Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

EBUS-TBLC increase the diagnosis rate in different type of peripheral pulmonary lesions.

Background and objective: Recently, endobronchial ultrasonography with guide sheath-guided (EBUS-GS) has been increasingly used in the diagnosis of peripheral pulmonary lesions (PPLs) from human natural orifice. However, the diagnostic rate is still largely dependent on the location of the lesion and the probe. Here, we reported a new procedure to improve the diagnostic rate of EBUS-transbronchial lung cryobiopsy (EBUS-TBLC), which performed under general anesthesia with laryngeal mask airway (LMA) in all of the patients. This study retrospectively evaluated the diagnosis of PPLs with 'blind-ending' type (Type I) and 'pass-through' type procedures (Type II) of EBUS-GS-TBLB or EBUS-TBLC respectively. Methods: Retrospective review of 136 cases performed by EBUS-GS-TBLB or EBUS-TBLC for PPLs over 2 years. Results: A total of 126 cases EBUS-GS-TBLB or EBUS-TBLC were performed during the study period. Among them, 66 (52.4%) were performed Type I and 60 (47.6%) were performed Type II. Clinical baseline characteristics did not differ between two groups. The overall diagnosis rate of 126 patients with EBUS-GS-TBLB or EBUS-TBLC was 73% (92/126), and different method type have significant influence on the diagnostic yield (P = 0.012, x2 = 4.699). Among them, diagnostic yields for Type I with forceps biopsy (n=34), Type I with cryobiopsy (n=32), Type II with forceps biopsy (n=30), and Type II with cryobiopsy (n=30) were 72.5%, 64.5%, 70.4% and 74.2% respectively (Figure 2A). The study further compared the outcomes of different procedures in concentric and eccentric lesion. Diagnostic yields for Type I with eccentric (n=30), Type I with concentric (n=36), Type II with eccentric (n=34), and Type II with concentric (n=26) were 58.2%, 76.9%, 60.2% and 74.8%, respectively (P < 0.05). The incidence of complications in 126 patients was 2.6%. Conclusion: EBUS-GS-TBLB and EBUS-TBLC both are very safe and highly diagnostic technique; different method types have significant influence on the diagnostic yield. Moreover, Type II procedure has higher diagnostic yield. In addition, Type I with eccentric had the lowest diagnosis yield.

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.

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.

Chronic Obstructive Pulmonary Disease and Non-Small Cell Lung Cancer an association.

Objectives: Lung cancer is known to be associated with chronic obstructive pulmonary disease. Moreover; nutritional status is associated with chronic obstructive disease treatment and lung cancer. Our aim was to evaluate the interaction of the COPD status and treatment of non-small cell lung cancer. Methods: Eighty-two patients were enrolled in our multicenter study. Chronic obstructive disease stage, spirometry and treatment was recorded along with the treatment and Body Mass Index (BMI), Mediterranian Diet Score, Pack Years, Basic Metabolsim (RMR) (kcal/day), VO2 (ml/min), Ve (lt/min) and Physical Activity. The statistical analysis was performed using the JMP 14.3 (SAS Inc 2018) software. Results: The drug pairs showed a steady and unchanged by time health condition for 48 patients. Overall, 31 patients were recorded with worse COPD health conditions. The one-way ANOVA clearly indicated that chemotherapy induced the best FEV1-difference conditions with a positive effect of 8.56 mean FEV volume, the combined treatment simply did not have an effect (-0.9), while immunotherapy and patients receiving radiation decreased their FEV1 volume down to -4.23 and -5.15 mean values. Conclusions: Patients receiving chemotherapy alone had their chronic obstructive disease improved with less drugs and exacerbations, while patients receiving immunotherapy had their chronic obstructive disease stable, while all other treatment combinations worsened the patients chronic obstructive disease. Nutritional status did not affect the chronic obstructive disease of these patients in any way.

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.

Sotorasib after immune checkpoint inhibitor administration induces hepatotoxicity. True, false or just another adverse effect of NSCLC treatment.

