A review of NTRK fusions in cancer.

The family of the neurotrophic tropomyosin kinase receptors (NTRK or TRK) is a part of the transmembrane tyrosine kinases responsible for neuronal development. The members of this receptor family are TRKA, TRKB and TRKC and they are encoded by the genes NTRK1, NTRK2 and NTRK3. Alterations of NTRK genes can induce carcinogenesis both in neurogenic and non-neurogenic cells. The prevalence of NTRK gene fusion is under 1% in solid tumors, but is highly encountered in rare tumors. The presence of NTRK 1 gene fusion is associated, in some types of neoplasia, with a favorable evolution, but the presence of NTRK 2 may be associated with a poor prognosis. The identification of cancer patients harboring NTRK gene fusions is constantly growing, especially with the advent of NTRK inhibitors. This has promisingly provided a rationale for personalized therapeutics that improved outcomes in settings with this signature.

The Role of Programmed Cell Death Receptor 1 in Lung Cancer.

BACKGROUND/AIM: Lung cancer is the most common cancer worldwide. Cancer immunotherapy is the activation of the immune system against cancer. The latest method of immunotherapy involves immune checkpoint inhibitors. Increased levels of programmed death ligand 1 (PD-L1) expression were observed on non-small-cell lung cancer. The association between PD-L1 expression and clinicopathological characteristics in lung cancer is still unclear. PATIENTS AND METHODS: This is a cross-sectional, observational study that evaluated a sample of 41 lung cancer patients diagnosed between March 2019 and December 2020. PD-L1 tumor expression is described as a percentage. RESULTS: Patients were diagnosed with non-microcellular lung cancer and aged 37 to 87 years. Most patients were diagnosed with adenocarcinoma. According to the analysis, the average age of patients with negative PD-L1 tumors was 65.6 years, and of those with positive PD-L1 tumors was 63.6 years. The average value of the tumor proportion score for males was 26.97%, and for females 25.55%. CONCLUSION: No correlation was found between PD-L1 tumor expression and the age and sex of patients.

Systematic review of the role of indocyanine green near-infrared fluorescence in safe laparoscopic cholecystectomy (Review).

With the widespread introduction of laparoscopic cholecystectomy, the incidence of iatrogenic main bile duct lesions has significantly increased, with incidences ranging from 0.2 to 1.5% according to current studies. Although there are studies regarding the use of indocyanine green (ICG) for improved visualization of the biliary anatomy, there is no consensus on the dose, timing and optimal mode of administration, or the indications in which ICG provides a real benefit through increased safety in laparoscopic cholecystectomy (LC). A systematic review was performed on articles in English published until March 2021, which were identified on PubMed, Springer Nature, Elsevier and Scopus via specific mesh terms: 'Indocyanine green'/'near-infrared fluorescence' and 'laparoscopic cholecystitis'. The most used method of administration of ICG was intravenously, only one study evaluated the efficiency of a near-infrared cholangiogram (NIRC) when ICG was administered directly in the gallbladder. The majority of the studies included in the review used 2.5 mg of ICG administered within 1 h before imaging. The intensity of the NIRC fluorescence signal was revealed to depend on several factors, with obesity and inflammation as the most clinically significant. NIRC was reported to be a simple, feasible, safe and cost-effective procedure, which may improve safety in difficult cases of LC. NIRC use in combination with white light has been demonstrated to be superior to white light alone in identifying extrahepatic biliary anatomy, thus decreasing the risk of intraoperative bile duct injuries (BDI). For its large-scale use, data on a higher number of patients to confirm its clinical value and specific indications is required.

A Warning Call for Fertility Preservation Methods for Women Undergoing Gonadotoxic Cancer Treatment.

Malignant hematological conditions have recognized an increased incidence and require aggressive treatments. Targeted chemotherapy, accompanied or not by radiotherapy, raises the chance of defeating the disease, yet cancer protocols often associate long-term gonadal consequences, for instance, diminished or damaged ovarian reserve. The negative effect is directly proportional to the types, doses, time of administration of chemotherapy, and irradiation. Additionally, follicle damage depends on characteristics of the disease and patient, such as age, concomitant diseases, previous gynecological conditions, and ovarian reserve. Patients should be adequately informed when proceeding to gonadotoxic therapies; hence, fertility preservation should be eventually regarded as a first-intention procedure. This procedure is most beneficial when performed before the onset of cancer treatment, with the recommendation for embryos or oocytes' cryopreservation. If not feasible or acceptable, several options can be available during or after the cancer treatment. Although not approved by medical practice, promising results after in vitro studies increase the chances of future patients to protect their fertility. This review aims to emphasize the mechanism of action and impact of chemotherapy, especially the one proven to be gonadotoxic, upon ovarian reserve and future fertility. Reduced fertility or infertility, as long-term consequences of chemotherapy and, particularly, following bone marrow transplantation, is often associated with a negative impact of recovery, social and personal life, as well as highly decreased quality of life.

