Perioperative intravenous lidocaine in thoracoscopic surgery for improved postoperative pain control: a randomized, placebo-controlled, double-blind, superiority trial.

Background: Pain, including associated pain management, remains a burden on patients after thoracic surgery. Our objective was to investigate whether perioperative intravenous administration of lidocaine reduces postoperative morphine consumption and pain intensity after video-assisted thoracoscopic surgery (VATS). Methods: In this double-blind, placebo-controlled superiority trial, patients undergoing VATS with a planned duration of ≤90 minutes were randomized within an intention-to-treat setting. Patients received either intravenous lidocaine or placebo as a bolus of 1.5 mg/kg 30 minutes before incision, followed by a continuous infusion of 3.0 mg/kg/hour until 2 hours after skin closure. Pain and morphine consumption were evaluated when resting and when coughing 1, 2, 4, 8, 16, 24, and 48 hours after skin closure and in a follow-up 14, 90, and 180 days postoperatively. Results: Twenty-eight patients were included in the lidocaine group, 24 in the placebo group. Patients' characteristics and preoperative pain scores were similar in both groups. When coughing, patients of the lidocaine group had less pain within 24 hours after skin closure than the placebo group (4.60±1.64 vs. 5.52±1.65; P=0.02). Morphine consumption was not statistically significantly lower in lidocaine group (18.22±12.87 vs. 21.26±9.39 mg; P=0.26). There were no significant differences between groups in secondary outcomes. Conclusions: Our results suggest that perioperative intravenous lidocaine administration reduces pain scores after VATS. The beneficial clinical effects are limited. Nevertheless, intravenous lidocaine may be helpful as part of a multimodal analgesia protocol or with patients in whom the use of other analgesics is contraindicated. Trial Registration: ClinicalTrials.gov NCT03677817.

3D-Quantitated Single Photon Emission Computed Tomography/Computed Tomography: Impact on intended Management Compared to Lung Perfusion Scan in Marginal Candidates for Pulmonary Resection.

OBJECTIVES: Based on previous studies, single-photon emission computed tomography/computed tomography (SPECT/CT) has been proven more accurate and reproducible than planar lung perfusion scintigraphy to assess lobar perfusion. However, the impact of 3D-quantitated SPECT/CT on intended management in functionally marginal candidates for pulmonary resection is unknown. The evaluation of this impact was the main aim of this study. METHODS: Consecutive candidates for lung resection underwent preoperative evaluation according to ERS/ESTS Algorithm and underwent preoperative lung perfusion imaging. The lobar contribution to the total lung perfusion was estimated using established planar scintigraphic methods and 3-dimensional quantitative SPECT/CT method (CT Pulmo3D and xSPECT-Quant, Siemens). The difference in estimated lobar perfusion with resulting changes in predicted postoperative (ppo) lung function and extent of lung resection were analyzed to reveal possible changes in operability. In-hospital outcome was assessed. RESULTS: One hundred twenty patients (46 females) were enrolled. The mean age (±SD) of patients was 68 ± 9 years, target lesions were in upper lobes in 57.7% and in lower lobes in 33.5%. The median FEV1 (forced expiratory volume in 1 second) was 70.5% (IQR 52-84) and median DLCO (diffusion capacity of lung for carbon monoxide) was 56.6% [47.1-67.4]. The planar posterior oblique method, compared to 3D-quantitated SPECT/CT, underestimated the perfusion of upper lobes by a median difference of 5% (right [2-9], left [2.5-8]; P = <.0001), while it overestimated the perfusion of lower lobes (left by 4% [2-7], right by 6% [2-9]; P = <.0001). In contrast to planar scintigraphy-based evaluation, 4 patients (3.3%), all with upper lobe lesions, were classified as inoperable when 3D-quantitated SPECT/CT was used for calculation of the ppo lung function. CONCLUSIONS: In selected patients with upper lobe lesions, 3D-quantitated SPECT/CT would have changed the treatment strategy from operable to inoperable. Importantly, postoperative mortality in this particular subgroup was disproportionally high. 3D-quantitated SPECT/CT shall be further evaluated as it might improve preoperative risk stratification in functionally marginal candidates.

