Echinococcus multilocularis specific antibody, systemic cytokine, and chemokine levels, as well as antigen-specific cellular responses in patients with progressive, stable, and cured alveolar echinococcosis: A 10-year follow-up.

BACKGROUND: The infestation with Echinococcus multilocularis larvae may persist in humans for up to decades without evident clinical symptoms. Longitudinal investigations are needed to understand the dynamic immunological processes in alveolar echinococcosis (AE) patients associated with an active and progressive, a stable or a regressive course of disease. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated the E. multilocularis specific antibody responses, systemic cytokine, and chemokine serum levels over a 10-year follow-up period, as well as cellular responsiveness in AE patients. Our results demonstrate a rapid decrease in antibodies against E. multilocularis specific antigen Em2+. Especially in cured patients, these antibodies remained negative, making them a significant predictor for cured AE. E. multilocularis specific IgG4, and indirect hemagglutination IHA decreased later in time, after around 5 years. While total IgE did not show significant dynamics over the course of disease, E. multilocularis specific IgE decreased after one to two years, and increasing levels were a significant predictor of progressive disease. There was no significant change in systemic IL-8, IL-9, CCL18 or CCL20 serum levels over time. Univariate analysis across groups indicated lower IL-8 levels in cured patients; however, this result could not be confirmed by multivariate analysis. Levels of CCL17 decreased during treatment, especially in cured patients, and thus might serve as a predictive or risk factor for progressive disease. Levels of IL-10 and CCL13 decreased during disease, especially after five and ten years of intervention. The E. multilocularis antigen (EmAg) inducible cellular productions of MCP1(CCL13), TARC(CCL17) and PARC(CCL18) were lowest in patients with cured AE and infection-free controls, while the EmAg inducible cellular production of IFN-γ increased after cure. Significant positive cytokine and chemokine correlations were observed in AE patients for IL-9, IL-10, CCL13(MCP-4), CCL17(TARC) and CCL20(LARC)(for all p<0.001). E. multilocularis specific IgG4 response correlated positively with TARC (p<0.001). Both markers enhanced over time in progressive disease and decreased after cure. The levels of IL-8, IL-10, MCP4 and LARC enhanced with AE regression. CONCLUSIONS/SIGNIFICANCE: Repeated biomarker surveys are advisable to evaluate progression or regression of disease during longitudinal follow-up and such analyses can support imaging techniques and improve staging of AE patients.

Analysis of vascularization in thyroid gland nodes with superb microvascular imaging (SMI) and CD34 expression histology: a pilot study.

BACKGROUND: The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation. METHODS: We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations. RESULTS: Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260). CONCLUSION: We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes.

Immunohistological detection of small particles of Echinococcus multilocularis and Echinococcus granulosus in lymph nodes is associated with enlarged lymph nodes in alveolar and cystic echinococcosis.

BACKGROUND: Alveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group. CONCLUSIONS/SIGNIFICANCE: mAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp.

Combining Computed Tomography and Histology Leads to an Evolutionary Concept of Hepatic Alveolar Echinococcosis.

Alveolar echinococcosis (AE) is caused by the intermediate stage of Echinococcus multilocularis. We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Echinococcus multilocularis Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of Echinococcus multilocularis (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.

Hepatic alveolar echinococcosis: correlation between computed tomography morphology and inflammatory activity in positron emission tomography.

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.

Symptoms of Primary Hyperparathyroidism in Men and Women: The Same but Different?