Non-small cell lung cancer is still diagnosed at a late disease stage and systematic therapy is necessary. Currently we have three main treatment modalities; chemotherapy, targeted with tyrosine kinase inhibitors and immune check point inhibitors. In the recent years and based on new studies we can administer combination of chemotherapy and immunotherapy, or radiotherapy and immunotherapy. Every treatment approach is based on the specific gene expression of the tumor. Tyrosine kinase inhibitors have been used for more than a decade for epidermal growth factor positive tumors, the same for anaplastic lymphoma kinase and proto-oncogene 1. Programmed death-ligand 1 expression has been found to be associated with the efficiency of immune checkpoint inhibitors. However; there are still several subpopulations in non-small cell lung cancer patients. We will comment on the group with KRAS G12C mutation and the targeted therapy with sotorasib for its efficiency and toxicity based on new studies.

Immunotherapy for the elderly. Maybe the best option for lung cancer?

Lung cancer is usually diagnosed at advanced stage and systematic therapy is administered. New current diagnostic techniques such as the convex-endobronchial ultrasound, radial endobronchial ultrasound, cone beam ct, electromagnetic navigation and robotic bronchoscopy provide us with a high diagnostic yield. These techniques are minimal invasive and patients with comorbidities such as chronic obstructive pulmonary disease and heart failure can be diagnosed with minimal adverse effects. All these techniques provide sufficient sample for molecular investigation. Since immunotherapy was first administered, we have more and more information regarding the appropriate patient target group. Several published studies divided patients as elderly ≥75 and non-elderly ≤74 and investigated the adverse effects of different drugs and survival. In our current commentary we present information on patients receiving immunotherapy versus chemoimmunotherapy in two groups of elderly and non-elderly. Elderly patients can receive both combinations without differences between the two groups, however; more studies are needed to clarify certain aspects.

Epithelial Ovarian Cancer: A Five Year Review.

Ovarian cancer is a malignant disease that affects thousands of patients every year. Currently, we use surgical techniques for early-stage cancer and chemotherapy treatment combinations for advanced stage cancer. Several novel therapies are currently being investigated, with gene therapy and stem cell therapy being the corner stone of this investigation. We conducted a thorough search on PubMed and gathered up-to-date information regarding epithelial ovarian cancer therapies. We present, in the current review, all novel treatments that were investigated in this field over the past five years, with a particular focus on local treatment.

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.

Positron Emission-Computed Tomography, Cryobiopsy versus Bronchoalveolar Lavage and Computed Tomography Findings for Interstitial Lung Disease: A Long-Term Follow-Up.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.

Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

Pro-inflammatory cytokines/chemokines, TNF-α, IL-6 and MCP-1, as biomarkers for the nephro- and pneumoprotective effect of silibinin after hepatic ischemia/reperfusion: Confirmation by immunohistochemistry and qRT-PCR.

The present study investigated the potential nephro- and pneumoprotective effect of silibinin (Si) after hepatic ischemia-reperfusion (I/R) injury, by measuring pro-inflammatory factors. Sixty-three rats were randomly assigned into three groups, as follows: (a) the sham group (n = 7 rats), subjected to opening and closing the abdomen; (b) the control group (n = 28 rats), subjected to 45-min hepatic ischemia followed by reperfusion; and (c) the silibinin group (n = 28), subjected to 45-min hepatic ischemia followed by intravenous administration of lyophilised SLB-HP-ß-CD before reperfusion. Control and silibinin groups were further subdivided into time-point groups, according to the duration of reperfusion. TNF-α, IL-6 and MCP-1 expressions were determined immunohistochemically and by qrT-PCR at each time-point. Kidney TNF-α expression was significantly lower at 180 and 240 min, while lung TNF-α expression was significantly lower at 240 min. Comparison between the control and Si group at the same time-points showed very strong evidence of difference at 240 min, with the levels of IL-6 shifting towards lower values in the Si group. Finally, we found a high MCP-1 expression after 120 min. We conclude that hepatic I/R injury remotely increases pro-inflammatory mediators in the kidney and lung, whereas silibinin shows a time-dependent nephro- and pneumoprotective effect.

