Resting Physiologic Dead Space as Predictor of Postoperative Pulmonary Complications After Robotic-Assisted Lung Resection: A Pilot Study.

Lung resection surgery carries significant risks of postoperative pulmonary complications (PPC). Cardiopulmonary exercise testing (CPET) is performed to predict risk of PPC in patients with severely reduced predicted postoperative forced expiratory volume in one second (FEV1) and diffusion of carbon monoxide (DLCO). Recently, resting end-tidal partial pressure of carbon dioxide (PETCO2) has been shown as a good predictor for increased risk of PPC. However, breath-breath breathing pattern significantly affects PETCO2. Resting physiologic dead space (VD), and physiologic dead space to tidal volume ratio (VD/VT), may be a better predictor of PPC than PETCO2. The objective of this study was to prospectively determine the utility of resting measurements of VD and VD/VT in predicting PPC in patients who underwent robotic-assisted lung resection for suspected or biopsy-proven lung malignancy. Thirty-five consecutive patients were included in the study. Patients underwent preoperative pulmonary function testing, symptom-limited CPET, and a 6-min walk test. In the first 2 min prior to the exercise portion of the CPET, we obtained resting VT, minute ventilation ( V ˙ E), VD (less instrument dead space), VD/VT, PETCO2, and arterial blood gases. PPC within 90 days were recorded. Fourteen (40%) patients had one or more PPC. Patients with PPC had significantly elevated resting VD compared to those without (0.318 ± 0.028 L vs. 0.230 ± 0.017 L (± SE), p < 0.006), and a trend toward increased VD/VT (0.35 ± 0.02 vs. 0.31 ± 0.02, p = 0.051). Area under the receiver operating characteristic (ROC) for VD was 0.81 (p < 0.002), VD/VT was 0.68 (p = 0.077), and PETCO2 was 0.52 (p = 0.840). Peak V ˙ O2, V ˙ E/ V ˙ CO2 slope, pulmonary function tests, 6-min walk distance and arterial blood gases were similar between the two groups. Intensive care unit and total hospital length of stay was significantly longer in those with PPC. In conclusion, preoperative resting VD was significantly elevated in patients with PPC. The observed increase in resting VD may be a potentially useful predictor of PPC in patients undergoing robotic-assisted lung resection surgery for suspected or biopsy-proven lung malignancy. A large prospective study is needed for confirmation.

Nanosuspension coated multiparticulates for controlled delivery of albendazole.

OBJECTIVE: Improving solubility and bioavailability of albendazole (ALB). SIGNIFICANCE: ALB is a broad-spectrum anthelminthic BCS class II drug with aqueous solubility of solubility of 4.1 mg/l at 25 °C and oral bioavailability of <5%. METHODS: ALB nanosuspensions (NSs) were prepared by evaporative antisolvent precipitation using tocopherol polyethylene glycol succinate (TPGS) and polyvinyl pyrrolidone (PVP) as stabilizers and characterized for particle size, polydispersity index, and zeta potential. 32 factorial design was used to investigate effect of stabilizer concentration and speed of stirring on particle size. Concentration of TPGS was varied from 0.03 to 0.05% w/v and PVP K-30 was constant at 0.04% w/v. Stirring speed range was 1000-3000 rpm. Optimized NS was loaded on Espheres and coated with Eudragit S10& L100 and studied for friability, surface morphology and release kinetics. RESULTS: Factorial experiments revealed pronounced effect of TPGS on particle size. Optimized batch had particle size of 251 ± 7.2 nm and zeta potential -16.2 ± 2.68 mV. Saturation solubility showed increase of 16-fold in water whereas in phosphate buffer increase was fourfold. ALB-NS secondary coated Espheres released 94.3% drug in 10 h whereas ALB-MS (microsuspension) coated Espheres showed 58% release. A 1.3-fold increase in AUC0-10h was evident. Permeation from ALB-NS coated Espheres was 32% in 60 min while for ALB-MS coated Espheres it was 20%. Permeation increase occurred due to presence of TPGS which acts as a permeation enhancer.

Pulmonary tumor thrombotic microangiopathy: a systematic review.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted a systematic review of currently published and available cases of PTTM by searching the term "pulmonary tumor thrombotic microangiopathy" on the Pubmed.gov database. Seventy-nine publications were included consisting of 160 unique cases of PTTM. The most commonly reported malignancy was gastric adenocarcinoma (94 cases, 59%). Cough and dyspnea were reported in 61 (85%) and 102 (94%) cases, respectively. Hypoxemia was reported in 96 cases (95%). Elevation in D-dimer was noted in 36 cases (95%), presence of anemia in 32 cases (84%), and thrombocytopenia in 30 cases (77%). Common findings on chest computed tomography (CT) included ground-glass opacities (GGO) in 28 cases (82%) and nodules in 24 cases (86%). PH on echocardiography was noted in 59 cases (89%) with an average right ventricular systolic pressure of 71 mmHg. Common features of PTTM that are reported across the published literature include presence of dyspnea and cough, hypoxemia, with abnormal CT findings of GGO, nodules, and mediastinal/hilar lymphadenopathy, and PH. PTTM is a universally fatal disease process and this analysis provides a detailed examination of all the available published data that may help clinicians establish an earlier diagnosis of PTTM.

