Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial.

BACKGROUND: Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. STUDY DESIGN: Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0-100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. RESULTS: Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90-100] vs 100 [90-100]; P=.077) and 14 days thereafter (Likert scale 100 [80-100] vs 100 [90-100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70-1.83] vs 1.58 cm3 [1.08-2.69], respectively; P<.001), less intraoperative blood loss (Δhemoglobin, 0.2 g/dL [-0.1 to 0.4] vs 0.5 g/dL [0.2-0.9]; P<.001), and higher satisfaction after 14 days (100 [90-100] vs 100 [80-100]; P=.026), whereas surgeon preference favored general anesthesia (90 [79-100] vs 100 [90-100], respectively; P=.001). All other secondary outcomes did not differ between groups (resection margin status R1, 6.6% vs 2.1% [P=.26]; cone fragmentation, 12.1% vs 6.3% [P=.27]; procedure duration, 151.5 seconds [120-219.5] vs 180 seconds [117-241.5] [P=.34]; time to complete hemostasis, 60 seconds [34-97] vs 70 seconds [48.25-122.25] [P=.08]; complication rate, 3.3% vs 1.1% [P=.59]). In a multivariate analysis, parity (P=.03), type of transformation zone (P=.03), and cone volume (P=.02) and not study group assignment, age, body mass index, and degree of dysplasia independently influenced the primary endpoint. CONCLUSION: Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for endometrial cancer-derived peritoneal metastases: a systematic review.

Cytoreductive surgery (CRS) is an appropriate treatment for selected patients with endometrial cancer (EC)-derived peritoneal metastases (PM). Hyperthermic intraperitoneal chemotherapy (HIPEC) may enhance the therapeutic efficacy of CRS in these patients. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials and case reports reporting on the safety and efficacy of CRS and HIPEC in patients with EC-derived PM. Eight publications reporting on 68 patients were identified. The mean patient age was 57.1 years and the mean time from initial treatment of EC to CRS and HIPEC was 22.3 months. 41/64 patients had adenocarcinomas, type II cancers were present in 23/64 patients. The mean peritoneal carcinomatosis index (PCI) was 16.7. A complete surgical resection CC-0 was achieved in 44/63 (70%) patients. The chemotherapy regimens used for HIPEC were variable, but all included cisplatin, administered either alone (39/68 patients) or combined with doxorubicin or paclitaxel or mitomycin (29/68 patients). The duration of HIPEC was 60 min in 51/68 patients and 90 min in 17/68 patients. Mostly, the closed technique was used (55/68 patients). Adverse events grades 1/2, 3, and 4 were observed in 23/63, 12/63, and 6/63 patients, respectively. Treatment-associated mortality was 1% (1/63). After CRS and HIPEC, most patients received systemic chemotherapy (46/63 patients). Median disease-free and overall survival ranged from 7 to 18 and 12 to 33 months, respectively. In conclusion, CRS and HIPEC in EC with PM is safe and feasible. An additional therapeutic value of HIPEC is suggested, but prospective comparative trials are warranted.

Intraperitoneal cisplatin and doxorubicin as maintenance chemotherapy for unresectable ovarian cancer: a case report.

BACKGROUND: Primary advanced, unresectable ovarian cancer (OC) is treated with palliative systemic chemotherapy. Intraperitoneal chemotherapy may be an alternative local maintenance therapy. CASE PRESENTATION: A 75 year old woman with laparoscopically and histologically confirmed unresectable OC was treated with 13 cycles of intraperitoneal cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 over 2 years using laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC). Objective tumor response (tumor regression on histology, stable disease on repeated video-laparoscopy and peritoneal carcinomatosis index) was noted. No Common Terminology Criteria for Adverse Events (CTCAE) > grade 3 were observed. EORTC QLQ-C30 quality of life measurements were stable throughout the therapy. CONCLUSIONS: Repeated intraperitoneal chemotherapy with cisplatin and doxorubicin applied as PIPAC may be an effective maintenance treatment in women with primary advanced, unresectable OC.

