Sympathetic Nervous Influences Are Negative Prognostic Factors in Stomach Cancer.

(1) Background: The aim of our study was to assess the involvement of the sympathetic nervous system in the progression of patients with gastric carcinoma by analyzing the sympathetic neuronal fibers and beta 2 adrenoreceptors. (2) Methods: We performed a retrospective study in which we analyzed the clinical, biological, and histological data from a total of 104 patients diagnosed with stomach cancer. (3) Results: After analyzing the immunoreactivity of beta 2 adrenoreceptors, we observed increased values in patients with tumors larger than 5 cm in diameter (p = 0.0371), with a deeper degree of tumor invasion T3-4 (p = 0.0159), invasion in more than two lymph nodes (p = 0.0462), or a TNM stage III-IV. Regarding the survival analysis, better survival rates (65%) were observed for patients with a low value of beta 2 adrenoreceptors (B2A-), compared to B2A (+) patients, in which survival at 3 years of follow-up was only 43%. In addition, the analysis of intra-tumoral sympathetic fibers showed a better survival rate (83%) for patients with a low value of density compared to patients with increased density, in whom the survival rate was only 24%. (4) Conclusions: The findings of this study indicate that patients with stomach cancer have a more unfavorable prognosis when they have a higher density of sympathetic nerve fibers and an increased expression of beta 2 adrenergic receptors inside the tumor.

The Assessment of Heart Rate Variability in Patients with Pancreatic Cancer.

The aim of our study is to provide an assessment of heart rate variability (HRV) as a predictor for the survival of patients with pancreatic cancer (PCa). We conducted a retrospective, descriptive study. 53 consecutive patients who were newly diagnosed with pancreatic cancer (PCa), were included. In the end, 41 patients were included in the analysis, out of which 14 patients survived at least until the 24-month follow-up, while 27 patients died within 24 months from the diagnosis. These patients were monitored with 24-hour Holter electrocardiogram (ECG) prior to the initiation of any therapy for determining heart rate variability. To establish the cut-off values of HRV, 24-hour Holter ECG recordings of 20 healthy subjects were analyzed. In addition to heart rate analysis, HRV indices were also analyzed: SDNN, rMSSD, ULF and VLF. Median survival in patients with low value of SDNN was 9 months, compared to patients with hight SDNN where median survival was 15 months (Hazard ratio 2.301, 95% CI of ratio 0.9080 to 5.833, p= 0.034). Although low values of the HRV indices in the frequency domain were associated with reduced survival, no statistically significant differences were recorded. The reduction of heart rate variability indices is a negative prognostic factor in patients newly diagnosed with pancreatic cancer.

Exploring the Prevalence of PTSD in Hand Trauma: A Comprehensive Study.

Hand trauma is a common and debilitating condition that can have significant physical, functional, and psychological effects on individuals. This study used a case-control design to investigate the frequency and factors associated with symptoms of post-traumatic stress disorder (PTSD) in a sample of individuals with complex hand and forearm injuries. Our hypothesis suggests that demographic data, among other factors, influences the intensity of PTSD symptoms measured by the PCL-5 scale three months post-surgery. This study included 166 individuals, 142 males and 24 females, with an average age of 42.14 years (SD = 12.71). Our study found significant associations between symptoms of PTSD and various demographic and clinical factors. PTSD symptoms were observed in females, individuals from specific regions, and certain socio-professional groups. Furthermore, educational attainment and personal background have been identified as significant factors in the development of PTSD. The role of trauma type was crucial, amputees and fractures were more prone to developing PTSD. A strong link was found between increased symptoms of PTSD and negative postoperative outcomes, including amputation of necessity and the need for additional surgery. The absence of family support exacerbates the psychological distress of trauma survivors. The findings highlight the intricate nature of PTSD development and underscore the significance of a comprehensive postoperative treatment strategy encompassing psychological assessment and support.

Clinical Outcomes Depending on Sympathetic Innervation in Pancreatic Cancer.

