Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Adrenal lesion classification with abdomen caps and the effect of ROI size.

Accurate classification of adrenal lesions on magnetic resonance (MR) images are very important for diagnosis and treatment planning. The detection and classification of lesions in medical imaging heavily rely on several key factors, including the specialist's level of experience, work intensity, and fatigue of the clinician. These factors are critical determinants of the accuracy and effectiveness of the diagnostic process, which in turn has a direct impact on patient health outcomes. With the spread of artificial intelligence, the use of computer-aided diagnosis (CAD) systems in disease diagnosis has also increased. In this study, adrenal lesion classification was performed using deep learning on MR images. The data set used was obtained from the Department of Radiology, Faculty of Medicine, Selcuk University, and all adrenal lesions were identified and reviewed in consensus by two radiologists experienced with abdominal MR. Studies were carried out on two different data sets created by T1- and T2-weighted MR images. The data set consisted of 112 benign and 10 malignant lesions for each mode. Experiments were performed with regions of interest (ROIs) of different sizes to increase the working performance. Thus, the effect of the selected ROI size on the classification performance was assessed. In addition, instead of the convolutional neural network (CNN) models used in deep learning, a unique classification model structure called Abdomen Caps was proposed. When the data sets used in classification studies are manually separated for training, validation, and testing, different results are obtained with different data sets for each stage. To eliminate this imbalance, tenfold cross-validation was used in this study. The best results obtained were 0.982, 0.999, 0.969, 0.983, 0.998, and 0.964 for accuracy, precision, recall, F1-score, area under the curve (AUC) score, and kappa score, respectively.

The role of oxidant status on the etiopathogenesis of unexplained infertility and intracytoplasmic sperm injection - embryo transfer success: a case-control study.

The present study aims to evaluate the role of follicular fluid (FF) and serum (s) total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) on the etiopathogenesis of unexplained infertility (UI) and intracytoplasmic sperm injection-embryo transfer (ICSI-ET) success. Twenty UI patients and 20 controls with male factor undergoing an ICSI-ET cycle were recruited. FF samples aspirated from mature follicles and blood samples collected just before the oocyte retrieval were stored until analysis. Embriyo quality and implantation, clinical pregnancy and living birth rates were evaluated.FF-TOS and FF-OSI of the UI patients were higher than the control group. s-TOS and s-OSI were significantly increased in the UI group compared to the control group. However, only s-TOS was positively associated with UI diagnosis after age-adjustment. FF-OSI was negatively associated with embryo quality in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI on implantation, clinical pregnancy and live birth rate was observed. In conclusion, especially s-TOS can have a partial role in the etiopathogenesis of UI. High FF-OSI can decrease the quality of embryo in patients with UI.Impact statementWhat is already known? Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), which is the ratio of TOS to TAS, provide a broad overview of redox status.What do the results of this study add? An elevated serum TOS (s-TOS) was associated with UI after age-adjustment. Follicular fluid OSI (FF-OSI) was negatively associated with embryo quality and embryo score in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI was observed on implantation, clinical pregnancy, and live birth rate.What are the implications of these findings for clinical practice and/or further research? Evaluation of FF-OSI in women with unexplained infertility can be considered to predict embryo quality. Further studies that evaluate antioxidant agents to decrease oxidative stress in UI and its' clinical implications are warranted.

Tailored total neoadjuvant therapy for locally advanced rectal cancer: One size may not fit for all!

While current neoadjuvant protocols have proven benefits on local control for majority of patients with locally advanced rectal cancer, there are certain clinical conditions that require future advances for improving the outcomes. Total neoadjuvant therapy incorporates systemic chemotherapy planned within standard neoadjuvant protocols either before or after radiotherapy for locally advanced rectal cancer as a whole. Enhanced compliance with planned oncological therapy, tumour downstaging, administration of chemotherapy at the earliest time in the disease course to help assessing chemosensitivity are the proposed benefits of total neoadjuvant therapy in patients with locally advanced rectal cancer. Patient selection criteria for administration of total neoadjuvant therapy in the recent guidelines are unclear. Since current literature is inconclusive for the optimal sequence and type of radiotherapy and chemotherapy, premature incorporation of total neoadjuvant therapy for all locally advanced rectal cancers may result in overtreatment and subsequently toxicity. This article aims to discuss the current literature and to propose a future perspective by considering real-life scenarios reflecting patients' needs for treatment of locally advanced rectal cancer.

Comparison of Serum VEGF, IGF-1, and HIF-1α Levels in Children with Autism Spectrum Disorder and Healthy Controls.