INTRODUCTION AND OBJECTIVE: Typical symptoms for primary hyperparathyroidism (pHPT) include osteoporosis, bone or joint pain, and nephrolithiasis, as well as fatigue, depression, gastritis, and cardiovascular disease. The female:male ratio was 3:1. The aim of this retrospective study was to evaluate the possible influence of gender-specific aspects of these symptoms. METHODS: From February 2018 to November 2019, parathyroid surgery was performed in 125 patients with pHPT (age: 23-83 years); 95 (76%) were female, and 30 (24%) were male. Preoperatively, a standardized medical history including 7 typical symptoms of pHPT was used for routine clinical documentation according to the StuDoQ Thyroid and Parathyroid Registry. RESULTS: For both groups (mean age: 60.4 years for females and 60.2 years for males), no sex differences were found in serum calcium or parathyroid hormone levels. For females, there was a tendency towards smaller hyperfunctioning parathyroid glands (16.8 vs. 20.5 mm) with less weight (1.14 vs. 1.52 g) and multiglandular disease. Nephrolithiasis was significantly more frequent in men than in women (36.7 vs. 16.8%, respectively; p = 0.036), but the difference in hypertension was not significant (60% in men vs. 47.4% in women, p = 0.230). Women reported significantly more often bone and joint pain (44.2% in women vs. 20% in men, p = 0.053) and depressive episodes (32.6% in women vs. 10% in men, p = 0.016). CONCLUSION: 91.2% of patients transferred for parathyroidectomy described typical symptoms of pHPT. However, an unexpected high gender difference was found following the analysis of symptoms documented in the StuDoQ Registry.

Simple liver cysts and cystoid lesions in hepatic alveolar echinococcosis: a retrospective cohort study with Hounsfield analysis.

BACKGROUND: Alveolar echinococcosis (AE) is a rare zoonosis caused by the larval stage of the tapeworm Echinococcus multilocularis. AE lesions affect the liver in more than 98% of cases. AE lesions have various morphological characteristics that are described in the Echinococcus multilocularis Ulm classification for computed tomography (EMUC-CT). One of these characteristics is a cystoid portion. The aim of the study was to compare the density of simple hepatic cysts with cystoid portions of AE lesions classified on the basis of the EMUC-CT. RESULTS: Hounsfield Unit (HU) measurements of the cystoid portions of all EMUC-CT type I-IV AE lesions (n = 155) gave a mean of 21.8 ± 17.6, which was significantly different from that of 2.9 ± 4.5 for the simple hepatic cysts (p < 0.0001). The difference between each of the individual AE types and simple hepatic cysts was also significant. In addition, the HU values of the cystoid portions in types I, II and IIIa/b and simple cysts were each significantly different from type IV (p < 0.0001). The HU measurements in type IV presented by far the highest mean. CONCLUSIONS: The significantly higher density measured in the cystoid portions of hepatic AE lesions offers a good means of differentiation from simple hepatic cysts.

Calcitonin concentrations in patients with chronic kidney disease on hemodialysis in reference to parathyroidectomy.

OBJECTIVE: Calcitonin is considered to be a biomarker of medullary thyroid carcinoma and C-cell hyperplasia, but calcitonin can also be elevated in about 30% of the patients with end-stage kidney disease. We reported preoperative calcitonin serum levels in 31 patients on hemodialysis before parathyroid surgery, evaluate influencing factors on calcitonin levels and determine postoperative calcitonin levels after parathyroid surgery. RESULTS: Median preoperative serum calcitonin was 8 pg/ml (range 2 to 165 pg/ml), serum calcitonin concentration declined postoperatively to 3 pg/ml (range 1 to 192 pg/ml). There was a strong positive correlation between pre- and postoperative serum calcitonin levels (r = 0.92; p > 0.01). Elevated preoperative serum calcitonin concentrations (more than 10 pg/ml) were found in 14 out of 32 dialysis-dependent patients (44%). Preoperative calcitonin levels of male patients were significantly higher than female patients. Hypercalcitoninemia showed a positive correlation to body mass index (p < 0.01). We found no correlation between preoperative calcitonin levels and patients' age, duration of hemodialysis dependency, cinacalcet medication or preoperative concentrations of parathyroid hormone, creatinine and calcium. Basal calcitonin levels higher than 10 pg/ml are common in patients on dialysis. Male gender and morbid obesity are risk factors for hypercalcitoninemia. Calcitonin concentration decreases after parathyroid operation.