Reduction in Pediatric Surgery's Emergency Department Visits During COVID-19 Pandemic in a Tertiary University General Hospital in Greece.

Background From January 2020, coronavirus has caused more than three million deaths. Lockdown has been enforced in many countries worldwide, affecting the emergency department visits of many surgical specialties. Methods The purpose of this study was to present the difference in trends in pediatric emergency department visits from March 1 to May 30, 2020, compared to the same 3-month period in 2019 in a tertiary university hospital in Greece, which was one of the referral centers for COVID-19 patients. Results A 42.5% reduction in emergency department visits was observed. In 2020, only 196 patients visited the pediatric surgery emergency department, versus 341 patients in 2019 (p<0.05). The reasons for visiting the emergency department did not change in most categories. Even though visits to the emergency department were reduced, the rates of the distance of the patient's residency from the hospital remained roughly the same. Hospital admission rates remained roughly the same. Conclusion Even though there was a huge decrease in numbers, the reasons for visiting the ED remained roughly the same. The only exception was indoor accidents, which increased in 2020.

Are patients willing to be informed on the risks and complications associated with the proposed therapy? A survey on informed consent.

INTRODUCTION: Informed consent is essential to the patient-physician relationship. The paternalistic old-time approach used by physicians to achieve the optimal management is changing today; detailed medical information must be disclosed to the patients regarding their health problem. AIM: The aim of this study was to highlight the value of informed consent in the context of medical practice as well as to emphasize its importance through the prism of human rights. MATERIALS AND METHODS: A patient survey was conducted in two public and one private hospitals in Greece. Eighty-three inpatients from the Surgical Departments of Democritus University Hospital of Alexandroupolis (DUHA), Laikon University Hospital of Athens (LUHA) and a private hospital were included in the study. A questionnaire regarding patients' attitude towards informed consent was distributed to patients prior to surgery. RESULTS: The majority of the patients (63.86% in DUHA, 59.38% in LUHA, and 78.95% in the private hospital) opted for full disclosure regarding the course and development of their condition. CONCLUSION: Patients want to be informed about their treatment options and possible complications so that they can make decisions about their treatment after a comprehensive and understandable discussion.

Gallbladder perforation. A case series and review of the literature.

INTRODUCTION: Gallbladder perforation (GBP) is an uncommon life-threatening and almost exclusive complication of cholecystitis. It is often associated with relatively high morbidity and mortality rates due to delay in diagnosis. GBP still continues to be a challenging issue for the surgeons. Most cases can only be diagnosed during surgery. The aim of this retrospective, case series was to present our clinical experience with gallbladder perforation and to provide an overview of promoting factors, clinical manifestations, diagnostic workup and management of GBP on the basis of recent literature review. PATIENTS AND METHODS: This study involved four patients with gallbladder perforation (three males and one female), who were treated in our department from May 2019 to November 2019. We made a retrospective analysis of these patients and a review of the related literature. RESULTS: According to Niemeier's classification, all patients had type II gallbladder perforation. Mean age was 70 years (range 50-85 years). They had also significant comorbidities, of which diabetes mellitus was the most common (three patients). Ultrasonography was the initial mode of investigation in these four patients. Out of the four cases, three patients underwent immediate intervention and only one patient was initially managed conservatively with intravenous antibiotics. CONCLUSIONS: Early diagnosis of gallbladder perforation and immediate intervention are of crucial importance. Clinical examination, diagnostic imaging and high index of suspicion of this severe condition would be significant in establishing an early diagnosis of the perforation. KEY WORDS: Cholecystitis, Gallbladder perforation, Niemeier.

Acute pneumothorax due to immunotherapy administration in non-small cell lung cancer.