The aim of this study was to determine whether serum VEGF, IGF-1, and HIF-1α levels differed between Autism Spectrum Disorder (ASD) patients and healthy controls. A total of 40 children with ASD and 40 healthy controls aged 4-12 years were included. Serum levels of VEGF, IGF-1, and HIF-1α were measured using commercial enzyme-linked immunosorbent assay kits. Serum IGF-1 levels were found to be statistically significantly higher in the ASD group than in the control group. Serum HIF-1α levels were borderline significantly lower in the ASD group. There was no statistically significant difference in serum VEGF levels between the two groups. IGF-1 and HIF-1α may play a potential role in the etiopathogenesis of ASD.

Serum zonulin and claudin-5 levels in patients with schizophrenia.

The aim of this research was to assess whether or not changes in the concentrations of serum zonulin and claudin-5 in patients with schizophrenia could have etiopathogenetic importance. In previous studies, the data regarding the relationship between intestinal and blood-brain barrier (BBB) permeability and the etiology of schizophrenia have been limited. In this study, we assumed that there may be a difference in serum zonulin and claudin-5 levels in patients with schizophrenia, which may affect the severity of the disease. Fifty schizophrenia patients and 50 healthy controls were included in this study. The patients were administered the Positive Symptoms Assessment Scale (SAPS) and Negative Symptoms Assessment Scale (SANS) to determine the severity of symptoms. Venous blood samples were collected, and the serum zonulin and claudin-5 levels were measured. The mean serum zonulin levels were significantly increased in patients with schizophrenia when compared to the control group. Serum claudin-5 levels were decreased in the schizophrenia patients when compared to the controls. The present study indicates that zonulin is increased and claudin-5 is decreased in patients with schizophrenia. These findings extend the existing knowledge on the dysregulation of intestinal permeability, especially zonulin, and BBB, especially claudin-5, and show that both proteins may be involved in the etiopathogenesis of schizophrenia.

Clinical use of copeptin in migraine patients admitted to the emergency department.

PURPOSE: The purpose of this study was to investigate the clinical use of copeptin to evaluate migraine attacks in the Emergency Department. An additional aim was to detect changes in serum copeptin levels in migraine patients during attack and attack-free periods. METHODS: This prospective case-control study included 52 migraine patients and 51 healthy individuals with similar demographic characteristics. Blood samples were collected from migraine patients both in attack and attack-free periods. RESULTS: The mean copeptin levels in the patients group in the attack and attack-free periods were 689.28 and 576.68 pg/ml, respectively, whereas they were 608.68 pg/ml in the control group. There was a significant difference in the mean copeptin level in the attack period and attack-free periods (p = 0.026). The sensitivity and specificity of copeptin in detecting headache episodes in migraine patients were 58.8% and 60.7%, respectively, at a cut-off value of 388.67 pg/ml. CONCLUSION: This is the first study to investigate the diagnostic efficacy of serum copeptin levels in migraine patients. Although the diagnostic efficacy of serum copeptin levels for migraines was unsatisfactory, it could be helpful at management of migraine patients in ED.

Jaw and Teeth Segmentation on the Panoramic X-Ray Images for Dental Human Identification.

Due to the damage to biometric properties in the event of natural disasters, like fire or earthquakes, it is very difficult to identify human remains. As teeth are more durable than other biometric properties, identifying information obtained from them is much more reliable. Therefore, in cases where alternative biometric properties cannot be obtained or used, information taken from teeth may be used to identify a person's remains. In recent years, many studies have shown how the identification process, previously performed manually by a forensic dental specialist, can be made faster and more reliable with the assistance of computers and technology. In these studies, the x-ray image is subdivided into meaningful parts, including jaws and teeth, and dental properties are extracted and matched. In order to extract the features accurately and ensure better matching, it is important to segment images properly. In this study, (i) lower and upper jaw and (ii) tooth separation was performed to segment panoramic dental x-ray images to assist in identifying human remains. To separate the jaws, a novel meta-heuristic optimization-based model is proposed. To separate teeth, a user-assisted, semi-automatic approach is presented. The proposed methods have been performed with a computer program. The results of the implementation of these methods of jaw and tooth separation in panoramic tooth images are encouraging.

Serum zonulin and claudin-5 levels in patients with bipolar disorder.