Maternal-Fetal Outcomes in Women with Endometriosis and Shared Pathogenic Mechanisms.

The connection between endometriosis and pregnancy outcomes is trending among the research topics. Until recently, endometriosis and its painful symptomatology were considered to be alleviated by pregnancy. However, these beliefs have shifted, as emerging literature has demonstrated the role of this condition in affecting pregnancy evolution. The underlying pathogenesis of endometriosis is still poorly understood, all the more when pregnancy complications are involved. Debatable opinions on endometriosis associated with obstetric complications exist because of the potential bias resulting from the heterogeneity of preceding evidence. This review aims to evaluate the connection between endometriosis and adverse pregnancy outcomes and their shared pathogenic mechanisms. We searched PubMed and EMBASE and focused on the studies that include placenta praevia, premature rupture of membranes, spontaneous preterm birth, gestational hypertension, preeclampsia, obstetric hemorrhages (ante- and postpartum bleeding, abruptio placentae), miscarriage, stillbirth, neonatal death, gestational diabetes mellitus, gestational cholestasis, small for gestational age, and their association with endometriosis. Not only the risks of emergence were highlighted, but also the pathogenic connections. Epigenetic alterations of some genes were found to be mirrored both in endometriosis and obstetric complications. This review issues a warning for providing increased attention to pregnant women with endometriosis and newborns as higher risks of preeclampsia, placental issues, and preterm deliveries are associated.

COVID-19 Mid-term Impact on Hepatocellular Carcinoma in Patients With Hepatitis C Chronic Infection.

BACKGROUND/AIM: Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. PATIENTS AND METHODS: We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. RESULTS: Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. CONCLUSION: Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.

Modulation of Immune System - Strategy in the Treatment of Breast Cancer.

BACKGROUND/AIM: In women, breast cancer is the most commonly diagnosed cancer type and at the same time the main cause of cancer-related death. Many mechanisms are involved in the tumor microenvironment to restrict the anti-tumor activity by the immune system. Identification of novel prognostic tools based on immunological data could make significant impact in developing innovative immunotherapy strategies that will restore the anti-tumor immune system efficacy. PATIENTS AND METHODS: The study was performed on patients diagnosed with breast cancer, who were divided into two groups depending on the expression of HER2. For the studied group, first we described the infiltrate inflammatory on slides stained with haematoxylin eosin (HE) and in the second part we used flow cytometry in order to measure the percentage of T lymphocytes from the peripheral blood before and after breast cancer treatment. RESULTS: High presence of tumor-infiltrating lymphocytes (TILs) was associated with prognostic improvement, better disease-free survival, distant disease-free survival and overall survival. In breast cancer, the presence of TILs predicts the full pathological response rate (pCR) after neoadjuvant chemotherapy. TILs are one of the best examples of the strict relationship existing between natural defence and carcinogenesis. CONCLUSION: Modulation of the immune system is a promising strategy in the treatment of breast cancer, especially in triple-negative and HER2-positive molecular subtypes, the most immunogenic subtypes with a poor prognosis.

Hypocalcemia: A possible risk factor for anastomotic leak in digestive surgery.