BACKGROUND: The aim of our study was to evaluate sympathetic neuronal remodeling in patients with pancreatic cancer, together with its correlation with clinical outcomes. METHODS: In this descriptive, retrospective study, we analyzed pancreatic cancer specimens and peritumoral pancreatic tissue from 122 patients. We also investigated tyrosine hydroxylase immunoreactivity for the analysis of sympathetic nerve fibers and beta 2 adrenoreceptors immunoreactivity. To investigate the potential interaction between tyrosine hydroxylase (TH), beta 2 adrenoreceptors (B2A) immunoreactivity, and clinicopathological outcomes, we used the median to classify each case as TH+, respectively, B2A+ (if it presented a value higher than the median). RESULTS: Firstly, the overall survival was analyzed according to TH and B2A immunoreactivity, in both intratumoral and peritumoral tissue. Only B2A immunoreactivity in the peritumoral pancreatic tissue influenced overall survival at 5 years of follow-up; thus, B2A+ patients recorded a 5-year survival of only 3% compared to B2A- patients who recorded an overall survival at 5 years of follow-up of 14% (HR = 1.758, 95% CI of ratio 1.297 to 2.938, p = 0.0004). Additionally, the increased immunoreactivity of B2A in the peritumoral tissue was also associated with other factors of poor prognosis, such as moderately or poorly differentiated tumors, the absence of response to first-line chemotherapy, or metastatic disease. CONCLUSIONS: The increased immunoreactivity of beta 2 adrenoreceptors in pancreatic peritumoral tissue represents a poor prognostic factor in pancreatic cancer.

Retrospective Study of a Patient with Multiple de Novo Skin Tumor Formations.

In Romania, the incidence of malignant melanocytic tumors is continuously increasing. According to the World Health Organization, the incidence of melanocytic and non-melanocytic skin neoplasms has increased considerably and globally, in the last decade. We present the case of a 49-year-old patient who, over the course of 7 years, came in the Plastic Surgery Clinic of the Emergency County Hospital of Craiova for the excision of a number of 25 skin tumor formations, located on the face, cervical region, trunk and upper limbs. Treatment included complete microsurgical excision and supervision. In the end, the patient's treatment compliance decreased significantly.

Genomic Profiling - A Need for Clinical Decision? -Case Reports.

Cancer is still an important health issue worldwide due to increased incidence and mortality. Personalized medicine is the future of cancer treatment. Development in technology improved technical skills in DNA/RNA sequencing. NGS technology in solid-tumor samples can describe DNA or RNA analysis by including the entire genome to detect clinical relevant mutations. Genetic results may be considered having a dynamic impact because of heterogenous molecular alterations depending of time and treatment influence. We conducted a retrospective study of all NGS tests made in the last five years for the patients from 'Sf. Nectarie' Oncology Center, Craiova, Romania. We selected three relevant clinical cases where NGS analysis was performed and the results changed the perspective of the clinical decision. Our aim is to evaluate the importance of NGS results in clinical approach. Although medicine known an important development during the last decades, only a few patients can benefit of advanced personalized treatments. It is still hard to identify the alterations or gene mutations because of genetic tests are not easily available and only a small proportion of patients carries genetic alterations.

Immunohistochemical expression of p53, Ki67, α-SMA, CD44 and CD31 in different histological subtypes of basal cell carcinoma.

Basal cell carcinoma (BCC) is a common, locally invasive tumor that arises within sun-damaged skin and rarely develops on the palms and soles or mucous membranes. Men generally have higher rates of BCC than women. Incidence also increases with age and the median age of diagnosis is 68 years old. Mortality from BCC is rare and cases of aggressive, local destructive, metastatic BCCs are more likely from tumors with aggressive histopathological (HP) patterns. The aim of this study was to investigate and correlate the immunohistochemical expression of p53, Ki67, alpha-smooth muscle actin (α-SMA), cluster of differentiation (CD)44 and CD31 with both aggressive and nonaggressive types of BCCs. In our study, we observed a varied staining pattern for p53, with the highest reactivity noticed in the peripheral palisading zone. The staining pattern for Ki67 was similar to p53, with a more pronounced reaction in the periphery of the tumor. We found different Ki67 and p53 expression among the various subtypes of BCC. The CD31 reactivity, mostly seen in the stroma, was positive in all BCCs and varied significantly between its different HP subtypes. Regarding stromal expression of α-SMA, the adenoid and basosquamous types had the most intense reaction in our study. The CD44 tumor expression was correlated in our study to the aggressive pattern of BCCs.

Treatment of skin defects with PRP enriched with hyaluronic acid - histological aspects in rat model.

Tissue healing is a complex, dynamic process, characterized by the replacement of devitalized and absent cell and tissue structures. This can be obtained by different methods, these being found in the "reconstructive scale", which although it is very rich does not offer a universally valid solution for closing skin wounds. In plastic surgery, platelet-rich plasma (PRP) has proven effective in the treatment of skin graft donor areas, burn wounds, skin grafts, tendons, or varicose ulcers. Also, hyaluronic acid (HA) has found its utility in different areas of medicine, other than the esthetics field, with satisfactory results after its use in various lesions. The aim of our study was to find a method of healing wounds with skin defect that shortens the time of complete epithelialization compared to native healing, which is accessible to any patient both by its simplicity and by the lowest possible costs. So, we decided to test a preparation consisting of PRP and granular HA in this type of wounds on a group of 30 Wistar rats. Corroborating the macroscopic data with the microscopic ones, an important similarity can be observed between the healing of the adjuvant-treated lesion at 14 days postoperatively and the healing of the lesion left to natural healing at 21 days, thus shortening the healing period by seven days.

