Immunoexpression of Ki67, P16 and Beta-catenin in precursor lesions of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, after basal cell carcinoma, representing about 10-20% of all malignant skin tumors. The mortality rates of CSCC approach those of renal and oropharyngeal carcinomas, as well as melanoma, with the increasing of the risk once metastases and perineural invasion occur. Both actinic keratosis (AK) and Bowen's disease (BD) are direct precursors with the potential for progression to CSCC. In this study, we analyzed the expression of Ki67, P16 and Beta-catenin in the precursor lesions of CSCC in relation to histological prognostic parameters, respectively between them, with the aim of identifying possible correlations with a role in prognosis. Ki67 and P16 presented higher scores in advanced precancerous lesions, such as keratinocyte intraepithelial neoplasia (KIN) III and BD and low scores in seborrheic keratosis (SK). The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Giant exophytic gastrointestinal stromal tumor (GIST) causing gastric outlet obstruction: case report and review of literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, mostly located within the stomach. About 30% of GISTs are incidentally diagnosed and as they become symptomatic may be associated with bleeding, bowel obstruction or spontaneous rupture. CASE PRESENTATION: We present the case of a middle-aged patient diagnosed with a giant gastric GIST, which presented for intermittent gastric outlet obstruction symptoms, and emphasize the major imagistic, histopathological, and therapeutic challenges that may be encountered. There are only several cases of gastric exophytic gastric GIST provoking intermittent gastric outlet obstruction. Tumor resection should be adapted to every patient's status, focused on en bloc extraction, with preservation of invaded organs as much as possible.

Clinical, histopathological and immunohistochemical study of keratoacanthoma.

Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.

The perioperative effect of anesthetic drugs on the immune response in total intravenous anesthesia in patients undergoing minimally invasive gynecological surgery.

BACKGROUND: The specific mechanism of action of each anesthetic drug on the immune system is still incompletely known. It is important to know how the various anesthetics used in minimally invasive surgery (MIS) act on the inflammatory response because the choice of the anesthetic agent can influence the patient's immune system. AIM: Evaluation of the effect of anesthetic drugs used for total intravenous anesthesia (Propofol and Midazolam) on the inflammatory response after minimally invasive gynecological surgery. PATIENTS, MATERIALS AND METHODS: The inflammatory response in 20 female patients who underwent minimally invasive gynecological surgery under which intravenous anesthesia was performed. Depending on the combination of anesthetics used, we subdivided the study group into two groups, Group 1 consisting of the patients (n=10) who were given for total intravenous anesthesia, the combination with Midazolam+Fentanyl, and Group 2 (n=10) the patients who received the combination of Propofol+Fentanyl, respectively. Surgical interventional procedures included day surgery: diagnostic and operative hysteroscopy, endometrial ablation, surgical treatment of vulvar disorders. Serological profiling of patients was performed by dosing the serum concentration of nucleotide-binding domain (NOD) and leucine-rich repeat protein 3 (NLRP3) inflammasomes, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), IL-10 before and two hours after the surgical procedure. RESULTS: In our study, we found that in both groups of patients (Midazolam+Fentanyl - Group 1, Propofol+Fentanyl - Group 2), NLRP3 and cytokines concentrations in the serum were higher after MIS than those before MIS. CONCLUSIONS: It appears that both Midazolam and Fentanyl and Propofol and Fentanyl have an immunomodulatory action due to the anti-inflammatory effect of both anesthetics. Therefore, anesthesiologists must choose an anesthetic method that uses individualized anesthetic agents, depending on the patient's immune status and disease.

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.

Microglial morphology determined with confocal and two-photon laser scanning microscopy.