Can Met-PET/CT Predict Sporadic Multiglandular Hyperparathyroidism? Report of a Case and Review of the Literature.

BACKGROUND: Primary hyperparathyroidism (pHPT) is a common endocrine disorder of the parathyroid glands. In most cases pHPT is caused by single gland disease, but about 10% of patients suffer from sporadic multiglandular disease (MGD). Patients with MGD, especially with ectopic parathyroid adenomas, have an increased risk for persistence/recurrence after surgery. Normally, sporadic MGD cannot be diagnosed preoperatively by parathyroid scintigraphy. We analyzed the potential of positron emission tomography/computed tomography (Met-PET/CT) to predict MGD. METHODS AND CASE PRESENTATION: We reviewed the literature, if preoperative Met-PET/CT could predict MGD in patients with pHPT. Further, we present a 71-year-old female with ectopic MGD. Preoperative localization via Met-PET/CT showed MGD with two areas suspected to be enlarged parathyroid glands (left lateral to the thyroid lobe and posterior mediastinum). Both diagnostic findings were extirpated and parathormone dropped into normal levels. RESULTS: We identified four additional manuscripts, referring to MGD and Met-PET/CT with divergent results. Preoperative localization diagnostics using Met-PET/CT may not necessarily identify MGD. In most cases, Met-PET/CT localized only one adenoma and localizes larger adenomas more reliably than smaller adenomas. CONCLUSION: Identifying patients at risk of MGD preoperatively remains challenging. We found MET-PET/CT seems to predict MGD in patients with large size and high weight PTH adenomas. For ectopic parathyroid adenomas, accurate preoperative localization is the key to successful surgical removal. Met-PET/CT appears to have great potential in soft-tissue analysis of complex anatomical regions and can predict ectopic parathyroid adenomas.

TRAILblazing Strategies for Cancer Treatment.

In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) inducing the formation of a death-inducing signalling complex (DISC) thereby activating the apoptotic cascade. The ability of TRAIL to also induce apoptosis independently of p53 makes TRAIL a promising anticancer agent, especially in p53-mutated tumour entities. Thus, several so-called TRAIL receptor agonists (TRAs) were developed. Unfortunately, clinical testing of these TRAs did not reveal any significant anticancer activity, presumably due to inherent or acquired TRAIL resistance of most primary tumour cells. Since the potential power of TRAIL-based therapies still lies in TRAIL's explicit cancer cell-selectivity, a desirable approach going forward for TRAIL-based cancer therapy is the identification of substances that sensitise tumour cells for TRAIL-induced apoptosis while sparing normal cells. Numerous of such TRAIL-sensitising strategies have been identified within the last decades. However, many of these approaches have not been verified in animal models, and therefore potential toxicity of these approaches has not been taken into consideration. Here, we critically summarise and discuss the status quo of TRAIL signalling in cancer cells and strategies to force tumour cells into undergoing apoptosis triggered by TRAIL as a cancer therapeutic approach. Moreover, we provide an overview and outlook on innovative and promising future TRAIL-based therapeutic strategies.

Postoperative swallowing disorder after thyroid and parathyroid resection.

INTRODUCTION: Dysphagia is frequently reported after thyroidectomy. Here, we investigated the incidence of postoperative dysphagia after uncomplicated thyroidectomy and parathyroidectomy. Further, we analyzed diagnosis and types of therapy to identify possible patients at risk. PATIENTS AND METHODS: A questionnaire was sent to 372 consecutive patients whose thyroid or parathyroid glands were operated on between May 2013 and October 2014 at Ulm University Hospital. Patients were questioned at least 6 months postoperatively. RESULTS: In the evaluation, 219 questionnaires could be included. Fifty-three (21.3%) patients reported that the overall postoperative swallowing process was better or more trouble-free. In 110 (50.2%) patients, dysphagia was reported only immediately postoperative and disappeared later spontaneously. Sixteen patients (7.3%) stated that after a maximum of 3 months after surgery they suffered from dysphagia. One (0.5%) patient stated that up to 3 months postoperatively, swallowing problems had been successfully treated by logopedic therapy. In 39 (17.6%) patients, the complaints persisted for more than 3 months or still existed at the time of the interview. We found no correlation between dysphagia and patients' age or gender, the specimen volume, and patients' body mass index. The more invasive the operation was, the more patients suffered from dysphagia. Analyzing the frequency of dysphagia according to different diagnoses, we found a significant risk of postoperative dysphagia in patients with Graves' disease and carcinoma. Patients operated on for hyperparathyroidism were at significantly decreased risk of dysphagia. CONCLUSION: Nearly 20% of patients reported postoperative dysphagia after uncomplicated thyroidectomy and parathyroidectomy, especially after major surgical intervention. We found a significant risk of postoperative dysphagia in patients with Graves' disease and carcinoma and a decreased risk for patients operated on for hyperparathyroidism.

