Prognostic significance of BRCA1 and BRCA2 methylation status in circulating cell-free DNA of Pancreatic Cancer patients.

Introduction: Pancreatic cancer is the most fatal cancer type in the world. Its high mortality is mostly correlated to the absence of symptoms and the difficulty in early diagnosis, which in the majority of the cases occurs when the disease has already spread metastasis. Nowadays, tests that could predict early diagnosis are not available yet and the number of prognostic tests is limited. Hence, there is an urgent need for biomarkers capable of detecting early development or the rapid progression of the disease. Patients and Methods: DNA methylation represents the most frequent epigenetic event among tumor suppressor genes that are involved in various carcinogenic pathways. In the recent study we have tried to evaluate, for the first time, the prognostic value of BRCA1 and BRCA2 methylation in the cell-free DNA of pancreatic cancer patients. Using methylation-specific real-time PCR we examined the methylation status of BRCA1 and BRCA2 in 55 patients with operable and 50 patients with metastatic pancreatic cancer. In the operable disease setting, BRCA1 was found to be methylated in 33/55 (63.5%) patients examined while BRCA2 was also highly methylated in 31/55 (56.3%). In the metastatic disease, BRCA1 was found to be methylated in 26/50 (52%) while BRCA2 was found methylated in 23/50 (46%). Results: All control samples were negative for BRCA1 orBRCA2 promoter methylation. Patients with operable pancreatic cancer and a methylated BRCA1 and BRCA2 promoter status had a statistically significant poorer outcome as compared with patients with a non-methylated one (p=0.012 and p=0.001, respectively). Conclusion: In this study plasma methylation of BRCA1 and BRCA2 represents a frequent event in both the operable as well as in the metastatic setting. BRCA1 and BRCA2 methylation was significant and correlated with decreased survival in patients with operable pancreatic cancer. A larger cohort of patients is required to further explore the potential of these findings as well as to investigate whether BRCA1/2 methylation in plasma could serve as a potential prognostic biomarker in pancreatic cancer.

Simultaneous Resection for Colorectal and Liver Metastases, new equipment and personalized medicine.

Nowadays we perform synchronous colorectal cancer resection along with synchronous liver metastases. We investigated whether colon resection first is safer than liver resection first and if simultaneous surgeries are in general safe. Patients and Methods: Twenty patients were included in our multicenter study. In our study patients had simultaneous laparoscopic resection of primary colorectal cancer and liver metastases. The patients included were divided into two groups based on their first surgery. Group A had colon resection first (n = 10) and group B had liver resection first (n = 10). All adverse effects and outcomes were compared after the first day of hospitalization. Results: The only difference between the two groups was the operative blood loss. It was observed to be less in group B. Conclusion: In our study we did not observe any significant difference regarding the order of the operation.

Ablation for Single Pulmonary Nodules, Primary or Metastatic. Εndobronchial Ablation Systems or Percutaneous.

Single pulmonary nodules are a difficult to diagnose imagining artifact. Currently novel diagnostic tools such as Radial-EBUS with or not C-ARM flouroscopy, electromagnetic navigation systems, robotic bronchoscopy and cone beam-compuer tomography (CBCT) can assist in the optimal guidance of biopsy equipment. After diagnosis of lung cancer or metastatic disease as pulmonary nodule, then surgery or ablation methods as local treatment can be applied. The percutaneous ablation systems under computed tomography guidance with radiofrequency, microwave, cryo and thermosphere have been used for several years. In the past 10 years extensive research has been made for endobronchial ablation systems and methods. We will present and comment on the two different ablation methods and present up to date data.

The Effectiveness of Metabolic Bariatric Surgery in Preventing Gynecologic Cancer - from Pathophysiology to Clinical Outcomes.

Obesity and cancer represent two pandemics of current civilization, the progression of which has followed parallel trajectories. To time, thirteen types of malignancies have been recognized as obesity-related cancers, including breast (in postmenopausal women), endometrial, and ovarian cancer. Pathophysiologic mechanisms that connect the two entities include insulin resistance, adipokine imbalance, increased peripheral aromatization and estrogen levels, tissue hypoxia, and disrupted immunity in the cellular milieu. Beyond the connection of obesity to carcinogenesis at a molecular and cellular level, clinicians should always be cognizant of the fact that obesity might have secondary impacts on the diagnosis and treatment of gynecologic cancer, including limited access to effective screening programs, resistance to chemotherapy and targeted therapies, persisting lymphedema, etc. Metabolic bariatric surgery represents an attractive intervention not only for decreasing the risk of carcinogenesis in high-risk women living with obesity but most importantly as a measure to improve disease-specific and overall survival in patients with diagnosed obesity-related gynecologic malignancies. The present narrative review summarizes current evidence on the underlying pathophysiologic mechanisms, the clinical data, and the potential applications of metabolic bariatric surgery in all types of gynecologic cancer, including breast, endometrial, ovarian, cervical, vulvar, and vaginal.