BACKGROUND: The etiology in bipolar disorder has not been fully understanding. There are limited data regarding the relationship between the permeability of intestinal and blood-brain barrier (BBB), and bipolar disorder etiology. Zonulin is regarded as a non-invasive biomarker for intestinal permeability. Claudin-5 is an important part of BBB permeability. In this study, we assumed that there may be a deterioration in serum zonulin and claudin-5 levels in patients with bipolar disorder and this may affect the severity of the disease. METHODS: Forty-one bipolar disorder patients (21 patients in remission and 20 patients with manic episodes) and 41 healthy controls were included in this study. The patients were administered Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) to determine the severity of manic and depressive symptoms, respectively. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured. RESULTS: The mean serum zonulin and claudin-5 levels in patients were significantly higher than healthy controls. There is no difference zonulin and claudin-5 levels between patients with manic episodes and patients in remission. LIMITATION: This study's small sample size limits the generalization of these outcomes to a larger population. Also, a major limitation of our study is lack of evaluations of gut microbiota in patients with bipolar disorder and controls. CONCLUSION: In conclusion, the current research indicates that zonulin and claudin-5 are increased in patients with bipolar disorder and this finding may contribute to the role of intestinal permeability or BBB in the pathogenesis of bipolar disorder.

The role of chemotherapy in unresectable or metastatic adenocarcinoma of the stomach and gastroesophageal junction.

Gastric cancer including gastroesophageal junction adenocarcinomas are most challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly diagnosed patients will have disseminated disease and in need of systemic therapy. Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with differences in geographical distribution, histopathology, and molecular subtypes. Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory irinotecan are active drugs against AGC. The combination of fluoropyrimidines with a platinum compound is the optimal first-line treatment. Trastuzumab (given in combination with chemotherapy for HER2 positive tumors) and ramucirumab are the only targeted agents approved by the food and drug administration for the treatment in AGC for first and second line respectively. Efforts are being directed to harness the immune system with checkpoint inhibitors and to combining these drugs with chemotherapy in clinical trials. Genomic technology advancements might provide us with the tools to create personalized treatment for AGC in the near future with the goal to improve outcomes. In this article we aimed to review current therapeutic regimens for AGC with an update of ongoing clinical trials.

Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer.

Although involvement of pancreas is a common finding in small cell lung cancer (SCLC), metastasis-induced acute pancreatitis (MIAP) is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status.

Predictive and prognostic significance of p27, Akt, PTEN and PI3K expression in HER2-positive metastatic breast cancer.

BACKGROUND: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. MATERIALS AND METHODS: Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. RESULTS: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). CONCLUSIONS: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Locally metastatic mucinous rectal adenocarcinoma: Imaging diagnosis with DW-MRI in comparison with PET-CT.

A 56-year-old male patient with locally advanced mucinous rectal cancer underwent neoadjuvant chemoradiotherapy. Follow-up imaging with positron emission tomography-computed tomography (PET-CT) revealed a local response to chemoradiotherapy, whereas diffusion-weighted magnetic resonance imaging (DW-MRI) showed newly presented sacral bone metastasis. Histopathologically confirmed bone metastasis and the local tumor were surgically removed. Repeat DW-MRI revealed tumor recurrence in the sacral excision zone eight months after surgery, which was reconfirmed by histopathology. This case shows the superior imaging ability of DW-MRI in the diagnosis of mucinous tumors in comparison to PET-CT.

Fulminant abdominal gas gangrene in metastatic colon cancer.

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms.

Pleomorphic carcinoma of the lung with high serum beta-human chorionic gonadotropin level and gynecomastia.

Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (ßhCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. ßhCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for ßhCG. Serum ßhCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, ßhCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. ßhCG expression may be associated with aggressive clinical course and increased risk of recurrence, also ßhCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma.

Morphometric analysis of metacarpophalangeal and proximal interphalangeal palmar plates.

Palmar plates are being used as a source of graft in radial or ulnar collateral ligament reconstruction, pulley reconstruction, and volar plate arthroplasty. The purpose of this study is to determine morphometric and major histological differences of palmar plates in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints among fingers, and supply sufficient data which would be useful in reconstruction procedures. Ninety-six MCP and 96 PIP palmar plates of 12 well-preserved formalin-fixed cadavers were measured focusing on their length, width, central thickness, and lateral thickness and statistically analyzed using ANOVA. Randomized three male and three female cadavers' specimens were examined histologically after staining with Masson's trichrome. For central thickness of the PIP joint level, there was significant difference among fingers, caused by the middle and little fingers. For lateral thickness of the PIP joint level, there was significant difference which was originated from little fingers. MCP palmar plates were significantly thicker than PIP joint levels for most of the fingers. There were thicker and denser collagen bands in MCP than PIP palmar plates. The relation of size-related parameters was not close with the thickness parameters. The predicted sizes and thicknesses of palmar plates vary according to fingers. The data collected for each finger in this study should be used as a guide in reconstructive procedures that use palmar plates as source of graft.