Clinical impact of wireless capsule endoscopy for small bowel investigation (Review).

Wireless capsule endoscopy is currently considered the gold standard in the investigation of the small bowel. It is both practical for physicians and easily accepted by patients. Prior to its development, two types of imaging investigations of the small bowel were available: radiologic and endoscopic. The first category is less invasive and comfortable for patients; it presents the ensemble of the small bowel, but it may imply radiation exposure. Images are constructed based on signals emitted by various equipment and require special interpretation. Endoscopic techniques provide real-time colored images acquired by miniature cameras from inside the small bowel, require interpretation only from a medical point of view, may allow the possibility to perform biopsies, but the investigation only covers a part of the small bowel and are more difficult to accept by patients. Wireless capsule endoscopy is the current solution that overcomes a part of the previous drawbacks: it covers the entire small bowel, it provides real-time images acquired by cameras, it is painless for patients, and it represents an abundant source of information for physicians. Yet, it lacks motion control and the possibility to perform biopsies or administer drugs. However, significant effort has been oriented in these directions by technical and medical teams, and more advanced capsules will surely be available in the following years.

Role of Contrast-Enhanced Ultrasonography in Hepatocellular Carcinoma by Using LI-RADS and Ancillary Features: A Single Tertiary Centre Experience.

Clinical utility of ancillary features (AFs) in contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS®) is yet to be established. In this study, we assessed the diagnostic yield of CEUS LI-RADS and AFs in hepatocellular carcinoma (HCC). We retrospectively included patients with risk factors for HCC and newly diagnosed focal liver lesions (FLL). All lesions have been categorized according to the CEUS LI-RADS v2017 by an experienced sonographer blinded to clinical data and to the final diagnosis. From a total of 143 patients with 191 FLL, AFs favoring HCC were observed in 19.8% cases as hypoechoic rim and in 16.7% cases as nodule-in nodule architecture. From the total of 141 HCC cases, 83.6% were correctly classified: 57.4%- LR-5 and 26.2%- LR-4. In 9.21% cases, CEUS indicated LR-M; 2.12% cases- LR-3. The LR-5 category was 96.2% predictive (PPV) of HCC. LR-5 had 60.4% sensitivity and 93.6% specificity. PPV for primitive malignancy (LR-4 + LR-5) was 95.7%, with 88% sensitivity, 89.3% specificity and 88.4% accuracy for HCC. LR-4 category had 94.8% PPV and 26.2% sensitivity. CEUS LR4 + LR5 had 81,8% sensitivity for HCCs over 2 cm and 78.57% sensitivity for smaller HCCs. CEUS LR-5 remains an excellent diagnostic tool for HCC, despite the size of the lesion. The use of AFs might improve the overarching goal of LR-5 + LR-4 diagnosis of high specificity for HCC and exclusion of non-HCC malignancy.

Clinical Study on the Increased Incidence of Nodular Melanoma Cases Compared to Superficial Melanoma.

Our study group was comprised of 67 patients with melanoma, admitted and operated in our clinic between 2010-2018. Only the patients with melanoma localized on the head, torso and upper limb were selected for our study. We attempted to establish a link between the clinical appearance, presence or absence of ulceration, presence or absence of regional lymphadenopathy or distant metastases, surgical technique, histopathological type, Clark level and Breslow depth, disease stage (TNM), adjuvant therapies and survival rates at 1, 3, 5 and 10 years.

Evaluation of Hepatocellular Carcinoma Patients: Interim Analysis of Cases from a Tertiary Referral Center in Craiova, Romania.