Probiotics in Postoperative Pain Management.

Postoperative pain is the unpleasant sensory and emotional experience after surgery, its origin being both the inflammatory reaction induced by the surgical trauma on the abdominal wall and the splanchnic pain induced by the activation of nociceptors of the viscera, which are highly sensitive to distension, ischemia, and inflammation. Nowadays, it is well recognized that there is a close relationship between the gut microbiome and pain perception, and that microbiome is highly affected by both anesthesia and surgical manipulation. Thus, efforts to restore the disturbed microbiome via supplementation with beneficial bacteria, namely probiotics, seem to be effective. In this article, the knowledge gained mainly from experimental research on this topic is analyzed, the concluding message being that each probiotic strain works in its own way towards pain relief.

Inguinal Lymph Node Metastasis as Sole Manifestation of Ovarian / Fallopian Tube Cancer: a Review of the Literature.

Background: Ovarian/fallopian tube cancer is the deadliest gynecological malignancy. Most cases are diagnosed at an advanced stage, typically after the cancer has spread to the peritoneal cavity, or via lymphatic drainage. The presence of distant lymph node metastasis in the inguinal region is a rare manifestation of lymphatic metastasis. Since the 2014 FIGO staging revision, ovarian cancer patients with inguinal metastasis are classified as stage IVB. However, the clinical significance of such an upstaging remains under investigation. Materials and Methods: Both Scopus and PubMed / MEDLINE databases were utilized, by inputting the following combination of keywords: (Ovarian cancer OR Fallopian tube cancer) AND (Inguinal lymph node AND Metastasis) on June 31st, 2023. The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. Results: Twelve patients from equal number of case reports were included in our review. Mean age of diagnosis was 56,5 years old, with 3 out of 12 women to be premenopausal at the time of diagnosis. Regarding the histologic type, 67% (8 out of 12) of the cases were serous adenocarcinoma and 4 patients (33%) were diagnosed with fallopian tube malignancy. All patients, except one, were treated with primary cytoreductive surgery. In all patients optimal cytoreductive surgery was achieved. All patients, except one, received adjuvant chemotherapy. Regarding the disease-free survival, mean DFS is calculated approximately at 2 years (23,1 months). Conclusion: Inguinal lymph node metastases from ovarian / fallopian tube malignancy as initial site of metastasis is extremely rare. However, patients with inguinal masses should be investigated for ovarian / fallopian malignancy. Further investigation ought to be conducted to enlighten the pathway and the oncological significance of inguinal lymph node metastasis in ovarian cancer patients.

Endobronchial Radiofrequency Ablation for pulmonary nodules with Radial-Ebus and Navigation: Pros and Cons.

Introduction: Pulmonary nodules are common in the everyday clinical practice. There is always a diagnostic issue with this imaging finding. Based on the size we can use a variety of imaging and diagnostic techniques. Moreover; in the case of primary lung cancer or metastasis we can use radiofrequency ablation endobronchially. Patients and Methods: We used the radial-endobronchial ultrasound with C-arm and Archemedes, Bronchus electromagnetic navigation in order to acquire biopsy sample and we also used rapid on-site evaluation as a rapid diagnosis for pulmonary nodules. After rapid diagnosis we used the radiofrequency ablation catheter in order to ablate central pulmonary nodules. Results: Both techniques provide efficient navigation, however, with the Bronchus system less time is needed. The new radiofrequency ablation catheter provides efficient results in central lesions with low watts ≤40. Conclusion: We provided in our research a protocol to diagnose and treat such lesions. Future larger studies will provide more data on this subject.

Laparoscopic Surgery with Concomitant Hernia Repair and Cholecystectomy: An Alternative Approach to Everyday Practice.