Biosorption of U(VI) by the green algae Chlorella vulgaris in dependence of pH value and cell activity.

Biosorption of uranium(VI) by the green alga Chlorella vulgaris was studied at varying uranium concentrations from 5 µM to 1mM, and in the environmentally relevant pH range of 4.4 to 7.0. Living cells bind in a 0.1mM uranium solution at pH 4.4 within 5 min 14.3 ± 5.5 mg U/g dry biomass and dead cells 28.3 ± 0.6 mg U/g dry biomass which corresponds to 45% and 90% of total uranium in solution, respectively. During 96 h of incubation with uranium initially living cells died off and with 26.6 ± 2.1 mg U/g dry biomass bound similar amounts of uranium compared to dead cells, binding 27.0 ± 0.7 mg U/g dry biomass. In both cases, these amounts correspond to around 85% of the initially applied uranium. Interestingly, at a lower and more environmentally relevant uranium concentration of 5 µM, living cells firstly bind with 1.3 ± 0.2 mg U/g dry biomass to 1.4 ± 0.1 mg U/g dry biomass almost all uranium within the first 5 min of incubation. But then algal cells again mobilize up to 80% of the bound uranium during ongoing incubation in the time from 48 h to 96 h. The release of metabolism related substances is suggested to cause this mobilization of uranium. As potential leachates for algal-bound uranium oxalate, citrate and ATP were tested and found to be able to mobilize more than 50% of the algal-bound uranium within 24h. Differences in complexation of uranium by active and inactive algae cells were investigated with a combination of time-resolved laser-induced fluorescence spectroscopy (TRLFS), extended X-ray absorption fine structure (EXAFS) spectroscopy and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Obtained results demonstrated an involvement of carboxylic and organic/inorganic phosphate groups in the uranium complexation with varying contributions dependent on cell status, uranium concentration and pH.

Radiometric dating of the type-site for Homo heidelbergensis at Mauer, Germany.

The Mauer mandible, holotype of Homo heidelbergensis, was found in 1907 in fluvial sands deposited by the Neckar River 10 km southeast of Heidelberg, Germany. The fossil is an important key to understanding early human occupation of Europe north of the Alps. Given the associated mammal fauna and the geological context, the find layer has been placed in the early Middle Pleistocene, but confirmatory chronometric evidence has hitherto been missing. Here we show that two independent techniques, the combined electron spin resonance/U-series method used with mammal teeth and infrared radiofluorescence applied to sand grains, date the type-site of Homo heidelbergensis at Mauer to 609 ± 40 ka. This result demonstrates that the mandible is the oldest hominin fossil reported to date from central and northern Europe and raises questions concerning the phyletic relationship of Homo heidelbergensis to more ancient populations documented from southern Europe and in Africa. We address the paleoanthropological significance of the Mauer jaw in light of this dating evidence.

Hyperbaric and normobaric reoxygenation of hypoxic rat brain slices--impact on purine nucleotides and cell viability.

Hyperbaric oxygen treatment has been suggested as able to reduce hypoxia induced neuronal damage. The aim of the study was to compare the impact of different reoxygenation strategies on early metabolical (purine nucleotide content determined by HPLC) and morphological changes (index of cell injury after celestine blue/acid fuchsin staining) of hypoxically damaged rat neocortical brain slices. For this purpose slices (300 microm and 900 microm) were subjected to either 5 or 30 min of hypoxia by gassing the incubation medium with nitrogen. During the following reoxygenation period treatment groups were administered either 100% oxygen (O) or room air (A) at normobaric (1 atm absolute, NB-O; NB-A) or hyperbaric (2.5 atm absolute, HB-O; HB-A) conditions. After 5 min of hypoxia, both HB-O and NB-O led to a complete nucleotide status restoration (ATP/ADP; GTP/GDP) in 300 microm slices. However, reoxygenation after 30 min of hypoxia was less effective, irrespective of the oxygen pressure. Furthermore, administering hyperbaric room air resulted in no significant posthypoxic nucleotide recovery. In 900 microm slices, both control incubation as well as 30 min of hypoxia resulted in significantly lower trinucleotide and higher dinucleotide levels compared to 300 microm slices. While there was no significant difference between HB-O and NB-O on the nucleotide status, morphological evaluation revealed a better recovery of the index of cell injury (profoundly injured/intact cell-ratio) in the HB-O group. Conclusively, the posthypoxic recovery of metabolical characteristics was dependent on the duration of hypoxia and slice thickness, but not on the reoxygenation pressure. A clear restorative effect on purine nucleotides was found only in early-administered HB-O as well as NB-O in contrast to room air treated slices. However, these pressure independent metabolic changes were morphologically accompanied by a significantly improved index of cell injury, indicating a possible neuroprotective role of HB-O in early posthypoxic reoxygenation.