CT-guided percutaneous marking of small pulmonary nodules with [99mTc]Tc-Macrosalb is very accurate and allows minimally invasive lung-sparing resection: a single-centre quality control.

PURPOSE: The detection of small lung nodules in thoracoscopic procedure is difficult when the lesions are not located within the outer border of the lung. In the case of ground-glass opacities, it is often impossible to palpate the lesion. Marking lung nodules using a radiotracer is a known technique. We analysed the accuracy and safety of the technique and the potential benefits of operating in a hybrid operating room. METHODS: 57 patients, including 33 (58%) females with a median age of 67 years (range 21-82) were included. In 27 patients, we marked and resected the lesion in a hybrid room. In 30 patients, the lesion was marked at the department of radiology the day before resection. [99mTc]Tc-Macrosalb (Pulmocis®) was used at an activity of 1 MBq in the hybrid room and at an activity of 3 MBq the day before to get technical feasible results. Radioactivity was detected using the Neoprobe® detection system. RESULTS: Precise detection and resection of the nodules was possible in 95% of the lesions and in 93% of the patients. Complete thoracoscopic resection was possible in 90% of the patients. Total conversion rate was 10%, but conversion due to failure of the marking of the nodule was observed in only 5% of the patients. Histology revealed 28 (37%) primary lung cancers, 24 (32%) metastases and 21 (28%) benign lesions. In 13 (23%) patients, minor complications were observed. None of them required additional interventions. CONCLUSION: The radio-guided detection of small pulmonary nodules is very accurate and safe after CT-guided injection of [99mTc]Tc-Macrosalb. Performing the operation in a hybrid room has several logistic advantages and allows using lower technetium-99m activities. The technique allows minimally invasive lung sparing resection and prevents overtreatment of benign and metastatic lesions.

CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.

BACKGROUND AND AIMS: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery. METHODS: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor. RESULTS: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting. CONCLUSIONS: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

Loss of Cdx2 Expression in Primary Tumors and Lymph Node Metastases is Specific for Mismatch Repair-Deficiency in Colorectal Cancer.

BACKGROUND: Approximately 20% of all colorectal cancers are hypothesized to arise from the "serrated pathway" characterized by mutation in BRAF, high-level CpG Island Methylator Phenotype, and microsatellite instability/mismatch repair (MMR)-deficiency. MMR-deficient cancers show frequent losses of Cdx2, a homeodomain transcription factor. Here, we determine the predictive value of Cdx2 expression for MMR-deficiency and investigate changes in expression between primary cancers and matched lymph node metastases. METHODS: Immunohistochemistry for Cdx2, Mlh1, Msh2, Msh6, and Pms2 was performed on whole tissue sections from 201 patients with primary colorectal cancer and 59 cases of matched lymph node metastases. Receiver operating characteristic curve analysis and Area under the Curve (AUC) were investigated; association of Cdx2 with clinicopathological features and patient survival was carried out. RESULTS: Loss of Cdx2 expression was associated with higher tumor grade (p = 0.0002), advanced pT (p = 0.0166), and perineural invasion (p = 0.0228). Cdx2 loss was an unfavorable prognostic factor in univariate (p = 0.0145) and multivariate [p = 0.0427; HR (95% CI): 0.58 (0.34-0.98)] analysis. The accuracy (AUC) for discriminating MMR-proficient and - deficient cancers was 87% [OR (95% CI): 0.96 (0.95-0.98); p < 0.0001]. Specificity and negative predictive value for MMR-deficiency was 99.1 and 96.3%. One hundred and seventy-four patients had MMR-proficient cancers, of which 60 (34.5%) showed Cdx2 loss. Cdx2 loss in metastases was related to MMR-deficiency (p < 0.0001). There was no difference in expression between primary tumors and matched metastases. CONCLUSION: Loss of Cdx2 is a sensitive and specific predictor of MMR-deficiency, but is not limited to these tumors, suggesting that events "upstream" of the development of microsatellite instability may impact Cdx2 expression.