells (MSC). MATERIALS AND METHODS: MSC were isolated from human bone marrow using the density gradient technique and incubated with alpha-methoxyethoxymethyl containing 10% fetal calf serum at 37 degrees C under 95% air and 5% CO(2). Cultured MSC were characterised by in vitro differentiation assays and fluorescence-activated cell sorting (FACS) analysis. Characterised MSC were treated with 15 mM lactate for different time periods (1, 6 and 24 h and 3 and 7 days). Gene expression analysis was performed using a custom-designed oligonucleotide microarray. A significant alteration of gene expression was defined as a two-fold stimulation or inhibition. The phenotype of MSC was investigated by FACS analysis of specific surface epitope patterns. RESULTS: Gene expression analysis shows 63 up- and 51 down-regulated genes after 1 h of treatment, 45 up- and 47 down-regulated genes after 6 h of treatment, 57 up- and 72 down-regulated genes after 24 h of treatment, 103 up- and 28 down-regulated genes after 3 days of treatment and 50 up- and 101 down-regulated genes after 7 days of treatment with lactate. The majority of the modulated genes are related to the expression of cytokines, transcription factors and cell-cycle- or cellular-matrix-associated proteins. In particular, lactate up-regulates the expression of interleukin-6 (3 days, 4.11-fold), of heat shock protein 70 (3 days, 2.36-fold) and of hypoxia-inducible factor-1alpha (3 days, 2.09-fold). A down-regulating effect of lactate is observed for superoxide dismutase 2 (1 h, 0.5-fold; 24 h, 0.4-fold; 7 days, 0.32-fold) and BCL2-associated X protein (24 h, 0.42-fold; 7 days, 0.4-fold). Expression of cell surface antigens clusters of differentiation 29, 44, 59, 73, 90, 105, 106 and 146 does not change over the time period of lactate treatment. CONCLUSIONS: Lactate modulates expression of genes involved in wound healing. However, lactate does not profoundly change the phenotype of MSC. In addition to providing new insights into the wound healing physiology, these data could also be the rationale for new treatment strategies for chronic non-healing wounds.

Self-expanding nitinol stents for treatment of infragenicular arteries following unsuccessful balloon angioplasty.

The feasibility of self-expanding nitinol stents for treatment of infragenicular arteries following unsuccessful balloon angioplasty was assessed. Options for lower limb percutaneous revascularization are limited, especially for complex vessel obstruction. Depending on the lesion and the experience of the interventionalist, the failure rate of balloon angioplasty (PTA) ranges between 10 and 40%. Until recently, no self-expanding stent for the use in the infragenicular arteries was available. This is the first report of the results for 18 consecutive patients who received 4F sheath compatible self-expanding nitinol stents following unsuccessful PTA or early restenosis. Twenty-four stents were implanted in 21 lesions for various indications residual stenosis >50% due to heavy calcification, flow-limiting dissection, occluding thrombus resistant to thrombolyis, thrombaspiration, and PTA, and early restenosis after previous PTA. Stent implantation was feasible in all cases. No complications occurred. After the stent implantation, all primarily unsuccessful interventions could be transformed into successful procedures with no residual stenosis >30% in any case. After 6 +/- 2 months, two of the 18 patients died, and 14 of the 16 remaining patients improved clinically. At follow-up, the patency could be assessed in 14 stented arteries. Three stents were occluded, one stent showed some neointimal hyperplasia (50-70% restenosis), the remaining ten stents showed no restenosis (0-30%). The use of self-expanding nitinol stents in tibioperoneal and popliteal arteries is a safe and feasible option for the treatment of unsuccessful PTA. The 6-months patency is high.

Stimulation of steroid-suppressed cutaneous healing by repeated topical application of IGF-I: different mechanisms of action based upon the mode of IGF-I delivery.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is accepted as a potent stimulus of wound healing when applied in combination with its binding proteins. However, there is only one study published that has investigated the effect of repeated topical application of unbound IGF-I on ischemic wound healing. The aim of this study was to show the effect of daily topical IGF-I therapy on cutaneous ulcer healing in a steroid-suppressed wound model. MATERIALS AND METHODS: Full-thickness wounds were created on the back of 40 male Sprague-Dawley rats. Before surgery, animals received depot-steroids subcutaneously. Wounds were treated daily with either a standard hydrogel dressing (control), topical IGF-I dissolved in 0.2% methylcellulose gel (IGF-I gel), or a hydrogel dressing containing IGF-I (IGF-I dressing). After 7 days of treatment, wounds were excised and measured by photoplanimetry. SMA- and PCNA-expression as well as the formation of granulation tissue were assessed in tissue sections. Results are given as median(min-max). Differences between groups were calculated by the Mann-Whitney U test. RESULTS: Subcutaneous injection of depot-steroids induced a significant delay in healing, as shown by an enlarged wound size [44(33-65) versus 25(20-35)] mm(2); P = 0.001). In steroid-treated rats, both IGF-I gel and IGF-I dressing enhanced excisional healing, as shown by a significant reduction in wound size (P = 0.0001), with IGF-I released from the dressing being even more effective than IGF-I gel (P = 0.03). However, in these animals only IGF-I released from the hydrogel dressing stimulated SMA- (P = 0.03) as well as PCNA-expression (P = 0.001) and increased granulation tissue formation (P = 0.018). CONCLUSIONS: Our data indicate that a repeated application of topical IGF-I enhances cutaneous ulcer healing. In addition, only the controlled release of IGF-I from the hydrogel dressing is capable of reversing the steroid-induced delay of healing, suggesting different mechanisms of action with respect to the mode of IGF-I delivery.