Early biochemical and histological changes during hyperbaric or normobaric reoxygenation after in vitro ischaemia in primary corticoencephalic cell cultures of rats.

In a first series of experiments, the morphological changes of corticoencephalic cells by ischaemia were determined by staining with celestine blue-acid fuchsin in order to classify cells as intact, dark basophilic (supposedly reversibly injured) and preacidophilic or acidophilic (profoundly injured). Hypoxia and glucose-deprivation (in vitro ischaemia) markedly decreased the number of intact cells and correspondingly increased the number of both reversibly and profoundly damaged cells. The morphological characteristics indicated a partial recovery during reoxygenation either in the absence or presence of glucose and irrespective of whether normobaric or hyperbaric oxygen was used. In a second series of experiments, nucleoside triphosphate and diphosphate levels were determined in corticoencephalic cultures by high-performance liquid chromatography. Hypoxia in combination with glucose-deficiency markedly decreased the ATP:ADP, GTP:GDP and UTP:UDP ratios. A still larger fall of these ratios was observed both after normobaric and hyperbaric reoxygenation. In contrast, both normobaric and hyperbaric reoxygenation in the presence of glucose led to an almost complete recovery near the control normoxic values. In conclusion, the histological changes were not adequately reflected by changes in the nucleoside triphosphate:diphosphate ratios and, in addition, hyperbaric oxygen had neither favourable nor unfavourable effects on the early morphological and functional restitution of ischaemically damaged cells under the conditions of the present study.

Alteration of fatty acid profiles in different pulmonary surfactant phospholipids in acute respiratory distress syndrome and severe pneumonia.

Impairment of alveolar surfactant function has been documented in the acute respiratory distress syndrome (ARDS) and in severe pneumonia (PNEU); however, the underlying mechanisms are not completely understood. In the current report we present a detailed analysis of fatty acid (FA) profiles of different surfactant phospholipid (PL) classes isolated from bronchoalveolar lavage fluids (BALF) and large surfactant aggregates (LSA) from mechanically ventilated patients with ARDS (n = 8), ARDS associated with lung infection (ARDS + PNEU, n = 9), and PNEU (n = 22). Healthy volunteers served as control subjects (n = 8). PLs were isolated by thin-layer chromatography, and the FA profile of each PL class was assessed by gas chromatography. In addition, the minimal surface tension (gamma min) of untreated LSA and of LSA after supplementation with additional dipalmitoylated phosphatidylcholine (DPPC) was analyzed (pulsating bubble surfactometer). As compared with control LSA, the percentage of palmitic acid in phosphatidylcholine (PC) was significantly decreased in all patient groups (ARDS 63.0 +/- 2.0%, ARDS + PNEU 64.6 +/- 4.9%, PNEU 65.6 +/- 1.5%, control subjects 80.1 +/- 1.7%), whereas the relative amount of unsaturated species in PC increased significantly in all groups. Phosphatidylglycerol (PG) and phosphatidylinositol (PI) presented similar FA profiles in control subjects, but differed in the patients. The FA pattern of sphingomyelin (SPH) and phosphatidylethanolamine (PE) displayed only minor changes under conditions of respiratory failure. As compared with control subjects a highly significant increase of gamma min from near zero to approximately 16 mN/m was observed in all patients and was found to be inversely correlated to the percentage of palmitic acid in PC of LSA or BALF. Accordingly, values for gamma min were significantly improved upon secondary supplementation of LSA with DPPC up to control values. We conclude that marked changes in the FA composition of the predominant surfactant PL classes occur, both in ARDS triggered by nonpulmonary events and PNEU. The marked reduction of palmitic acid in the PC fraction may be related to changes in surfactant function under these conditions.