Value of Ultrasonography in the Diagnosis of Inguinal Hernia - A Retrospective Study.

PURPOSE: The diagnosis of an inguinal hernia is usually made clinically. Precise imaging appears to be necessary when the clinical examination is inconclusive. The aim of this study was to determine the diagnostic value of ultrasonography for inguinal hernias and whether it influences the decision for or against surgery. MATERIALS AND METHODS: This study was a single-center retrospective study carried out from January 2012 to December 2016. All 326 patients had undergone ultrasound scanning of the groin as part of the diagnostic workup. Besides surgical findings being the gold standard, follow-up data and alternative ultrasound diagnoses were considered as references, allowing us to assess the accuracy of negative ultrasound findings as well. RESULTS: The findings on ultrasonography were positive in 248 patients and negative in 78 patients. In addition to 201 operated patients, we were able to validate a further 40 patients by means of a questionnaire and the alternative ultrasound diagnoses. The correlation with all three references resulted in a sensitivity of 97 %, a specificity of 77 %, a positive predictive value of 95 %, and a negative predictive value of 87 %. CONCLUSION: Ultrasonography is an accurate method for evaluating inguinal hernias. High sensitivity makes it particularly suitable for ruling out an inguinal hernia when the findings are negative. An ultrasound scan carried out in addition to clinical examination can therefore help to determine the right indication for surgical intervention.

The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma.

The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC's resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

Impact of affected lymph nodes on long-term outcome after surgical therapy of alveolar echinococcosis.

PURPOSE: Alveolar echinococcosis (AE) is a life-threatening helminthic disease. In humans, AE mostly affects the liver; the regional hepatic lymph nodes may be involved, indicating dissemination of AE from the liver. To achieve complete removal of the disease, enlarged hepatic lymph nodes may be resected during surgical treatment. We evaluated the frequency of affected lymph nodes by conventional microscopic and immunohistochemical analyses including detection of small particles of Echinococcus multilocularis (spem). Furthermore, we analyzed the association of resection of enlarged and affected lymph nodes with long-term outcome after surgical therapy of patients who underwent surgery with curative intent. MATERIALS AND METHODS: We identified 43 patients who underwent hepatic surgery with curative intent with lymph node resection for AE. We analyzed the cohort for the manifestation of the parasite in the resected lymph nodes by conventional histology and by immunohistochemistry and compared these data with the further course of AE. RESULTS: Microscopically infected lymph nodes (laminar layer visible) were found in 7 out of these 43 patients (16%). In more than three quarters (25/32) of all specimens investigated, lymph nodes showed spems when stained with antibody against Em2G11, a monoclonal antibody specific for the Em2 antigen of the Echinococcus multilocularis metacestode. Most frequently, lymph nodes were resected due to enlargement. The median size of microscopically affected lymph nodes was 2 cm (range, 1.2 to 2.5 cm), the median size of immunohistochemically and non-affected lymph nodes was 1.3 cm each (range, "small" to 2.3 or 2.5 cm, respectively). Median follow-up was 8 years for all patients, 5 years for patients with lymph node resection, and 4 years for patients with infested lymph nodes. Overall, recurrent disease was seen in ten patients (10/109; 9%) after a median period of 1.5 years (range, 4 months to 4 years). None of the seven patients with conventionally microscopically affected lymph nodes suffered from recurrent disease. One patient with negative resected nodes and one patient with spems showed recurrent disease after 4 and 35 months, respectively. CONCLUSIONS: Lymph node involvement in AE is frequent, particularly when evaluated by immunohistochemical examination of lymph nodes with the monoclonal antibody Em2G11. Affected lymph nodes tend to be larger in size. Lymph node involvement is not associated with recurrent disease and therefore warrants further analysis of the biological significance of lymph node involvement.

