Primary Liver Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review.

A primary liver perivascular epithelioid cell tumor (PEComa) is an extremely rare entity. In this article, we present a case report with a review of the literature on the patients diagnosed with primary liver PEComa and an elaboration of diagnostic and treatment modalities. A systematic literature search was conducted using the terms "perivascular epithelioid cell tumor", "PEComa", "liver", and "hepatic". All articles describing patients diagnosed with primary liver PEComa were included. We identified a total of 224 patients of primary liver PEComa from 75 articles and a case from the present study with a significant preponderance of females (ratio 4:1) and with a mean age of 45.3 ± 12.1 years. Most of the patients (114 out of 224, 50.9%) were asymptomatic. A total of 183 (81.3%) patients underwent surgical hepatic resection at the time of diagnosis, while 19 (8.4%) underwent surveillance. Recurrence and metastases were detected in seven (3.1%) and six (2.7%) patients, respectively. In conclusion, surgical resection remains the cornerstone of therapy; however, the presence of nonspecific imaging features makes it difficult to reach a definite diagnosis preoperatively. Therefore, a multidisciplinary approach should be the gold standard in selecting the treatment modality.

The Impact of Chemotherapy and Transforming Growth Factor-ß1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients.

An ongoing debate surrounds the impact of chemotherapy on post-hepatectomy liver regeneration in patients with colorectal cancer liver metastases (CRLM), with unclear regulatory mechanisms. This study sought to delve into liver regeneration post-resection in CRLM patients, specifically examining the roles of hepatocyte growth factor (HGF) and transforming growth factor ß1 (TGF-ß1). In this longitudinal observational study, 17 patients undergoing major liver resection for CRLM and 17 with benign indications as controls were enrolled. Liver regeneration within 30 postoperative days was assessed via CT, considering clinicopathological characteristics, liver enzymes, liver stiffness by elastography, and the impact of HGF and TGF-ß1 on liver regeneration. The results revealed that the control group exhibited significantly higher mean liver regeneration volume (200 ± 180 mL) within 30 days postoperatively compared to the CRLM group (72 ± 154 mL); p = 0.03. Baseline alkaline phosphatase (AP) and TGF-ß1 blood levels were notably higher in the CRLM group. Immunohistochemical analysis indicated a higher proportion of CRLM patients with high TGF-ß1 expression in liver tissues compared to the control group (p = 0.034). Correlation analysis showed that resected liver volume, baseline plasma HGF, AP, and albumin levels significantly correlated with liver regeneration volume. However, in multivariable analysis, only resected liver volume (ß: 0.31; 95% CI: 0.14-0.47, p = 0.01) remained significant. In conclusion, this study highlights compromised liver regeneration in CRLM patients post-chemotherapy. Additionally, these patients exhibited lower serum TGF-ß1 levels and reduced TGF-ß1 expression in liver tissue, suggesting TGF-ß1 involvement in mechanisms hindering liver regeneration capacity following major resection after chemotherapy.

Combined Femtosecond Laser Glass Microprocessing for Liver-on-Chip Device Fabrication.

Nowadays, lab-on-chip (LOC) devices are attracting more and more attention since they show vast prospects for various biomedical applications. Usually, an LOC is a small device that serves a single laboratory function. LOCs show massive potential for organ-on-chip (OOC) device manufacturing since they could allow for research on the avoidance of various diseases or the avoidance of drug testing on animals or humans. However, this technology is still under development. The dominant technique for the fabrication of such devices is molding, which is very attractive and efficient for mass production, but has many drawbacks for prototyping. This article suggests a femtosecond laser microprocessing technique for the prototyping of an OOC-type device-a liver-on-chip. We demonstrate the production of liver-on-chip devices out of glass by using femtosecond laser-based selective laser etching (SLE) and laser welding techniques. The fabricated device was tested with HepG2(GS) liver cancer cells. During the test, HepG2(GS) cells proliferated in the chip, thus showing the potential of the suggested technique for further OOC development.

Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia.

Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.

Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis.

Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation.

Custodiol-N Is Superior to Custodiol® Solution in Experimental Rat Uterus Preservation.

Uterus transplantation (UTx) is the first and only available treatment for women with absolute uterine factor infertility. However, clinical application is limited by the lack of organs, ischemia/reperfusion injury, as well as immunosuppression after UTx. Several different preservation solutions are used in experimental and clinical UTx, including Custodiol® solution. Recently, the novel Custodiol-N solution was developed with superior results in organ preservation. However, the solution was not tested yet in UTx. Therefore, the aims of this study were to evaluate the effect of Custodiol-N in uterus prolonged cold preservation time (8 and 24 h), compared to Custodiol® solution. Uterus tissue samples were obtained from adult Sprague Dawley rats (n = 10/group). Cold ischemic injury was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. After 8 h of cold ischemia, higher percentage of tissue edema, necrosis signs and myeloperoxidase expression, as well as lower superoxide dismutase activity were found in Custodiol® compared to Custodiol-N (p < 0.05). These differences were more pronounced after 24 h of cold preservation time (p < 0.05). This study demonstrated that Custodiol-N protects uterus grafts from cold ischemic injury better than standard Custodiol® most likely via inhibition of oxidative stress and tissue edema. It seems that iron chelators in the composition of Custodiol-N play an important protective role against cold ischemia.