Anastomotic leaks (ALs) remain the most severe complication in digestive surgery, as well as the most consumptive in terms of human and financial resources. There is an abundance of international research which has focused on identifying and correcting risk factors, and on individualized surgical management as well. The most frequent risk factors are male sex, obesity, diabetes, advanced malignant disease, ASA score, perioperative blood loss or perioperative transfusion, long operation time, emergency operation and altered nutritional status. The aim of the present study was to measure the preoperative serum calcium level and to find a possible correlation between calcium levels and the risk of AL occurrence. A retrospective analysis of medical records for 122 patients who underwent surgical gut resection with anastomosis for different pathologies was carried out. Preoperative serum calcium level and the occurrence of AL was noted. The results revealed that the average value of total blood calcium was 8.78 mg/dl, without a significant difference in sex groups. Hypocalcemia was identified in 44 patients (36.1%). AL was identified in 8 patients (6.6%), with a statistically insignificant difference between male and female patients. The average value of blood calcium in the AL patient group was 8.07 mg/dl, while in patients without AL the average value was 8.83 mg/dl. Hypocalcemia, defined as a serum calcium level below 8.5 mg/dl, was observed in 7 of the 8 patients presenting with AL (87.5%) and 37 patients who did not present with AL (32.5%), a significant difference with which to consider and include hypocalcemia in the group of risk factors for AL (P=0.001). In conclusion, preoperative low serum calcium level can represent a risk factor for AL in digestive surgery.

Lung Cancer, Covid-19 Infections and Chemotherapy.

BACKGROUND/AIM: The Covid-19 epidemic has severely strained health care systems across the globe. The impacts are multiple especially for patients cared for cancer. The Covid-19 epidemic has several impacts on the management of lung cancer patients. The aim of this work was to summarize the available epidemiological data on patients diagnosed with lung cancer infected with Covid-19 and describe the different strategies to improve the management of these patients by summarizing the recommendations in this area. PATIENTS AND METHODS: The Teravolt cohort is an observational multicenter registry, including patients with non-small cell cancer, small cell cancer or mesothelioma but also epithelial tumors and a diagnosis of Covid-19. The Theravolt registry indicates an unexpectedly high mortality rate in patients with thoracic malignancies with COVID-19. RESULTS: Between March 26 and April 12, 2020, 200 patients treated in 8 countries were included. They had a performance status (PS) of 0-1 in 72% of cases, were smokers or ex-smokers in 81% of cases, had non-small cell cancer (76% of cases), were under treatment in 74% of cases, and the majority were first-line cases (57%). The hospitalization rate was 76% and the mortality rate 33%; only 10% of patients with criteria for intensive care hospitalization were admitted to the intensive care. CONCLUSION: Data presented in this registry suggest a high mortality in patients with thoracic cancer and Covid-19. Therofere, the importance to create a safe healthcare system during Covid-19 pandemic is underlined along with the need for essential effective clinical service delivery to patients with lung cancer.

Umbilical hernia masking primary umbilical endometriosis - a case report.

Endometriosis is a gynecologic condition affecting mainly the pelvic organs. However, extrapelvic endometriosis has been reported in almost all parts of the body. Umbilical endometriosis, either primary or secondary, is uncommon and has a documented neoplastic risk. We present the case of a 46-year-old woman with a large umbilical hernia associating primary umbilical endometriosis discovered during surgery and confirmed later by pathological and immunohistochemical exams. The patient underwent omphalectomy and partial omentum resection, alongside with mesh abdominal wall repair. The patient was informed about the recurrence risk and was asymptomatic at follow-up consults.

A Rare Cause of Bowel Obstruction: Peritoneal Metastases in Osteosarcoma at the Tibia in a Young Female Patient with Brain Metastasis. Case Report.

Osteosarcomas are the most frequent primary malignant bone tumors in children and adolescents. Like brain metastases in osteosarcomas, the bowel metastases are very rare. We present the case of a 23-year-old female patient, diagnosed and operated in 2008 of osteosarcoma at the tibia, for which she had sessions of neoadjuvant and adjuvant chemotherapy, but presented lungs metastases for which she underwent surgery in 2014. Then, in March 2015, she was diagnosed with an intracranial expansive process, an osteosarcoma metastasis, for which a total ablation of the tumor was performed during the early postoperatory period, being transferred to the General Surgery Clinic for abdominal pain, abdominal distention, vomiting, and lack of intestinal transit regarding faeces and intestinal gas. Both clinically and imagistically, the diagnosis was of bowel obstruction. This was the reason for performing surgery, thus discovering a bowel obstruction secondary to a metastasis of the terminal ileum and liver metastases that were confirmed as osteosarcoma metastases from an anatomopathological and immunohistochemical point of view. The bowel metastases and the osteosarcoma brain metastases are very rare entities and, their association, most often with young patients, is exceptional. However, bowel metastases must be taken into account as a possible cause of bowel obstruction in patients with osteosarcoma.