Limitation in monitoring depth of anesthesia: a case report.

Although we describe a clinical situation that most likely occurs in hundreds of operatory rooms in the world, we report this case as provocation. It concerns an unexpected awakening from an appropriate depth of anesthesia, although the BIS monitor showed a BIS index of less than 50 for a prolonged period before and after the event. Approximately 30 min after induction of anesthesia, the patient had a hypothetic sudden arousal of consciousness, with spontaneous movements, facial muscle activation, intolerance to the tracheal tube, and tearing. After immediate intravenous administration of midazolam (4 mg), the patient returned to a depth of anesthesia status, and surgery was completed uneventfully. The patient had no recall of the event when questioned during the episode, at emergence, or at 24 h, 36 h, and 7 days after surgery. Were these events spinal reflexes to pain or stimulation although the cortex was still anesthetized? Maybe this is the more rational explanation. Was the patient awake but not aware? Is it possible that our patient experienced only a transient arousal from consciousness, and that he did not have recall because the arousal time was short and we blocked memory consolidation? The latter hypothesis provides an opportunity to discuss the evidence that at the moment there is no device to assess the depth of anesthesia. We also focus on the possibility of interfering with memory processing under anesthesia.

The role of HOTAIR in the modulation of resistance to anticancer therapy.

Leading anti-tumour therapeutic strategies typically involve surgery and radiotherapy for locally advanced (non-metastatic) cancers, while hormone therapy, chemotherapy, and molecular targeted therapy are the current treatment options for metastatic cancer. Despite the initially high sensitivity rate to anticancer therapies, a large number of patients develop resistance, leading to a poor prognosis. The mechanisms related to drug resistance are highly complex, and long non-coding RNAs appear to play a crucial role in these processes. Among these, the lncRNA homeobox transcript antisense intergenic RNA (HOTAIR), widely implicated in cancer initiation and progression, likewise plays a significant role in anticancer drug resistance. It can modulate cell activities such as proliferation, apoptosis, hypoxia, autophagy, as well as epithelial-mesenchymal transition, thereby contributing to the development of resistant tumour cells. In this manuscript, we describe different mechanisms of antitumor drug resistance in which HOTAIR is involved and suggest its potential as a therapeutic predictive biomarker for the management of cancer patients.

Endocrine nuclear receptors and long non­coding RNAs reciprocal regulation in cancer (Review).

Nuclear receptors (NRs) are transcriptional regulators involved in different aspects of normal cell physiology. Their deregulation is associated with aberrant expression, gene mutations and/or epigenetic alterations that can be related to the pathogenesis of various human diseases, and especially in cancer. In particular, a complex genomic network involved in the development and progression of NR­mediated cancer has been highlighted. Advanced genomic technologies have made it possible to understand that the expression of any particular NR in a given cancer subtype is only one component of a larger transcriptional machinery that is controlled by multiple associated NRs and transcription factors. Additionally, their ability to regulate and to be regulated by molecules of non­coding RNAs, microRNAs as well as long non­coding RNAs, is opening new scenarios for understanding the role of NRs in cancer initiation and progression. In the present review, the authors aimed to outline the reciprocal interactions that exist between the main NRs and long non­coding RNAs in different tumor diseases, to suggest new diagnostic biomarkers as well as therapeutic strategies for these tumors.

Improving the quality of patient care in lung cancer: key factors for successful multidisciplinary team working.

International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals "in the same room", who collectively decide upon the best possible treatment. However, this is not a panacea for cancer treatment. The impact of multidisciplinary care (MDC) on patient outcomes is not univocal, while the effective functioning of the MDT depends on many factors. This review presents the available MDT literature with an emphasis on the key factors that characterize high-quality patient care in lung cancer. The study was conducted with a bibliographic search using different electronic databases (PubMed Central, Scopus, Google Scholar, and Google) referring to multidisciplinary cancer care settings. Many key elements appear consolidated, while others emerge as prevalent and actual, especially those related to visible barriers which work across geographic, organizational, and disciplinary boundaries. MDTs must be sustained by strategic management, structured within the entity, and cannot be managed as a separate care process. Furthermore, they need to coordinate with other teams (within and outside the organization) and join with the broad range of services delivered by multiple providers at various points of the cancer journey or within the system, with the vision of integrated care.