Should We Keep Walking along the Trail for Pancreatic Cancer Treatment? Revisiting TNF-Related Apoptosis-Inducing Ligand for Anticancer Therapy.

Despite recent advances in oncology, diagnosis, and therapy, treatment of pancreatic ductal adenocarcinoma (PDAC) is still exceedingly challenging. PDAC remains the fourth leading cause of cancer-related deaths worldwide. Poor prognosis is due to the aggressive growth behavior with early invasion and distant metastasis, chemoresistance, and a current lack of adequate screening methods for early detection. Consequently, novel therapeutic approaches are urgently needed. Many hopes for cancer treatment have been placed in the death ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) since it was reported to induce apoptosis selectively in tumor cells in vitro and in vivo. TRAIL triggers apoptosis through binding of the trans-membrane death receptors TRAIL receptor 1 (TRAIL-R1) also death receptor 4 (DR4) and TRAIL receptor 2 (TRAIL-R2) also death receptor 5 (DR5) thereby inducing the formation of the death-inducing signaling complex (DISC) and activation of the apoptotic cascade. Unlike chemotherapeutics, TRAIL was shown to be able to induce apoptosis in a p53-independent manner, making TRAIL a promising anticancer approach for p53-mutated tumors. These cancer-selective traits of TRAIL led to the development of TRAIL-R agonists, categorized into either recombinant variants of TRAIL or agonistic antibodies against TRAIL-R1 or TRAIL-R2. However, clinical trials making use of these agonists in various tumor entities including pancreatic cancer were disappointing so far. This is thought to be caused by TRAIL resistance of numerous primary tumor cells, an insufficient agonistic activity of the drug candidates tested, and a lack of suitable biomarkers for patient stratification. Nevertheless, recently gained knowledge on the biology of the TRAIL-TRAIL-R system might now provide the chance to overcome intrinsic or acquired resistance against TRAIL and TRAIL-R agonists. In this review, we summarize the status quo of clinical studies involving TRAIL-R agonists for the treatment of pancreatic cancer and critically discuss the suitability of utilizing the TRAIL-TRAIL-R system for successful treatment.

CK1α overexpression correlates with poor survival in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the fourth leading cause of cancer related deaths worldwide and prognosis in advanced tumor stage still remains poor. Since CK1 isoforms have been reported to be deregulated in several tumor entities CK1 has emerged as a novel drug target in cancer therapy. In this study we set out to investigate whether CK1α might have the potential to serve as prognostic marker. METHODS: CK1α RNA and protein expression levels in healthy and tumor tissue of CRC patients were analyzed using quantitative real-time PCR and Western Blot analysis, respectively. Prognostic relevance was investigated by correlating obtained CK1α expression levels with patients' survival rate generating Kaplan-Meier survival plots. RESULTS: It could be shown that CK1α is overexpressed in colorectal tumor tissue compared to normal tissue and CK1α overexpression in tumor tissue correlates with poor survival in CRC patients. Results become more significant when only considering patients with high-grade tumors, as well as patients assigned to UICC II and UICC III stage. Furthermore, Cox regression analysis revealed that CK1α is an independent prognostic factor. In addition, tumors expressing decreased levels of the kinase reveal positive effects on overall survival when localized in the right colon compared to those in the left side. CONCLUSION: In summary, this study provides evidence for the first time that CK1α RNA levels might serve as prognostic marker for CRC.