Insights on pulmonary tumor thrombotic microangiopathy: a seven-patient case series.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a disease process wherein tumor cells are thought to embolize to the pulmonary circulation causing pulmonary hypertension (PH) and death from right heart failure. Presented herein are clinical, laboratory, radiographic, and histologic features across seven cases of PTTM. Highlighted in this publication are also involvement of pulmonary venules and clinical features distinguishing PTTM from clinical mimics. We conducted a retrospective chart review of seven cases of PTTM from hospitals in the greater Los Angeles metropolitan area. Patients in this series exhibited: symptoms of cough and progressive dyspnea; PH and/or heart failure on physical exam; laboratory abnormalities of anemia, thrombocytopenia, elevated LDH, and elevated D-dimer; chest computed tomography (CT) showing diffuse septal thickening, mediastinal and hilar lymphadenopathy and nodules; elevated pulmonary artery pressures on transthoracic echocardiogram and/or right heart catheterization; and presence of malignancy. Tumor emboli and fibrocellular intimal proliferation were seen in pulmonary arterioles, while two patients had pulmonary venopathy. PTTM is a devastating disease occurring in patients with metastatic carcinoma. An early diagnosis is challenging. Understanding the clinical presentation of PTTM and distinguishing PTTM from clinical mimics may help achieve an early diagnosis and allow time for initiation of treatment.

Pulmonary Tumor Thrombotic Microangiopathy: Clinical, Radiologic, and Histologic Correlation.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a clinicopathologic disease entity in which the tumor cells embolize to the pulmonary vasculature leading to a series of maladaptive reactions including the activation of coagulation and fibrocellular intimal thickening. The resultant stenosis of blood vessels leads to pulmonary hypertension and eventual death from cor pulmonale. In this report, we present a case of PTTM presenting as the initial manifestation of metastatic gastric carcinoma in a young man. Although unusual in its occurrence as the initial manifestation of gastric carcinoma, the case is illustrative in its clinical, radiological and histological presentation.

Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: a dosimetric feasibility study.

INTRODUCTION: The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT). METHODS AND MATERIALS: Treatment plans were generated for five hemispheric high-grade gliomas, five hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for late effects (BED(late effects)) was generated for limbic circuit, hippocampus and NSC. Per cent relative reduction in mean physical dose and BED was calculated for each plan (standard vs. sparing). RESULTS: We were able to reduce physical dose and BED(late effects) to these critical structures by 23.5-56.8% and 23.6-66%, respectively. CONCLUSION: It is possible to spare contralateral limbic circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem low-grade gliomas. This approach may reduce late cognitive sequelae of cranial radiotherapy.

Sparing of the neural stem cell compartment during whole-brain radiation therapy: a dosimetric study using helical tomotherapy.

PURPOSE: To assess the feasibility of dosimetrically sparing the hippocampus and neural stem cell (NSC) compartment during whole-brain radiotherapy (WBRT) and prophylactic cranial irradiation (PCI). METHODS AND MATERIALS: We contoured the brain/brainstem on fused magnetic resonance /computed tomography images as the planning target volume (PTV) in 10 patients, excluding the hippocampus and NSC compartment as organs at risk. PCI and WBRT helical tomotherapy plans were prepared for each patient, with 1.0-cm field width, a pitch of 0.285, and a modulation factor of 2.5. We attempted to maximally spare the hippocampus and NSC compartment while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with a V(100) of ≥95%. Plan quality was assessed by calculating mean dose, equivalent uniform dose (EUD), and biologically equivalent dose (BED) for organs at risk and the percent volume of the PTV receiving the prescribed dose of V(100). RESULTS: In the PCI plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.5 Gy/13.1 Gy/15.7 Gy(2) (BED assuming alpha/beta ratio of 2Gy) and 11.5 Gy/13.1 Gy/12.3 Gy(10) (BED assuming alpha/beta ratio of 10Gy), respectively. In the WBRT plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.8 Gy/14.8 Gy/16.8 Gy(2) and 11.8 Gy/14.8 Gy/12.8 Gy(10), respectively. The mean V(95) for the rest of the brain (PTV) was 96.9% for both the PCI and WBRT plans. Mean PCI and WBRT treatment times were 15.93 min (range, 14.28 min-17.50 min) and 20.18 min (range, 18.43 min-22.32 min), respectively. CONCLUSIONS: It is dosimetrically feasible to spare the hippocampus and NSC compartment using helical tomotherapy during the administration of whole-brain irradiation.