Although medicine is constantly evolving, hepatocellular carcinoma remains a pathology with a poor prognosis due to the frequent delayed diagnosis and the aggressiveness of the disease. AIM: Our objective was to evaluate liver function and stage of disease of newly diagnosed HCC patients. METHODS: We conducted a retrospective study between July 2016 and January 2021 and we included hospitalized patients within the Department of Gastroenterology of the Emergency County Hospital of Craiova. We identified 119 newly diagnosed patients and we collected data from patient history, contrast-enhanced imaging and laboratory analysis. RESULTS: 81 patients were diagnosed in BCLC Stage A and B. Liver function was not significantly modified, despite 91.5% of the patients presented with elevated AST levels. Because of the cirrhotic liver already affected, 73 patients had thrombocytopenia. Contrast-enhanced ultrasound was performed in 79 patients, as a complementary imaging exploration. Alfa-fetoprotein values could not be correlated with the severity of disease. CONCLUSIONS: Early diagnosis was mostly established. It is mandatory for treatment management and overall survival to follow a rigorous surveillance of patients at risk for HCC.

The Prognostic Correlation of Heart Rate Variability at Diagnosis with Survival of Patients with Hepatocellular Carcinoma.

BACKGROUND: Heart rate variability (HRV) indices have been shown to be associated with prognosis in various types of cancer. This study aims to assess the ability of these indices to predict survival in hepatocellular carcinoma (HCC) patients after diagnosis. METHODS: We retrospectively collected data from 231 patients diagnosed with HCC between January 2014 and March 2018. The baseline clinical-pathological variables and HRV indices (extracted from Holter electrocardiogram recordings) were analyzed. RESULTS: Univariate and multivariate analyses were performed to identify the predictive value of the above factors for overall survival (OS). The univariate analysis revealed that an age > 60 years, hepatitis C, portal vein involvement (thrombosis), a tumor size > 5 cm, alpha-fetoprotein (AFP) > 400 ng/mL, serum albumin, and C-reactive protein (CRP) were risk factors for poor OS. Multivariable Cox regression analyses identified that a tumor size > 5 cm and AFP > 400 ng/mL predict poorer outcomes in HCC patients. It should be mentioned that, in both the univariate analysis and in the multivariate analysis, between HRV indices, SDNN (standard deviation of all normal-to-normal (NN) intervals) < 110 ms was an independent risk factor for OS with an HR of 3.646 (95% CI 2.143 to 6.205). CONCLUSION: This study demonstrates that HRV indices identify HCC patients at high risk of death and suggests that such monitoring might guide the need for early therapy in these types of patients, as well as the fact that HRV can be a potential noninvasive biomarker for HCC prognosis.

Assessment of Epinephrine and Norepinephrine in Gastric Carcinoma.

The aim of our study was to assess the sympathetic nervous system's involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this system (epinephrine and norepinephrine), as well as by analyzing the histological expression of the norepinephrine transporter (NET). We conducted an observational study including 91 patients diagnosed with gastric carcinoma and an additional 200 patients without cancer between November 2017 and October 2018. We set the primary endpoint as mortality from any cause in the first two years after enrolment in the study. The patients were monitored by a 24-h Holter electrocardiogram (ECG) to assess sympathetic or parasympathetic predominance. Blood was also collected from the patients to measure plasma free metanephrine (Meta) and normetanephrine (N-Meta), and tumor histological samples were collected for the analysis of NET expression. All of this was performed prior to the application of any antineoplastic therapy. Each patient was monitored for two years. We found higher heart rates in patients with gastric carcinoma than those without cancer. Regarding Meta and N-Meta, elevated levels were recorded in the patients with gastric carcinoma, correlating with the degree of tumor differentiation and other negative prognostic factors such as tumor invasion, lymph node metastasis, and distant metastases. Elevated Meta and N-Meta was also associated with a poor survival rate. All these data suggest that the predominance of the sympathetic nervous system's activity predicts increased gastric carcinoma severity.

Expression of M3 muscarinic acetylcholine receptors in gastric cancer.

INTRODUCTION: Gastric cancer represents a real public health problem as far as incidence, aggressiveness and unfavorable prognosis are concerned. The autonomous nervous system might be one of the major factors involved in the onset, progression, and metastasis, both sympathetically and parasympathetically. The increased activation of the M3 muscarinic acetylcholine receptors (mAChRs) triggers pro-oncogenic mechanisms, especially at a gastric level, through the activation of the Hippo signaling pathway and the increase of the nerve growth factor. PATIENTS, MATERIALS AND METHODS: In this study, biopsy or postoperative gastric resection pieces have been evaluated by histopathological (HP) and immunohistochemical (IHC) examination in a group of 77 gastric patients and 23 patients without an oncological diagnosis. To quantify the IHC signal, also considering the HP aspect, light microscopy images were obtained. RESULTS: The M3 mAChR expression analysis has been correlated with the different gastric adenocarcinoma differentiation degrees (G1-G3). M3 mAChR presence has been observed also in the non-malignant gastric tissue, but it was significantly increased in the tumor tissue. The highest receptor expression was recorded in patients with a poorly-differentiated (G3) adenocarcinoma, these expressions decreasing with the increase of the differentiation degree towards moderately-differentiated (G2) and well-differentiated (G1). CONCLUSIONS: Surgical or pharmacological parasympathetic activity inhibition could decrease the development and progression of gastric tumors and could improve the gastric cancer patient's prognosis.

