Evolution of the elderly surgical oncologic patient. Case Analysis

Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania Regional Institute of Oncology, Iași, Romania, The 5th International Congress of the Society of Anesthesiology and Reanimatology of the Republic of Moldova, 16th Edition of the International Course of Guidelines and Protocols in Anesthesia, Intensive Care and Emergency Medicine, 28th Meeting of the European Society for Computing and Technology in Anesthesia and Intensive Care, September 27-29, 2018, Chisinau, the Republic of MoldovaIntroduction: The old (≥65 years) patient is common in modern surgery and implies complex challenges regarding the perioperative management and outcome. Objective: The analysis of epidemiological and outcome data in old oncologic patients submitted to surgery. Method: The retrospective observational study included all old oncologic patients submitted to surgery between 1.01-31.12.2017 in IRO Iași. Recorded parameters: age, data about cancer (organ, stage), co-morbidities, ASA score, data about surgery (organ, type, minor/major, duration), type of anesthesia, ICU lenght of stay, complications and outcome. Statistical analysis was performed with SPSS and MEDCALC. Results: The study group included 971 patients ≥65 years, which represent 23% of all oncological patients submitted to surgery during 2017 in IRO Iași. 67% pts were between 65-74 years. 498 pts (51%) had digestive cancer. 577 pts (60%) were ASA III. 939 pts (97%) had general anesthesia. In 502 pts (81%) surgery was performed with the intent to cure. In 268 pts (26%) total resection of single/multiple organs was performed. Mean duration of surgery was 127(10-450) minutes. 35 pts (4%) needed postoperative mechanical ventilation. The most frequent postoperative complication was renal failure (80 pts, 8.2%). 6 patients (0.6%) died. Conclusions: The old oncologic patient is frequently submitted to major, long-lasting surgery with the intent to cure. The constant application of multiple strategies in order to optimize the perioperative course results in low postoperative complications and mortality

Retrospective evaluation of anaemia and transfusion rate in lower abdominal oncological surgery

Grigore T. Popa University of Medicine and Pharmacy, România, Iași, Regional Institute of Oncology, Anaesthesia and Intensive Care Department, România, Iași, The 5th International Congress of the Society of Anesthesiology and Reanimatology of the Republic of Moldova, 16th Edition of the International Course of Guidelines and Protocols in Anesthesia, Intensive Care and Emergency Medicine, 28th Meeting of the European Society for Computing and Technology in Anesthesia and Intensive Care, September 27-29, 2018, Chisinau, the Republic of MoldovaBackground: Anemia is currently considered a contraindication to elective surgery, requiring diagnostic investigations and preoperative iron administration. In the oncological patient, severe anemia can increase tumor aggression and blood transfusion can induce immunosuppression, favouring cancer recurrence and metastatic rate. Objectives: To evaluate the prevalence of anemia and the perioperative transfusion rate in major abdominal-pelvic oncology surgery. Material and methods: Data of all consecutive surgical patients admitted to the ICU during 01-07.2017 were retrospectively analyzed. Patients with major lower digestive, gynecological and urological surgery were selected. Investigated parameters were - demographic data, hemoglobin (preoperative Hb1, postoperative Hb2, at dischargeHb3), anemia prevalence and perioperative transfusion rate. Statistical analysis used t-student, chi-square and ANOVA from SPSS 17. Results: Of a total 1284 patients, n = 546 patients undergoing lower abdominal surgery were enrolled in the study, mean age 60.9 (+/- 12.6) years. The mean hemoglobin Hb1/Hb2/Hb3 values were 12.4/10.6/10.5g/dL. The prevalence of anemia was 38.5% (n = 210) preoperatively, 85.9% (n = 469) postoperatively and 86.9% (n = 474) at discharge. The transfusion rate was 16.6% (n = 91), transfusion index = 2. Comparative analysis showed a higher prevalence of preoperative anemia (50.5vs21.8%, p <0.001) and transfusion rate (21.8vs 1.6%, p <0.01) in lower abdominal versus uro- gynecologic surgery. Conclusions: The analysis of surgical oncology patients with lower abdominal interventions identified an increased prevalence of anemia in all perioperative stages. Acknowledgments – The database used in this study was created by the Patient Blood Management Romanian Group for the internal audit on the prevalence of anemia and transfusion