Risk Management Activities in a Lung Cancer Multidisciplinary Team at a Comprehensive Cancer Center: Results of a Prospective Analysis.

PURPOSE: The objective of the study was to highlight sources of harm that could negatively affect the lung cancer multidisciplinary team (MDT) activities to reduce the level of risk of each factor. METHODS: A modified Delphi approach was used by a board of multi-health care professionals of the lung cancer MDT to identify the main processes, subprocesses, and risk factors of the multidisciplinary pathway of patients with lung cancer. A semiquantitative matrix was built with a five-point scale for probability of harm (likelihood) and severity of harm (consequences) according to the international risk management standards (ISO 31000-2018). The risk level was calculated by multiplying likelihood × consequences. Mitigation strategies have been identified and applied by the MDT to reduce risks to acceptable levels. RESULTS: Three main processes (outpatient specialist visit, MDT discussion, and MDT program implementation), eight related subprocesses, and 16 risk factors were identified. Four risk factors (25%) were related to outpatient specialist visit, seven (43.75%) to case discussion, and five (31.25%) to program implementation. Overall, two risk factors were assigned a low-risk level (12.5%), 11 a moderate-risk level (68.75%), one (6.25%) a high-risk level, and two (12.5%) a very high-risk level. After the implementation of mitigation measures, the new semiquantitative risk analysis showed a reduction in almost all hazardous situations: two risk factors (12.5%) were given a very low level, six (37.5%) a low level, seven (43.75%) a moderate level, and one (6.25%) a very high level. CONCLUSION: An interdisciplinary risk assessment analysis is applicable to MDT activities by using an ad hoc risk matrix: if the hazard is identified and monitored, the risk could be reduced and managed in a short time.

Bibliometric Network Analysis on Rapid-Onset Opioids for Breakthrough Cancer Pain Treatment.

BACKGROUND AND OBJECTIVES: Proper breakthrough cancer pain (BTcP) management is of pivotal importance. Although rapid-acting, oral and nasal transmucosal, fentanyl formulations (rapid-onset opioids, ROOs) are licensed for BTcP treatment, not all guidelines recommend their use. Presumably, some research gaps need to be bridged to produce solid evidence. We present a bibliometric network analysis on ROOs for BTcP treatment. METHODS: Documents were retrieved from the Web of Science (WOS) online database. The string was "rapid onset opioids" or "transmucosal fentanyl" and "breakthrough cancer pain". Year of publication, journal metrics (impact factor and quartile), title, document type, topic, and clinical setting (in-patients, outpatients, and palliative care) were extracted. The software tool VOSviewer (version 1.6.17) was used to analyze the semantic network analyzes, bibliographic coupling, journals analysis, and research networks. RESULTS: 502 articles were found in WOS. A declining trend in published articles from 2014 to 2021 was observed. Approximately 50% of documents regard top quartile (Q1) journals. Most articles focused on ROOs efficacy, but abuse and misuse issues are poorly addressed. With respect to article type, we calculated 132 clinical investigations. The semantic network analysis found interconnections between the terms "breakthrough cancer pain," "opioids," and "cancers." The top co-cited article was published in 2000 and addressed pain assessment. The largest number of partnerships regarded the United States, Italy, and England. CONCLUSION: In this research area, most articles are published in top-ranked journals. Nevertheless, paramount topics should be better addressed, and the implementation of research networks is needed.

A multicenter randomized phase 4 trial comparing sodium picosulphate plus magnesium citrate vs. polyethylene glycol plus ascorbic acid for bowel preparation before colonoscopy. The PRECOL trial.