Thyroid gland hemorrhage after blunt neck trauma: case report and review of the literature.

BACKGROUND: Thyroid hemorrhage is considered to be an uncommon complication following blunt trauma to the neck. This condition is potentially life-threatening due to airway compression and may therefore require emergency airway management and surgical intervention in some cases. CASE PRESENTATION: We present the case of a 52-year-old woman who experienced a traumatic thyroid gland rupture (right lobe) with subsequent active arterial bleeding from branches of the inferior thyroid artery. On the same day, the patient presented to our emergency department with a painful swelling of the neck with an inspiratory stridor and hoarseness a few hours after a cycling accident. A right hemithyroidectomy was performed. The postoperative course was uneventful. We identified 33 additional cases published in English literature within the last 30 years, reporting blunt trauma to the neck with hemorrhagic complication of the thyroid gland. We provide a systematic review and particularly consider the aspects of endocrine surgery. CONCLUSION: The treatment approach for patients with blunt thyroid trauma should be dependent on the extent of the thyroid injury. Patients with tracheal compression, active bleeding and increasing hoarseness/shortness of breath require emergency airway control and often surgical exploration for hemorrhage control followed by resection of the ruptured thyroid. Importantly, in contrast to routine thyroid surgery, no electromyographic endotracheal tube is used during emergency intubation. Exchange of an endotracheal tube should be carefully evaluated due to difficult airway management in this setting. For protection against double-sided recurrent nerve palsy and postoperative hypoparathyroidism, a unilateral approach is preferable whenever possible.

Albendazole increases the inflammatory response and the amount of Em2-positive small particles of Echinococcus multilocularis (spems) in human hepatic alveolar echinococcosis lesions.

BACKGROUND: Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy. A broad panel of monoclonal antibodies was used to characterize the lesion by immunohistochemistry. A change in the cellular infiltrate was observed between the different chemotherapy times. During the initial phases of treatment an increase in CD15+ granulocytes and CD68+ histocytes as well as in small particles of Echinococcus multilocularis (spems) was observed in the tissue surrounding the metacestode. Furthermore, we observed an increase in CD4+ T cells, CD20+ B cells and CD38+ plasma cells during a longer duration of treatment. CONCLUSIONS/SIGNIFICANCE: ABZ treatment of AE leads to morphological changes characterized by an initial, predominantly acute, inflammatory response which is gradually replaced by a response of the adaptive immune system.

Comprehensive diagnosis and treatment of alveolar echinococcosis: A single-center, long-term observational study of 312 patients in Germany.

Alveolar echinococcosis (AE) is the most Iethal human helminthic infection. The malignancy-like disease is rare, but morbidity and treatment costs are high. Objective of the study was to identify factors at baseline and during specific AE therapy influencing the long-term outcome of the disease. All patients with AE seen at the specialized treatment unit in Ulm between January 1992 and December 2011 were included in the analysis. The data of 312 patients were analyzed; 108 were diagnosed before 2000 (series A), 204 since 2000 (series B); 290 received specific AE treatment. Patients of series B were more often symptom-free at diagnosis (44.1% vs. 21.3%), had lower disease stages (50.0% vs. 34.2%) and more complete resections (57.7% vs. 20.0%), but higher rates of side effects and drug toxicity (54.1% vs. 40.8%). In series B, more patients remained relapse- or progression-free after 5 years (90.5% vs. 82.8%); after 10 years, the ratio of relapses converged (70.3% vs. 66.9%, p=0.0507). Relapses or progression occurred more often after incomplete surgery or long treatment pauses. The 5-year and 10-year survival rates were 96.9% and 90.6%, respectively, and 17% of the patients were cured. We observed a shift towards early diagnosis, earlier initiation of specific therapy and more complete resections after 2000. Although diagnosis and treatment of AE pose a challenge, with an individual interdisciplinary management 88.8% of the patients have a favorable outcome.