Hyperoxia influences cancer growth and metastasis. A pilot experimental model

Grigore T. Popa University of Medicine and Pharmacy, Iași, România, Regional Institute of Oncology, Anaesthesia and Intensive Care Department, Iași, România, Regional Institute of Oncology, Department of Molecular Biology, TRANSCEND, Iași, România, CEMEX Research Center, Grigore T. Popa University of Medicine and Pharmacy, Iași, România, The 5th International Congress of the Society of Anesthesiology and Reanimatology of the Republic of Moldova, 16th Edition of the International Course of Guidelines and Protocols in Anesthesia, Intensive Care and Emergency Medicine, 28th Meeting of the European Society for Computing and Technology in Anesthesia and Intensive Care September 27-29, 2018, Chisinau, the Republic of MoldovaIntroduction: Perioperative care of cancer patients is under scrutiny. Among many factors promoting cancer recurrence and metastasis, high oxygen concentration exposure is underevaluated. While oxygen toxicity is documented in several circumstances, its implication in tumor cell growth and progression is poorly understood. Objective: To characterize high oxygen concentration exposure effects on tumor progression using a breast cancer murine model. Material and methods: A highly aggressive breast tumor cell line 4T1 (ATCC®) was injected in mammary gland in 8 week old females BALB/c mice. We divided the animals into 3 groups, each including 6 individuals: G1 – tumor bearing mice with no intervention post inoculation; G2 – primary tumor removal at 2 weeks post inoculation; G3 - primary tumor removal at 2 weeks post inoculation followed by 6 hours of 75% oxygen exposure. In all groups cancer evolution was assessed at 6 weeks by standard pathomorphological evaluation: specimens from the primary tumor, locally recurrent tumor and target organ metastasis were assessed by hematoxylin-eosin staining, and digital microscopy. Results: Surgically removed primary tumors in G3 group had similar characteristics with those in G2 group and previously described models. At study endpoint, compared with both G2 and G1 groups, G3 animals showed significantly higher tumor burden: larger local recurrence and more metastasis (larger number and dimensions) in liver and lungs, associated with significantly enlarged spleen. Conclusions: Short term (6 hours) high oxygen (75%) concentration exposure results in significantly more aggressive progression of a 4T1-BALB/c murine breast cancer model

Effects of different sevoflurane concentrations on Akt isoforms in normal and cancer breast cells. An experimental model

Grigore T. Popa University of Medicine and Pharmacy, Iași, România, Regional Institute of Oncology, Anaesthesia and Intensive Care Department, Iași, România, Regional Institute of Oncology, Department of Molecular Biology, TRANSCEND, Iași, România,The 5th International Congress of the Society of Anesthesiology and Reanimatology of the Republic of Moldova, 16th Edition of the International Course of Guidelines and Protocols in Anesthesia, Intensive Care and Emergency Medicine, 28th Meeting of the European Society for Computing and Technology in Anesthesia and Intensive Care September 27-29, 2018, Chisinau, the Republic of MoldovaIntroduction: Multiple perioperative factors influence cancer patient evolution and outcome. Microenvironmental factors activate different gene programs that enable tumor cell to invade, survive and promote drug resistance and metastasis. The effects of anesthetic drugs on cancer progression is under scrutiny, but published data are controversial and the involved mechanisms unclear. Tumor development implies PI3K/AKT pathway activation. Akt isoforms (1,2,3) are frequently amplified in various malignant tumors and associated with malignant cell survival, proliferation and invasion. Their activation is often observed in human cancers and is associated with decreased survival rate. Objective: Identification of Akt isoforms activated in sevoflurane exposed breast tumor cells. Material and methods: Normal breast cells MCF10A (ATCC®) and breast cancer cells MDA-MB-231 (ATCC®) were cultured 2D (standard adhesive culture plastic plates) and 3D (matrigel). Study groups were exposed to different sevoflurane concentrations (0.5, 2, 3, 4 mM) compared to control unexposed groups. Unexposed and sevoflurane exposed cells (2D and 3D) were evaluated by optic microscopy and viability tests. Akt isoforms were assessed by immunofluorescence. Results: Sevoflurane alters tumor cell proliferation and Akt isoforms expression in a dose-dependent manner. The phenotype of 3D 2mM sevoflurane exposed cells show an increased migration capacity which indicates increased aggressivity. Conclusions: Sevoflurane exposure of breast cancer cells influences cell proliferation, phenotype and Akt isoform expression. Increased sevoflurane concentrations activate different Akt isoforms, putatively related to epithelial-mesenchimal transition and promote cancer cell invasion, migration and metastasis