INTRODUCTION: Concomitant surgeries have been performed previously in several centers with experience in laparoscopic surgeries. These surgeries are performed in one patient under one operation with anesthesia. METHODS: We performed a retrospective unicenter study from October 2021 to December 2021 analyzing patients who underwent laparoscopic hiatal hernia repair with cholecystectomy. We extracted data from 20 patients who underwent hiatal hernia repair together with cholecystectomy. Grouping of data by hiatal hernia type showed 6 type IV hernias (complex hernia), 13 type III hernias (mixed type) and 1 type I hernia (sliding hernia). Out of the 20 cases analyzed, 19 were patients suffering from chronic cholecystitis and 1 patient presented with acute cholecystitis. The average operating time was 179 min. Minimum blood loss was achieved. Cruroraphy was performed in all cases, mesh reinforcement was added in five cases, and fundoplication was performed in all cases, with 3 Toupet, 2 Dor and 15 floppy Nissen fundoplication procedures performed. Fundopexy was routinely performed in cases of Toupet fundoplication. A total of 1 bipolar and 19 retrograde cholecystectomies were performed. RESULTS: All patients had favorable postoperative hospitalization. Patient follow-up took place at 1 month, 3 months and 6 months, with no sign of recurrence of hiatal hernia (anatomical or symptomatic) and no symptoms of postcholecystectomy syndrome. In two patients, we had to perform colostomy. CONCLUSION: Concomitant laparoscopic hiatal hernia repair and cholecystectomy is safe and feasible.

Corrigendum to "Tentative study on radial endobronchial ultrasonography evaluating airway wall thickness before and after bronchial thermoplasty" [Respir. Med. Case Rep. 36 (2022) 101571].

[This corrects the article DOI: 10.1016/j.rmcr.2021.101571.].

Cryo-Biopsy versus 19G needle versus 22G needle with EBUS-TBNA endoscopy.

Introduction: We have been using cryo-biopsy for endobronchial lesions for lung cancer diagnosis and debulking. Cryo-biopsy is also known to be an excellent tool for diagnosis of lung interstitial disease. Recently cryo-biopsy with the 1.1mm probe was used for lymphnode biopsy. Patients and Methods: 311 patients participated with lymphadenopathy and at least one lung lesion. The following tools were used for diagnosis; 22G Mediglobe Sonotip, 22G Medigolbe, 21G Olympus, 19G Olympus and 1.1mm cryo probe ERBE CRYO 2 system (3 seconds froze). A PENTAX Convex-probe EBUS was used for biopsy guidance. Results: Cell-blocks slices had a higher number in the 19G needle group (19G> Cryo Probe>22G Mediglobe Sonotip >21G Olympus >22G Mediglobe). Conclusion: Cryo biopsy of the lymphnodes is safe with the 1.1mm cryo probe. Further studies are needed in order to evaluate new probes and the technique specifications.

"One Shot" Sample Evaluation of 22G, 22G upgraded, 21G and 19G needle for Endobronchial Ultrasound-EBUS-TBNA.

Background: There are still diagnostic issues with lung cancer and mediastinum lymphadenopathy. Endobronchial ultrasound (EBUS) is a state of the art equipment for the diagnosis of lymphadenopathy and central lesions. Objective: To investigate the sample size with one pass. Patients and Methods: 248 Stage IV patients were included in our study. All patients had a CT of the thorax with either lymphadenopathy or lyphadenopathy plus pulmonary lesions. Patients had a biopsy with endobronchial ultrasound with 22G Mediglope, 22G Mediglope Sonotip, 21G Olympus and 19G Olympus needle. We collected information regarding the cancer type, cell block, tissue, age, sex, lesion size and needle type. Results: The cancer type diagnosis was associated with the needle diameter. The number of cell-blocks were associated with the lesion size and needle diameter. Slices from the tissue and cell-blocks were again associated with the lesion size and needle diameter. Conclusion: One pass is enough for cancer diagnosis, however; careful selection has to be made among patients regarding the needle diameter. In the case of lymphoma suspicion we should use 19G needle.

Mesothelioma: A Case in a Diagnostic Timeline and the Efficiency of Robot-Assisted Surgery.

We present a case of a 65-year-old male with a difficulty to diagnose mesothelioma. To be specific, three attempts were made to diagnose the disease, and only with a large sample performed with robot-assisted surgery, our pathologists were able to identify the malignancy. The novelty for our case is mostly based on the timeline of the diagnosis along with the tissue samples where we present the course of the transformation from benign to malignancy. All tissue biopsies were checked by two independent pathologists. Conclusively, diagnosis for small local lesions should be performed with an endoscopic method, video-assisted or robot-assisted.