Ultrasonic nebulization for efficient delivery of surfactant in a model of acute lung injury. Impact on gas exchange.

We investigated the effect of ultrasonic nebulization versus instillation of exogenous surfactant on gas exchange abnormalities provoked by detergent inhalation in perfused rabbit lungs. Ventilation-perfusion (VA/Q) distribution was assessed by the multiple inert gas elimination technique. For nebulization of natural bovine surfactant (Alveofact), an ultrasonic device was placed in line with the inspiratory gas flow tubing, manufacturing particles with a mass median aerodynamic diameter of approximately 4.5 microM and high aerosol concentration. In vitro studies demonstrated biochemical and biophysical integrity of postnebulization surfactant. Lung aerosol deposition was monitored by a laser-photometric technique. In lungs with sham inhalation of saline, tracheal instillation of surfactant (approximately 11 mg/kg body weight, infused over 50 min) provoked substantial VA/Q mismatch and limited shunt flow, whereas lung surfactant deposition by ultrasonic nebulization (approximately 7 to 9 mg/kg body weight; nebulization time, 50 min) did not interfere with physiologic gas exchange. Tween 20 inhalation provoked severe VA/Q mismatch with predominant shunt-flow (approximately 21%). This was not reversed by "rescue" application of instilled surfactant, but largely reversed by nebulized surfactant (shunt reduced to 5.5%; p < 0.01). Analysis of postaerosol lavage fluid demonstrated partial reconstitution of surface activity by nebulized surfactant. We conclude that ultrasonic nebulization may be employed for efficient delivery of functionally intact natural surfactant to the distal bronchoalveolar space. This approach effects rapid improvement of gas exchange in a model of acute homogeneous lung injury.

Surface properties and sensitivity to protein-inhibition of a recombinant apoprotein C-based phospholipid mixture in vitro--comparison to natural surfactant.

Surfactant alterations due to protein leakage are implicated in the pathogenesis of the adult respiratory distress syndrome. In the present study, surface properties of a palmitic acid containing phospholipid mixture (DPPC: PG: PA/68.5:22.5:9) supplemented with 2% recombinant human surfactant apoprotein C (PLM-Crec) were compared to those of the lipids alone (PLM) and to those of calf lung surfactant extract (CLSE). Experiments were performed in a Wilhelmy balance and in a pulsating bubble surfactometer. Adsorption facilities and dynamic surface tension-lowering properties of the surfactants alone, their sensitivity to the inhibitory effect of fibrinogen (fbg), and their capacity to restore surface properties of fbg-inhibited CLSE were investigated. PLM revealed limited surface activity, was very sensitive to inhibition by fbg and had moderate effect on the surface properties of fbg-inhibited CLSE. In contrast, PLM-Crec and CLSE revealed similar excellent adsorption kinetics and dynamic surface tension lowering properties. Higher percentage of SP-C within the synthetic mixture (up to 10%) or additional admixture of human purified or recombinant SP-A (up to 10%) did not further improve these surface properties. However, PLM-Crec was markedly more sensitive to inactivation by fbg than CLSE. The surface activity of fbg-inhibited CLSE was fully restored by additional admixture of CLSE or PLM-Crec in both the Wilhelmy and the bubble system, with slight superiority of the natural surfactant extract. We conclude that the surface properties of PLM-Crec are clearly superior to those of the apoprotein-free lipid mixture and are similar to those of the natural surfactant extract CLSE. PLM-Crec is markedly more sensitive to inhibition by fibrinogen than CLSE, but possesses nearly equivalent efficacy in restoring the surface properties of fbg-inhibited CLSE as compared to the natural material.