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients-A Prospective Multicenter Study (IROI Study)

To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. Prospective observational study. Fifteen ICUs worldwide. Consecutive adult ICU patients with a bladder catheter. None. Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28-and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were-associated with the development of intraabdominal hypertension during the first week in the ICU. In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28-and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1474535542NIGMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [U54 GM104940

Preoperative Cognitive Impairment and the Prevalence of Postoperative Delirium in Elderly Cancer Patients—A Prospective Observational Study

Preoperative cognitive impairment (PCI) in cancer patients includes a broad spectrum of neurocognitive changes produced by complex interplay of patient, tumoural and treatment-related factors. Reduced preoperative cognitive reserve can favour the emergence of postoperative delirium (POD). The study aims to document PCI prevalence and to assess the relationship with POD in elderly cancer patients. The prospective observational study included consecutive patients scheduled for elective surgery; PCI was assessed with Mini-Cog test and defined at a score ≤ 3, POD was screened using Nursing Delirium Screening Scale (Nu-DESC) and defined at a score ≥ 2. Data on education, American Society of Anesthesiologists (ASA) score, preoperative medications, substance use, comorbidities, sensorial deficits, surgery and anaesthesia type, anaesthetic drugs, Mini-Cog score, postoperative pain, Nu-DESC were collected. In total, 131 patients were enrolled, mean age 72.1 ± 5.9 years. PCI prevalence was 51.9% (n = 68). POD prevalence was 19.8% (n = 26), with significantly higher value in PCI patients (27.9% vs. 11.1%, p = 0.016). In multivariate analysis, Mini-Cog score ≤ 3 (OR = 2.6, p = 0.027), clock draw (OR: 2.9, p = 0.013), preoperative renal dysfunction (OR = 2.6, p = 0.012), morphine (OR = 2.7, p = 0.007), metoclopramide (OR = 6.6, p = 0.006), and high pain score (OR = 1.8, p = 0.018) had a significant association with POD development. In this sample of elderly patients, PCI had a high prevalence and predicted the emergence of POD. Incorporating Mini-Cog test into the preoperative evaluation of onco-geriatric patients seems valuable and feasible

Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms

Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT)

Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression—Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1&alpha;, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated

Tehničke poteškoće i proceduralne komplikacije zatvaranja malignih ezofagusnih respiracijskih fistula

The aim of the study was to outline technical difficulties and procedural complications of using partially covered esophageal self-expandable metal stents (SEMSs) in malignant esophageal respiratory fistulas (ERFs) as a palliative treatment option. In this study, 150 patients with malignant dysphagia underwent treatment with SEMSs. A total of 36 ERFs were detected through endoscopic or clinical assessment. Complete fistula sealing with SEMSs was possible in 35 of the 36 patients. The majority of fistulas were diagnosed in male patients with advanced esophageal cancer. All of them presented with prolonged dysphagia and cachexia. Stent migration or tumoral overgrowth was identified in 6 cases with recurrent dysphagia, and required a second stent insertion. SEMSs were highly efficient in 98% of the patients studied with ERFs, with successfully sealed ERFs after the first attempt, with an overall median survival rate of 92 days. The technique of esophageal SEMS placement is simple and can be rapidly mastered. Patients with ERFs have a respiratory shunt that makes intubation difficult and is often avoided. Restoring oral feeding increased the patient quality of life. SEMS placement is generally safe, but has few associated postoperative complications.Cilj istraživanja bio je utvrditi tehničke poteškoće i proceduralne komplikacije povezane s primjenom djelomice pokrivenih ezofagusnih samoširećih metalnih stentova (self-expandable metal stent, SEMS) kod malignih ezofagusnih respiracijskih fistula (ERF) kao opcije palijativne skrbi. U ovom istraživanju je liječenje pomoću SEMS-a primijenjeno u 150 bolesnika s malignom disfagijom. Endoskopskom ili kliničkom procjenom otkriveno je ukupno 36 ERF-a. Potpuno zatvaranje fistule pomoću SEMS-a bilo je moguće u 35 od 36 bolesnika. Većina fistula dijagnosticirana je u muškaraca s uznapredovalim rakom jednjaka. Svi su patili od dugotrajne disfagije i kaheksije. Migriranje stenta ili njegovo prerastanje tumorom utvrđeno je u 6 slučajeva opetovane disfagije i zahtijevalo je uvođenje drugog stenta. SEMS se pokazao visoko učinkovitim u 98% uključenih bolesnika s ERF-om, ERF su uspješno zatvorene u prvom pokušaju, a sveukupni medijan stope preživljenja bio je 92 dana. Tehnika postavljanja ezofagusnog SEMS-a je jednostavna i može se brzo usvojiti. U bolesnika s ERF-om respiracija je skrenuta pa je intubacija teška i često se izbjegava. Ponovno uspostavljanje hranjenja na usta poboljšava bolesnikovu kvalitetu života. Postavljanje SEMS-a uglavnom je sigurno, ali povezano s nekim poslijeoperacijskim komplikacijama