Factors Affecting the Nuclei in Newborn and Children.

It is known that children are more sensitive to the effects of medical treatments and environment than adults. Today there is limited information regarding the differences in genotoxic effects in children. The micronucleus assay is a method that is used to monitor genotoxicity, and it was validated several years before. Today there is international interest for exfoliated buccal cells. Most of the micronuclei studies in children have been performed with the analyses of lymphocytes. However, there is vast interest in using exfoliated cells from the oral cavity. The reason is that other type of cells are acquired non-invasively, this is an important issue in paediatric cohorts. Unfortunately a limitation of measuring micronuclei frequency is that it has been observed to be low in newborns and on the other hand there are a large number of patients and cell sample counts. It has been observed that radiation exposure and environmental pollutants increase the micronuclei frequency in newborn and children. Regarding the medical treatments, there is little data and several studies are needed to optimise the doses. There is the need to observe if there is a relationship between micronuclei in lymphocytes and exfoliated cells and to identify the baseline of the micronuclei levels. Moreover, we evaluate the changes in response to the toxic agents. Prospective cohorts studies will clarify the predictive value of micronuclei for cancer and chronic diseases for both children and adults. Novel molecular technologies will assist in the elucidation of different biological pathways and molecular mechanisms connected with the micronulcei levels in newborn and children.

Radial Endobronchial Ultrasound for Lung Cancer Diagnosis: Tips and Tricks.

Introduction: Endoscopic techniques have been upgraded in the recent 10 years. We can use the radial endobronchial ultrasound to reach distal nodules in the periphery of the lungs, but also we can use it in order to make biopsies in lesions without endobronchial findings. Patients and Methods: We included in our study 248 patients with pulmonary nodules up to 4 cm. We use a radial endobronchial system from FUJI, a PENTAX bronchoscope and a C-ARM. We recorded the cancer type, biopsy method, time of each procedure, cell blocks and slices from cell blocks. Results: Two thirds of patients belonged to males (61.7%), forceps was the main tissue extraction technique (118, 47.6%) and tumors sized 1 to 2 cm were the most encountered (96, 38.7%). Samples with tissue content were present in 175 patients (70.6%) and one cell block dominated in the samples (109, 43.9%). Less than 20 minutes were needed to complete the operative procedure for the half patients (127, 51.2%), the C-Arm implementation concerned 117 persons (47.2%) and the majority of tumors was located in the central area of the lungs (178, 71.8%). Less time was necessary for central lesions and larger biopsy samples were acquired without the extensive use of C-ARM. Conclusion: The larger the nodule ≥2cm and in periphery the less we use the C-ARM and the time of the procedure is between 20-40 minutes. Moreover; we have more tissue sample and cell block slices.

The 3-D configuration of excisional skin wound healing after topical probiotic application.

Nowadays, there is an increasing knowledge that probiotic bacteria, topically applied, affects skin pathology. The objective of this study is to evaluate the effect on wound healing of locally applied probiotics by calculating the 3-D configuration of a standardized excisional wound. Fifty-two male Wistar rats were randomly allocated into groups: control, PRO1 [L. plantarum] and PRO2 [L. rhamnosus, B. longum]. Six excisional full-thickness wounds were created on each dorsum by an 8-mm circular biopsy punch; probiotics or saline were applied on days 0, 2, 4, 8, 16, photos of the wounds taken and specimens excised for histology [4 rats/group/time-point]. Both probiotic-groups exhibited accelerated healing significantly faster than the control, throughout, PRO2 exhibiting finally the best results [day 16]. However, only on day 2, did PRO1 exhibit the best results [wounded area, borders distance and epitheliazation line]. The results clearly demonstrate that the topical application of probiotics significantly improves the healing process, each strain working differently and more effectively in different healing phases. Thus, a combined formula containing different probiotics to modulate various healing phases is desirable. To this end our research continous.

Perianal fistulas: A review with emphasis on preoperative imaging.