Background: Adequate bowel preparation before colonoscopy is crucial. Unfortunately, 25% of colonoscopies have inadequate bowel cleansing. From a patient perspective, bowel preparation is the main obstacle to colonoscopy. Several low-volume bowel preparations have been formulated to provide more tolerable purgative solutions without loss of efficacy. Objectives: Investigate efficacy, safety, and tolerability of Sodium Picosulphate plus Magnesium Citrate (SPMC) vs. Polyethylene Glycol plus Ascorbic Acid (PEG-ASC) solutions in patients undergoing diagnostic colonoscopy. Materials and methods: In this phase 4, randomized, multicenter, two-arm trial, adult outpatients received either SPMC or PEG-ASC for bowel preparation before colonoscopy. The primary aims were quality of bowel cleansing (primary endpoint scored according to Boston Bowel Preparation Scale) and patient acceptance (measured with six visual analogue scales). The study was open for treatment assignment and blinded for primary endpoint assessment. This was done independently with videotaped colonoscopies reviewed by two endoscopists unaware of study arms. A sample size of 525 patients was calculated to recognize a difference of 10% in the proportion of successes between the arms with a two-sided alpha error of 0.05 and 90% statistical power. Results: Overall 550 subjects (279 assigned to PEG-ASC and 271 assigned to SPMC) represented the analysis population. There was no statistically significant difference in success rate according to BBPS: 94.4% with PEG-ASC and 95.7% with SPMC (P = 0.49). Acceptance and willing to repeat colonoscopy were significantly better for SPMC with all the scales. Compliance was less than full in 6.6 and 9.9% of cases with PEG-ASC and SPMC, respectively (P = 0.17). Nausea and meteorism were significantly more bothersome with PEG-ASC than SPMC. There were no serious adverse events in either group. Conclusion: SPMC and PEG-ASC are not different in terms of efficacy, but SPMC is better tolerated than PEG-ASC. SPMC could be an alternative to low-volume PEG based purgative solutions for bowel preparation. Clinical trial registration: [ClinicalTrials.gov], Identifier [NCT01649674 and EudraCT 2011-000587-10].

Advantages and issues of concern regarding approaches to peripheral nerve block for total hip arthroplasty.

In older patients with comorbidities, hip fractures are both an important and debilitating condition. Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improving clinical outcomes, the choice of the most effective and safest pathway represents a great challenge. A key point of concern is the anesthetic approach and above all the choice of the locoregional anesthesia combined with general or neuraxial anesthesia.

Postoperative Chylothorax.

Chylothorax is an unusual but serious complication of thoracic surgical procedures, and may carry considerable morbidity if not addressed in a timely fashion. Thoracic surgeons should be able to promptly diagnose this complication, and understand the implications of prolonged chyle loss to the patient. Conservative measures are often successful; direct intervention with percutaneous embolization of the cisterna chyli or thoracoscopic ligation is reserved for refractory cases. Some controversy exists regarding the timing of reintervention to limit the accumulated chyle loss. Prophylactic thoracic duct ligation has been examined but to date does not seem to reduce the incidence of chylothorax.

A pilot prospective randomized, controlled trial comparing LigaSure™ tissue fusion technology with the ForceTriad™ energy platform to the electrosurgical pencil on rates of atrial fibrillation after pulmonary lobectomy and mediastinal lymphadenectomy.

OBJECTIVES: The use of bipolar sealing devices during pulmonary resection is particularly useful in thoracoscopic surgery. Theoretically, a bipolar device, which contains the current in a smaller area and completes the current cycle only through the tissue between the electrodes, may reduce the proportion of patients experiencing atrial fibrillation compared with monopolar devices such as the electrosurgical pencil using which the current completes the cycle through the patient. We investigated the impact of the LigaSure™ (LS) tissue fusion technology with the ForceTriad™ energy platform device on the incidence of postoperative atrial fibrillation and on the reduction of postoperative chest tube output and hospital length of stay after open pulmonary lobectomy. METHODS: A pilot prospective randomized, controlled trial comparing LS tissue fusion technology with the ForceTriad™ energy platform to the conventional electrosurgical pencil. Overall, 146 patients with resectable lung cancer were recruited at the Division of Thoracic Surgery of the Istituto Nazionale Tumori, Fondazione Pascale, IRCCS, between January 2011 and July 2013. Of these, 119 candidates to open lobectomy for non-small-cell lung cancer were randomized to either LS tissue fusion technology with the ForceTriad™ energy platform (LS: 57 patients) or standard haemostatic procedure (standard treatment, ST: 62 patients) for hilar and mediastinal nodal dissection. The primary end-point was to compare the incidence of postoperative atrial fibrillation of LS compared with ST. The secondary end-point was to compare the efficacy of LS compared with ST in terms of total chest tube drainage, daily chest tube drainage and chest tube duration. RESULTS: There was no statistically significant difference between LS and ST in terms of postoperative atrial fibrillation (P=0.31). However, LS was associated to significant reduction of duration of both mediastinal nodal dissection (P=0.017) and the cumulative chest tube drainage (P=0.025). CONCLUSIONS: The incidence of atrial fibrillation with LS tissue fusion technology with the ForceTriad™ energy platform is not reduced as compared with conventional electrosurgical pencil. However, the use of LS during mediastinal nodal dissection is associated to shorter duration of lymphadenectomy and duration of chest tube drainage.

Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer.

The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery.

High-intensity training and cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease and non-small-cell lung cancer undergoing lobectomy.

OBJECTIVES: Peak VO2, as measure of physical performance is central to a correct preoperative evaluation in patients with both non-small-cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) because it is closely related both to operability criteria and the rate of postoperative complications. Strategies to improve peak VO2, as a preoperative pulmonary rehabilitation programme (PRP), should be considered favourably in these patients. In order to clarify the role of pulmonary rehabilitation, we have evaluated the effects of 3-week preoperative high-intensity training on physical performance and respiratory function in a group of patients with both NSCLC and COPD who underwent lobectomy. METHODS: We studied 40 patients with both NSCLC and COPD, age < 75 years, TNM stages I-II, who underwent lobectomy. Patients were randomly divided into two groups (R and S): Group R underwent an intensive preoperative PRP, while Group S underwent only lobectomy. We evaluated peak VO2 in all patients at Time 0 (T0), after PRP/before surgery in Group R/S (T1) and 60 days after surgery, respectively, in both groups (T2). RESULTS: There was no difference between groups in peak VO2 at T0, while a significant difference was observed both at T1 and T2. In Group R, peak VO2 improves significantly from T0 to T1: 14.9 ± 2.3-17.8 ± 2.1 ml/kg/min ± standard deviation (SD), P < 0.001 (64.5 ± 16.5-76.1 ± 14.9% predicted ± SD, P < 0.05) and deteriorates from T1 to T2: 17.8 ± 2.1-15.1 ± 2.4, P < 0.001 (76.1 ± 14.9-64.6 ± 15.5, P < 0.05), reverting to a similar value to that at T0, while in Group S peak VO2 did not change from T0 to T1 and significantly deteriorates from T1 to T2: 14.5 ± 1.2-11.4 ± 1.2 ml/kg/min ± SD, P < 0.00001 (60.6 ± 8.4-47.4 ± 6.9% predicted ± SD, P < 0.00001). CONCLUSIONS: PRP was a valid preoperative strategy to improve physical performance in patients with both NSCLC and COPD and this advantage was also maintained after surgery.

Endoscopic surveillance for hereditary non-polyposis colorectal cancer (HNPCC) family members in a Southern Italian region.

BACKGROUND: Surveillance in hereditary non-polyposis colorectal cancer (HNPCC) family members recommends baseline colonoscopy starting at age 20 and then surveillance colonoscopy every 1-2 years. AIMS: To verify adherence to the guidelines for HNPCC family members enrolled in endoscopic surveillance. METHODS: Data regarding 11 HNPCC families was retrieved from our database. Excluding 11 probands, 106 family members were evaluated and 40 underwent surveillance. RESULTS: At baseline colonoscopy, 7 colorectal cancers (CRC), 14 polyps (PO) [1 inflammatory, 2 hyperplastic, 10 adenomas with low grade dysplasia (LGD-AD) and 1 adenoma with high-grade dysplasia (HGD-AD)] were diagnosed in sixteen individuals. Twenty-eight HNPCC family members underwent endoscopic surveillance, with a total of 94 surveillance colonoscopies. Of these, 45 were positive (4 CRC, 3 inflammatory PO, 34 hyperplastic PO, 21 LGD-AD and 5 HGD-AD). Mean time between two consecutive surveillance colonoscopies was 24.6 months (range 4-168). Median time to first positive surveillance colonoscopy was 84 months for HNPCC family members with negative baseline colonoscopy, and 60 months for those with positive baseline colonoscopy (p=0.21). CONCLUSIONS: Our data suggests that surveillance colonoscopy every 2 years is adequate to diagnose advanced lesions in HNPCC family members, and improves their compliance with surveillance.