Factors Associated with Increased Risk of Urosepsis during Pregnancy and Treatment Outcomes, in a Urology Clinic

Background and Objectives: Urosepsis is a significant cause of maternal and fetal mortality. While certain risk factors for urinary tract infections (UTIs) in pregnant women are well established, those associated with an elevated risk of urosepsis in pregnant women with upper UTIs remain less defined. This study aims to identify factors linked to an increased risk of urosepsis and examine urologic treatment outcomes in such cases. Materials and Methods: We conducted a retrospective analysis on 66 pregnant women diagnosed with urosepsis over a nine-year period. A control group included 164 pregnant women with upper UTIs, excluding urosepsis, admitted during the same timeframe. This study highlights factors potentially contributing to urosepsis risk, including comorbidities like anemia, pregnancy-related hydronephrosis or secondary to reno-ureteral lithiasis, prior UTIs, coexisting urological conditions, and urologic procedures. Outcomes of urologic treatments, hospitalization duration, obstetric transfers due to fetal distress, and complications associated with double-J catheters were analyzed. Results: Pregnant women with urosepsis exhibited a higher prevalence of anemia (69.7% vs. 50.0%, p = 0.006), 2nd–3rd grade hydronephrosis (81.8% vs. 52.8%, p = 0.001), and fever over 38 °C (89.4% vs. 42.1%, p = 0.001). They also had a more intense inflammatory syndrome (leukocyte count 18,191 ± 6414 vs. 14,350 ± 3860/mmc, p = 0.001, and C-reactive protein (CRP) 142.70 ± 83.50 vs. 72.76 ± 66.37 mg/dL, p = 0.001) and higher creatinine levels (0.77 ± 0.81 vs. 0.59 ± 0.22, p = 0.017). On multivariate analysis, factors associated with increased risk for urosepsis were anemia (Odds Ratio (OR) 2.622, 95% CI 1.220–5.634), 2nd–3rd grade hydronephrosis (OR 6.581, 95% CI 2.802–15.460), and fever over 38 °C (OR 11.612, 95% CI 4.804–28.07). Regarding outcomes, the urosepsis group had a higher rate of urological maneuvers (87.9% vs. 36%, p = 0.001), a higher rate of obstetric transfers due to fetal distress (22.7% vs. 1.2%, p = 0.001), and migration of double-J catheters (6.1% vs. 0.6%, p = 0.016), but no maternal fatality was encountered. However, they experienced the same rate of total complications related to double-J catheters (19.69% vs. 12.80%, p > 0.05). The pregnant women in both groups had the infection more frequently on the right kidney, were in the second trimester and were nulliparous. Conclusions: Pregnant women at increased risk for urosepsis include those with anemia, hydronephrosis due to gestational, or reno-ureteral lithiasis, and fever over 38 °C. While the prognosis for pregnant women with urosepsis is generally favorable, urological intervention may not prevent a higher incidence of fetal distress and the need for obstetric transfers compared to pregnant women with uncomplicated upper UTIs