PURPOSE: We aim to present a comprehensive literature review which focuses on the preoperative imaging of perianal fistulas. MATERIAL/METHODS: Pelvic magnetic resonance imaging (MRI) and endoanal ultrasound (EAUS) are the two first-line imaging modalities for the preoperative evaluation of patients with perianal fistulas. We conducted a search in PubMed, Scopus and Google Scholar concerning articles comparing pelvic MRI with EAUS, which were published from 1994 until 2019. RESULTS: In most articles, pelvic MRI is superior to EAUS for the evaluation of perianal fistulas (especially for supralevator and extrasphincteric ones). Preoperative pelvic MRI is associated with statistically significant better results and prognosis after surgical treatment of the disease. Preoperative EAUS poses high sensitivity and specificity in identifying intersphincteric and transsphincteric perianal fistulas, as well as the internal opening of a fistula-in-ano. There is only one meta-analysis which compares the diagnostic accuracy of the two mentioned imaging modalities in preoperative fistula detection. Sensitivity of both - pelvic MRI and EAUS, is acceptably high (0.87). Specificity of pelvic MRI is 0.69 in comparison to EAUS (0.43), but both values are considered low. CONCLUSIONS: Future well-designed prospective studies are needed to investigate the diagnostic accuracy of pelvic MRI and EAUS in the preoperative assessment of patients with perianal fistulas. Moreover, the combination of pelvic MRI and EAUS should also be studied, since several published articles suggest that it could lead to improved diagnostic accuracy. A novel treatment algorithm for perianal fistulas could arise from this study.

Airway local endoscopic pharmacological treatment; current applications and future concepts.

INTRODUCTION: Local treatment of the airways and lung parenchyma has been used in clinical practice for several years for a variety of diseases. METHODS: A variety of endoscopic tools for local treatment exist, especially for treating malignancies. Using these endoscopic tools, one can administer drugs specifically designed for the airways. DISCUSSION: This article presents all locally administered treatment options and provides useful insights for future local endoscopically applied treatments.

Tentative study on radial endobronchial ultrasonography evaluating airway wall thickness before and after bronchial thermoplasty.

AIM: We aimed to observe the clinical practicing value of radial endobronchial ultrasonography evaluating airway wall thickness before and after bronchial thermoplasty. METHODS: We selected two patients who received bronchial thermoplasty in our hospital. We measured the thickness of each segmental airway wall of each patient by radial endobronchial ultrasonography, and observed the difference before and after the therapy. All the treatments and measurement were performed by a designated bronchoscopist and the locations and depths of the ultrasound probe were relatively fixed, to reduce the operational error. RESULTS: In both two patients, the mean thicknesses of all segmental airway walls was 4.9 ± 0.7 mm before the first session of BT; the mean thickness was 4.13 ± 0.92 mm before the second session; the mean thickness was 2.69 ± 0.68 mm before the third session; the mean thickness was 2.7 ± 0.5 mm in the follow-up measurement at six months after the BT treatment; all thicknesses of airway wall were significantly reduced comparing with those before treatment; all the thicknesses of the airway walls were stable without any tendency of thickening after six months. Although the airways in the right middle lobe of both two patients were not received BT, their thicknesses were also decreased comparing with those before the treatment; both upper lobes bronchus of both two patients were not activated in the first and second sessions, but their thicknesses were also decreased at the third measurement. CONCLUSION: Radial endobronchial ultrasonography is a simple and practical method to measure the thickness of patient's airway wall. Bronchial thermoplasty can effectively reduce the thickness of airway wall. It can reduce airway smooth muscle by direct activation and other possible more complicated mechanism, which need further research.

Perinatal management of enlarged bronchogenic cyst causing hydrops fetalis.

Bronchogenic cysts are rare congenital anomalies that they are usually diagnosed prenatally during the routine second trimester scan. We present such a rare case of bronchogenic cyst in a fetus. Our initial scan demonstrated a big cystic mass, which enlarged progressively causing shifting of the mediastinum and compression of the fetal heart. Consequent hydrops fetalis was treated with thoracoamniotic shunt and the pregnancy continued with no further complications. Pontnatal period, surgery and long term follow-up was uneventful.

Tracheal fistula repair with stent placement after failure of reconstruction with muscle tissue. A lung cancer surgery complication.

A report a case of a 63 year old male diagnosed with lung cancer adenocarcinoma. The patient had a right paratracheal mass diagnosed with EBUS-TBNA 22G. The patient had surgery, however 7 days after the billau catheter was removed pneumothorax was diagnosed which did not resolved. Bronchoscopy reveled two minor fistulas in the interior wall of the trachea. An additional surgery was performed in order to add muscle patches on the exterior part of the trachea. Unfortunately additional stent placement was placed after a silicon stent since the muscle patches failed. We chose a metallic auto expandable stent since after three months of follow up a small metastatic lesion was observed in the liver. Stent placement is an option for these patients and the right stent has to be placed for each case.