One stop shop approach for the diagnosis of liver hemangioma.

Hepatic hemangioma is usually detected on a routine ultrasound examination because of silent clinical behaviour. The typical ultrasound appearance of hemangioma is easily recognizable and quickly guides the diagnosis without the need for further investigation. But there is also an entire spectrum of atypical and uncommon ultrasound features and our review comes to detail these particular aspects. An atypical aspect in standard ultrasound leads to the continuation of explorations with an imaging investigation with contrast substance [ultrasound/ computed tomography/or magnetic resonance imaging (MRI)]. For a clinician who practices ultrasound and has an ultrasound system in the room, the easiest, fastest, non-invasive and cost-effective method is contrast enhanced ultrasound (CEUS). Approximately 85% of patients are correctly diagnosed with this method and the patient has the correct diagnosis in about 30 min without fear of malignancy and without waiting for a computer tomography (CT)/MRI appointment. In less than 15% of patients CEUS does not provide a conclusive appearance; thus, CT scan or MRI becomes mandatory and liver biopsy is rarely required. The aim of this updated review is to synthesize the typical and atypical ultrasound aspects of hepatic hemangioma in the adult patient and to propose a fast, non-invasive and cost-effective clinical-ultrasound algorithm for the diagnosis of hepatic hemangioma.

E-cadherin and aquaporin 1 co-expression analysis in hepatocellular carcinoma: a pilot study.

Hepatocellular carcinoma (HCC) is the main primary liver malignancy, being associated with both health and economic burden worldwide. Recently, novel molecular markers and possible therapeutic targets were identified. Different adhesion molecules, as well as possible angiogenesis-associated targets can be prime candidates when investigating novel therapies. Considering these premises, our goal was to study the co-existence of E-cadherin and aquaporin 1 (AQP1) in a series of HCC diagnosed patients. Utilizing archived tissue fragments from 17 patients diagnosed with well-to-moderate and poorly differentiated HCC, as well as four samples of normal liver tissue and using a highly specific biotin-free tyramide amplification technique, we have assessed here the expression of E-cadherin and AQP1 during HCC carcinogenesis. Moreover, as we have observed that some of the AQP1 expression seems membrane-bound, we have sought to evaluate their co-localization. Our data showed, as expected, that E-cadherin decreases from control tissue to low-grade and respectively, high-grade HCC. AQP1 was expressed, also as already known, at the level of endothelial blood vessels and bile ducts epithelia, however, we have showed here for the first time that this water pore is also expressed in the cytoplasm and membranes of hepatocytes, both in control and HCC tissue. Moreover, AQP1 expression parallels the decrease of E-cadherin expression during carcinogenesis, but together with this downregulation, we have also found a spatial decrease in the colocalization of the two proteins. Altogether, utilizing a biotin-free tyramide signal amplification technique, this study shows for the first time that AQP1 is expressed at the level of liver epithelia, in both control and HCC tissue.

The immunoexpression of MMP-1 and MMP-13 in eyelid basal cell carcinoma.

Basal cell carcinoma (BCC) is the most frequent human malignancy and at the same time the most frequent periocular malignancy, representing almost 80% of all non-melanoma skin cancers and 90% of eyelid cancers. The study included 50 cases of eyelid BCC, out of which 41 were nodular BCC (NBCC) and nine were infiltrative BCC (IBCC), with various Breslow scores (BS) and primary tumor (pT) category. We analyzed the immunoexpression of matrix metalloproteinases (MMPs) 1 and 13 in the tumoral epithelial component (TEC) and inflammatory stromal component (ISC) of BCC in relation to the two histopathological parameters. The immunoreaction for MMP-1 was identified in 41 (82%) cases and for MMP-13 in 46 (92%) cases both in the TEC and ISC of both types of BCC. The statistical analysis revealed that both collagenases had positive/high scores significantly associated with advanced BS. For MMP-1, there were statistical associations in TEC related to IBCC and high pT category, while MMP-13 only revealed statistical association in ISC with high pT. The presence of collagenase MMP-1 and MMP-13 expression in a high number of cases, both in TEC and ISC, confirms their intervention in the tumor progression and proposes these MMPs as potential targets in antineoplastic therapy.