Microglia are the first and main form of active immune defense in the nervous system. The immune status of microglia is directly correlated to their morphology. Therefore, microglia morphology is used to distinguish between active and surveilling microglia. For the actual paper, we used confocal laser scanning microscopy (cLSM) and two-photon laser scanning microscopy (2P-LSM), to investigate microglia morphology of 14-16 weeks old male, transgenic mice (n=6). After obtaining, in vivo and fixed tissue, single cells images, we manually tracked individually branch segments of normal microglia. The total number of branches and their overall length were analyzed. Additionally, the number and mean length of each branch order were measured. The overall microglia branching morphology was not different between the two acquisition methods. However, a higher number of fifth branches was observed using cLSM and 2P-LSM, in both fixed and in vivo tissue. Although results from the two methods are mainly comparable, small differences between them should be taken in consideration when formulating an activating∕surveilling conclusion that is purely based on pure microscopic findings. Furthermore, in our opinion, due to their highly dynamic nature, microglia should be carefully labeled as resting or active, taking also into consideration the imaging method used to obtain the data.

Stage IV duodenal GIST requiring emergency pancreaticoduodenectomy - diagnosis difficulties and therapeutic options.

This paper presents a very rarely encountered case of a 45-year-old female, admitted in our Surgical Clinic for upper digestive bleeding (repeated hematochezia). The upper endoscopy was negative, but the barium meal discovered an apparently extrinsic duodenal (D3) stenosis; abdominal ultrasound diagnosed a left liver mass suggesting a metastatic tumor. The hematochezia relapse, with hemodynamic instability imposed emergency surgery; on laparotomy, a bleeding tumor located on the duodenopancreatic region was discovered, and a pylorus-preserving pancreaticoduodenectomy (Traverso-Longmire) was performed. The histology and immunohistochemistry established the diagnosis of duodenal stromal tumor, CD34 and CD117 positive, with an estimated progression risk of 34%. The postoperative evolution was favorable, the patient being alive, four years after the surgery.

Severe upper gastrointestinal bleeding determined by a gastric lymphoma associated with Helicobacter pylori-positive atrophic gastritis.

The pathogenesis of gastric cancer regardless of histological structure is a classic example of gene-environment interaction, and an important epidemiological aspect was the recognized association with Helicobacter pylori infection. This paper describes a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in a young patient whose first sign of the disease was upper gastrointestinal bleeding and associated hemorrhagic shock. The patient is a 31-year-old man, diagnosed by endoscopy 10 years ago with H. pylori-positive chronic atrophic gastritis, who refused treatment to eradicate the bacterium and presents currently in the emergency room for serious upper gastrointestinal bleeding. Emergency upper gastrointestinal tract endoscopy highlights the presence of bleeding gastric tumors. It was a surgical emergency and intra-operatively the presence of invasive gastric cancer into the left hepatic lobe was noted which required total gastrectomy with the purpose of hemostasis. Immediate and remote postoperative evolution was favorable and post-operative follow-up at six months, 12 months, and 24 months showed no signs of local or distance occurrence.

Squamous esophageal carcinoma and mucinous adenocarcinoma of the colon - an unusual association.

The existence of a simultaneous cancer of the esophagus and colon is a rare situation that recognizes an increased incidence in recent years in the world, probably as a result of the improved measures of diagnosis and treatment, as well as the development of screening programs. The aim of this work is to present a case of synchronous esophageal squamous carcinoma with mucinous adenocarcinoma of the hepatic angle of the colon. The patient was hospitalized to our Surgical Clinic with the thoracic squamous esophageal carcinoma diagnosis. On admission, symptoms were dominated by overall dysphagia, patient showing a weight loss of 10 kg for the last 30 days. Preoperative imaging tests did not revealed regional or distant metastatic disease. Preoperative colonoscopy was incomplete (only until the splenic angle of the left colon) due to the insufficient mechanical preparation. On laparotomy, a carcinoma of the hepatic angle of the colon, partially stenosing was discovered. An upper pole esogastrectomy with intrathoracic esogastrostomy and a right colectomy with ileotransversostomy were practiced, at the same operative session. Postoperative evolution was poor and the patient died on the ninth day from the surgery during an alcohol withdrawal crisis.

c-abl and YWHAZ gene expression in gastric cancer.