The Role of Metabolomics in Current Concepts of Organ Preservation.

In solid organ transplantation (Tx), both survival rates and quality of life have improved dramatically over the last few decades. Each year, the number of people on the wait list continues to increase, widening the gap between organ supply and demand. Therefore, the use of extended criteria donor grafts is growing, despite higher susceptibility to ischemia-reperfusion injury (IRI) and consecutive inferior Tx outcomes. Thus, tools to characterize organ quality prior to Tx are crucial components for Tx success. Innovative techniques of metabolic profiling revealed key pathways and mechanisms involved in IRI occurring during organ preservation. Although large-scale trials are needed, metabolomics appears to be a promising tool to characterize potential biomarkers, for the assessment of graft quality before Tx and evaluate graft-related outcomes. In this comprehensive review, we summarize the currently available literature on the use of metabolomics in solid organ Tx, with a special focus on metabolic profiling during graft preservation to assess organ quality prior to Tx.

The role of melatonin in colorectal cancer treatment: a comprehensive review.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide, known as the second leading cause of cancer-related deaths annually. Currently, multimodal treatment strategies, including surgical resection, combined with chemotherapy and radiotherapy, have been used as conventional treatments in patients with CRC. However, clinical outcome of advanced stage disease remains relatively discouraging, due mainly to appearance of CRC chemoresistance, toxicity, and other detrimental side effects. New strategies to overcome these limitations are essential. During the last decades, melatonin (MLT) has been shown to be a potent antiproliferative, anti-metastatic agent with cytotoxic effects on different types of human malignancies, including CRC. Hence, this comprehensive review compiles the available experimental and clinical data analyzing the effects of MLT treatment in CRC patients and its underlying molecular mechanisms.

Ischemia and reperfusion injury in uterus transplantation: A comprehensive review.

Uterus transplantation (UTx) is the only available treatment for human beings who cannot carry children out to term. However, despite several clinical studies with a very limited number of UTx many issues have to be addressed. Up to date, there is a limited number of successful UTx with livebirth and the majority was achieved with live donors. Wide clinical application is inherently limited by the lack of organs, ischemia/reperfusion injury (IRI) as well as immunosuppression after UTx. The objective of this comprehensive literature review is to discuss these arising limitations of UTx with main focus on strategies to reduce IRI. This review showed, that usage of immunosuppressants, opioids or supplements, like amino acids, protects uterus from IRI, improving rising level of antioxidants and decreasing level of oxidative stress markers. The available data of experimental and clinical studies was compiled and will be discussed.

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects.

Due to higher vulnerability and immunogenicity of extended criteria donor (ECD) organs used for organ transplantation (Tx), the discovery of new treatment strategies, involving tissue allorecognition pathways, is important. The implementation of machine perfusion (MP) led to improved estimation of the organ quality and introduced the possibility to achieve graft reconditioning prior to Tx. A significant number of experimental and clinical trials demonstrated increasing support for MP as a promising method of ECD organ preservation compared to classical static cold storage. MP reduced ischemia-reperfusion injury resulting in the protection from inadequate activation of innate immunity. However, there are no general agreements on MP protocols, and clinical application is limited. The objective of this comprehensive review is to summarize literature on immunological effects of MP of ECD organs based on experimental studies and clinical trials.

Recurrent laryngeal nerve injury assessment by intraoperative laryngeal ultrasonography: a prospective diagnostic test accuracy study.

INTRODUCTION: Recurrent laryngeal nerve injury is one of the major complications related to thyroid surgery. Intraoperative recurrent laryngeal nerve functional status monitoring is becoming a standard part of thyroid surgery. However, the current methods for intraoperative nerve functional status assessment are associated with a demand for specialized devices and increased costs. AIM: To assess the validity of a new method - intraoperative laryngeal ultrasonography - for prediction of recurrent laryngeal nerve injury. MATERIAL AND METHODS: This prospective diagnostic test accuracy study included 112 patients undergoing thyroid surgery in Vilnius University Hospital Santaros Clinics. Neurostimulation combined with laryngeal ultrasonography and laryngeal palpation was performed intraoperatively to evaluate recurrent laryngeal nerve functional status. Recurrent laryngeal nerve injury was confirmed by laryngoscopy, which was performed on the first postoperative day and considered to be the gold standard method. RESULTS: Data on 112 consecutive patients and 200 nerves at risk were collected. The temporary vocal cord palsy rate was 5.4% per patient and 3% per nerve at risk. No permanent palsy or bilateral injury cases were registered in the study cohort. Laryngeal ultrasound sensitivity counted per nerve at risk was 83.3%, specificity 97.2%, accuracy 96.4%, positive predictive value 62.5% and negative predictive value 99%. CONCLUSIONS: Laryngeal ultrasonography is a feasible new technique for accurate intraoperative recurrent laryngeal nerve injury evaluation.

Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules.

BACKGROUND: Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. METHODS: A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. RESULTS: A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. CONCLUSIONS: Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).

Laparoscopic distal resection of the pancreas. Can be all resections of body and tail of the pancreas called the same?

INTRODUCTION: Distal resection of the pancreas is a routine procedure in high-volume centres. However, the volume of this procedure can vary. This variation plays a very important role in laparoscopic approach of pancreatic surgery and can be a real challenge if the anatomical situation is underestimated. AIM OF THE STUDY: To present our experience in minimally invasive treatment of the pancreatic tumours and to discuss different approaches to different anatomical situations. MATERIAL AND METHODS: We performed a retrospective analysis of patients, who underwent laparoscopic pancreas resection for pancreatic cancer in our hospital since 2014 to 2016 February. According to extension of operation, patients were divided into two groups: distal pancreatectomy and left hemipancreatectomy for cases that required preparation of the portal vein. Demographic characteristics, and operative and postoperative data were compared between both groups. RESULTS: Out of 16 patients, distal pancreatectomy was performed for 7 (43.8%) and left hemipancreatectomy for 9 (56.2%) patients. For 1 (14.3%) laparoscopic distal pancreatectomy and for 2 (22.2%) laparoscopic left hemipancreatectomy patients surgical conversion to laparotomy was performed. The average operation time was 205 (195-245) min for distal pancreatectomy and 412.5 (280-520) min for left hemipancreatectomy group (p = 0.001), blood loss 125 (20-250) ml and 250 (50-1800) ml accordingly (p = 0.138). Totally postoperative fistula occurred in 7 (43.8%) cases; out of them, 5 (71.4%) patients were from the left hemipancreatectomy group. CONCLUSIONS: Laparoscopic left hemipancreatectomy is more complicated than distal pancreatectomy. Extension and technique selection of distal resection of the pancreas depends on the Yonsei criteria and tumour relation to the portal vein.

The utility of the Bethesda category and its association with BRAF mutation in the prediction of papillary thyroid cancer stage.

PURPOSE: This study aims to determine the utility of the Bethesda category and its association with BRAF mutation in prediction of the papillary thyroid cancer (PTC) stage. METHODS: A prospective study analyzed patients who had ultrasound-suspicious thyroid nodules, underwent FNA and cytological examination, and were classified according to the Bethesda system. Patients from Undetermined Significance Or Follicular Lesion Of Undetermined Significance (AUS/FLUS), Follicular Neoplasm or Suspicious for a Follicular Neoplasm (FN/SFN), Suspicious for Malignant Cells (SMC), and Positive for Malignant Cells (PMC) groups were examined for the BRAF mutation and had a thyroid surgery. Demographical and histological features and stage of the disease were evaluated for PTC patients in accordance with the Bethesda category and its association with BRAF mutation. RESULTS: Three hundred eight of all patients underwent operation. One hundred forty-three (46.4%) of them were diagnosed with PTC. In 14 (9.8%) PTC cases, FNA biopsies were classified as AUS/FLUS, 23 (16.1%) as FN/SFN, 41 (28.7%) as SMC, and 65 (45.5%) as PMC. I-II stages of PTC were diagnosed for 88 (61.5%) patients and III-IVA for 55 (38.5%). Patients from the SMC and PMC groups had larger tumors, higher incidence of lymph node metastases, classical PTC type, B-type Raf (BRAF) positive, and III-IVA stage cancer, than patients from the AUS/FLUS and FN/SFN groups. When comparing 27 (18.9%) BRAF-negative patients from the AUS/FLUS and FN/SFN groups with 116 (81.1%) BRAF-negative patients from the SMC and PMC groups and all BRAF-positive patients, the prediction of more aggressive histological features and stage was slightly improved. CONCLUSIONS: Higher Bethesda categories are associated with higher stages of PTC. Association of the Bethesda category with BRAF mutation can slightly improve the value of stage prediction.

Laparoscopic approach in the treatment of large epiphrenic esophageal diverticulum.

Epiphrenic diverticulum of the lower third of the esophagus is a relatively rare disorder. We present the case of a large, 7.5 cm diameter esophageal epiphrenic diverticulum treated by the laparoscopic approach. Surgery was indicated by the severity of the patient's symptoms and size of the diverticulum. A laparoscopic transhiatal diverticulectomy with a myotomy and Dor fundoplication was carried out. The overall operative time was 180 min. The patient tolerated the surgery well and was discharged from hospital 4 days after the surgery. From the 10(th) postoperative day the patient resumed a regular diet. Four weeks after the operation the patient had no complaints, symptoms of dysphagia or vomiting. The laparoscopic approach in the treatment of a large, 7.5 cm epiphrenic diverticulum of the esophagus is feasible, safe and well tolerated by the patient.