Nowadays we have novel therapies for advanced stage non-small cell lung cancer. Immunotherapy has been introduced in the market for several years and until now its administration is mostly based on the programmed death-ligand 1. First line treatment with immunotherapy can be administered alone if programmed death-ligand 1 expression is ≥ 50%. All therapies for advanced stage disease have advantages and disadvantages, immunotherapy until now has presented mild adverse effects when compared to chemotherapy. However; it is known to induce inflammatory response to different tissues within the body. In our case acute pneumothorax was induced after immunotherapy administration.

A Case of Symptomatic Gallbladder Agenesis with Chronic Abdominal Symptoms.

The anatomical area of the extrahepatic bile ducts exhibits plethora of anatomic variants. The detailed study and comprehension of anatomic variations of extrahepatic bile ducts is a prerequisite in order to avoid the intraoperative biliary or tract damages, but they are also necessary for the targeted treatment of any complications. Gallbladder agenesis is a rare congenital anomaly of the biliary tree with an estimated incidence of 0.007-0.027% in surgical series which is much lower compared to the incidence of other gallbladder anomalies. It may be asymptomatic, but sometimes is associated with symptoms such as upper quadrant abdominal pain, which may be mistaken for cholecystitis and can lead the patient to the operating room. We present a case of a 30-year-old male patient without any significant past medical history presented with a 2-year history of upper abdominal complaints, dyspepsia, epigastric abdominal pain and weight loss, normal laboratory workup and unclear radiological signs which led him to exploratory laparoscopy due to the patient's chronic symptoms, in order to exclude the presence of another underlying pathologic process. In addition to our case presentation, a relative  review of literature was conducted. As a conclusion, examinations, such as transabdominal ultrasonography, may be misleading and MCRP should be the principal method of investigation to establish a presumptive diagnosis. However, in cases with a strong suspicion for a different underlying pathology, further investigation with exploratory laparoscopy may be warranted.

Laparoscopic resection of giant adrenal malignant tumors, a case series and review of the literature.

Laparoscopic approach for suspected adrenal malignancies remains a controversial issue and it gets more controversial, when managing giant adrenal malignant tumors. The aim of this paper is to present five cases of patients with giant adrenal malignant tumors that underwent laparoscopic transabdominal lateral adrenalectomy in our department between 2010 and 2017. Literature is also reviewed in order to investigate the feasibility of laparoscopic resection in these cases.

Pleurodesis and Immunotherapy in NSCLC; Medical Thoracoscopy or VATS?

Introduction: Immunotherapy is a treatment option for non-small cell lung cancer advanced disease. However; immunotherapy in several patients induces orogonitis and effusion in different cavities. It is up to the treating physician to understand whether there is effusion due to adverse effect or disease progression. Pleurodesis in both cases might be a solution for recurrent pleura effusion. Patients and Methods: Three hundred and thirty seven non-small cell lung cancer patients with adenocarcinoma and pleura effusion during first line immunotherapy treatment underwent medical thoracoscopy or Video assisted thoracic surgery (VATS) for pleurodesis with talk poudrage. Uniportal medical thoracoscopy was performed under general with dual channel endotracheal tube in one hundred and eleven patients. Video assisted thoracic surgery was performed in one hundred and eighty seven patients and conversion from medical to VATS procedure was done to thirty nine patients. All patients had stage IV disease with pleura involvement and were under first line pembrolizumab treatment with 200mg (PD-L1 ≥ 50%). Results: The quantitative parameters of the study (expression, PY and cycle) were converted to an ordinal scale to facilitate the performance of statistical analysis. All parameters were examined as dependent against the parameter technique acting as independent to detect potential relationships. The results of multi Y versus X relationship revealed no statistically significant effect (p>0.05) of the three levels of technique against any response considered. Thus we can infer, quite safely, that the innovative operation (level 0) does not differ from the other two conventional methods (levels 2 and 3) through all parameters entered in the model. There was no significant difference between the different pleurodesis techniques. Discussion: Immunotherapy is known to induce in a number of patients pleura effusion and pericarditis. However; pleurodesis is efficient when the appropriate method is performed to every patient. Careful assessment in a case by case manner has to be performed for each patient before any procedure is performed.