This study aims to determine the gene expression for c-abl and YWHAZ in gastric cancer and the differences between the c-abl and YWHAZ gene expression inside the tumor versus healthy tissue (at the resection edges). This prospective study included 34 patients with gastric neoplasia, 21 men and 13 women, aged between 49 and 79 years (65.5 years median). After the surgical procedure, in these cases, we collected two tissue samples: one sample was obtained from inside the tumoral tissue and another sample from the gastric tissue, which was identified as normal apparently, as far as possible from the tumor (resection edge). For determining the c-abl and YWHAZ gene expression, we used the quantitative real-time polymerase chain reaction. Regarding the c-abl gene expression in gastric cancer, c-abl expression was identified as lower inside tumor cells comparing to the normal gastric tissue (resection limit). This difference of gene expression emphasize the role of the c-abl gene in normal tissue growth and the involvement in apoptosis induction when alteration of DNA occurs, as a result to different agents actions as stress, ionizing radiations. The loss of expression or even the down-regulation of the c-abl is a fundamental event that leads to genesis and progression of tumors. No significant differences of the YWHAZ gene expression between the tumoral and normal gastric tissue probes were recorded in our study.

Microglial voltage-gated sodium channels modulate cellular response in Alzheimer's disease--a new perspective on an old problem.

Alzheimer's disease (AD) determines gradual loss of cognition and memory function, eventually leading to clinical manifest dementia. The pathogenic mechanisms of AD remain elusive and treatment options unsatisfactory, targeting only symptoms like memory loss, behavior changes, sleep disorders and seizures. These therapies are not stopping the disease's progression, at their best they can only delay it. Accumulating evidence suggests that AD is associated with a microglial dysfunction. Microglia are resident immune cells that provide continuous surveillance within the brain. When excessively activated, microglial response can also have detrimental effects via the exacerbation of inflammatory processes and release of neurotoxic substances. Recently, it was recognized that microglia express voltage-gated ion channels, in particularly voltage-gated sodium channels (VGSC). Pharmacological block of VGSC has been attempted symptomatically in AD to control the epileptic features often associated with AD, as well as to relieve detrimental behavioral and psychological symptoms of dementia. The success of VGSC treatment in AD was unexpectedly variable, ranging from very beneficial to plain detrimental. This variability could not be satisfactorily explained solely by the neuronal effects. This article will try to discuss possible implication of microglial VGSC dysfunction in AD according to available data, own personal experience of the authors and propose a new way to investigate its possible implications.

The sentinel lymph node (SLN) significance in colorectal cancer: methods and results. General report.

Colorectal cancer appears to be one of the most important malignancies in the world, with a survival rate depending on the TNM stage. The presence of lymph nodes metastasis indicates the necessity of adjuvant chemotherapy but exact classification of the N stage requires at least 12 lymph nodes to be pathologically examined. The sentinel lymph node (SLN) is considered to be the closest lymph node to the tumor, bearing the highest risk of malignant cells colonization. The main advantage of the sentinel lymph node mapping in colorectal cancer is identification and separate pathological examination of the nodes carrying the highest risk of metastasis. There are still open questions regarding the best method for sentinel lymph node mapping (in vivo or ex vivo), the factors influencing it, which substance is better for identification and which are the best histological methods and markers to be used. Numerous studies have discussed the quality and applicability of the method, but the importance of the SLN in colorectal carcinoma remains an open issue.

Extrarenal retroperitoneal angiomyolipoma with unusual evolution.

The aim of this paper is to present the case of an extrarenal retroperitoneal angiomyolipoma with unusual evolution, due to the herniation through the inguinal canal, determining an extraperitoneal hernia. A ureteral duplicity and associated hydronephrosis contributed to the peculiarity of the case. The case was operated (en block tumor and right kidney removal), the postoperative evolution being favorable at seven years after the surgery.