Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.

Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy.

Cyclic GMP-AMP synthase (cGAS) binds pathogenic and other cytoplasmic double-stranded DNA (dsDNA) to catalyze the synthesis of cyclic GMP-AMP (cGAMP), which serves as the secondary messenger to activate the STING pathway and innate immune responses. Emerging evidence suggests that activation of the cGAS pathway is crucial for anti-tumor immunity; however, no effective intervention method targeting cGAS is currently available. Here we report that cGAS is palmitoylated by ZDHHC9 at cysteines 404/405, which promotes the dimerization and activation of cGAS. We further identified that lysophospholipase-like 1 (LYPLAL1) depalmitoylates cGAS to compromise its normal function. As such, inhibition of LYPLAL1 significantly enhances cGAS-mediated innate immune response, elevates PD-L1 expression, and enhances anti-tumor response to PD-1 blockade. Our results therefore reveal that targeting LYPLAL1-mediated cGAS depalmitoylation contributes to cGAS activation, providing a potential strategy to augment the efficacy of anti-tumor immunotherapy.

AhR diminishes the efficacy of chemotherapy via suppressing STING dependent type-I interferon in bladder cancer.

The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway. Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC).

Association of early immune-related adverse events with treatment efficacy of neoadjuvant Toripalimab in resectable advanced non-small cell lung cancer.

Background: Neoadjuvant immunotherapy with anti-PD-1 was proved promising in resectable non-small cell lung cancer (NSCLC). Immune-related adverse events (irAEs) have been preliminarily implicated their association with treatment efficacy. Here we elucidated the early onset of irAEs associated with better clinical outcomes in a prospective study (Renaissance study). Methods: We conducted the prospective study of NSCLC patients treated by neoadjuvant Toripalimab (240mg, every 3 weeks) plus double platinum-based chemotherapy from December 2020 to March 2022 at Peking University Cancer Hospital. Patients were enrolled if they have resectable IIB-IIIB NSCLC without EGFR/ALK mutation. Data were analyzed to explore the relationship between clinical outcome and irAEs after neoadjuvant treatment. A multidisciplinary team including physicians, surgeons, and radiologists, confirmed the irAEs according to the clinical manifestation. The relationship between irAEs and pathological outcomes was analyzed. The Renaissance study was approved by the Peking University Ethic board (2020YJZ58) and registered at https://clinicaltrials.gov/ as NCT04606303. Results: Fifty-five consecutive patients were enrolled with a male-to-female ratio of 10:1, the median age was 62 years old (IQR: 45-76), of which 44 patients (80%) were diagnosed with squamous cell carcinoma. Forty-eight of 55 patients finally received thoracic surgery with a median preoperative waiting time of 67 days (IQR 39-113 days). Pathological results demonstrated that 31 (64.6%) patients achieved major pathological response (MPR) and 24 (50.0%) achieved complete pathological response (pCR). Among 48 patients who received R0 resection, immunotherapy-related thyroid dysfunction, rash/pruritus and enteritis occurred in 11 patients (22.9%), 7 patients (14.6%), and 1 patient (2.1%), respectively. Six patients (54.5%) with thyroid dysfunction achieved MPR with 5 (45.5%) achieved pCR, and a median time to onset was 45 days (IQR 21-91 days). Six patients (85.7%) with rash or pruritus achieved MPR and 5 patients (71.4%) achieved pCR, with median time to onset being 8 days (IQR 6-29 days). Furthermore, irAEs had no significant influence on operation time (170.6 min vs 165.7 min, P=0.775), intraoperative blood loss (67.4 mL vs 64.3 mL, P=0.831) and preoperative waiting time (93 days vs 97 days, P=0.630) when comparing with patients without irAEs (Figure 1).Figure 1Comparison of operation time (A), intraoperative blood loss (B), and preoperative waiting time (C) between "with irAEs" and "without irAEs". Conclusion: The immunotherapy-related rash is potentially associated with pathological outcomes in NSCLC patients after neoadjuvant chemo-immunotherapy, suggesting easy-to-find irAEs, such as rash, can be used as indicators to predict response to neoadjuvant chemo-immunotherapy.Clinical trial registration: clinicaltrials.gov/, identifier NCT04606303.

Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins.

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.

Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial.

OBJECTIVES: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC. MATERIALS AND METHODS: This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. RESULTS: Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1 % (27/38) (95 % confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8 %) underwent successful R0 resection. Thirty (75.0 %) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5 %) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n = 20 [50 %]), diarrhea (n = 12 [30 %]), and oral ulceration (n = 12 [30 %]). CONCLUSIONS: The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC.

ß-Ionone represses renal cell carcinoma progression through activating LKB1/AMPK-triggered autophagy.

ß-Ionone, the end ring analog of ß-carotenoids, has been proven to have an antitumor effect in a variety of cancers. In this study, we investigated the impact of ß-ionone on renal cell carcinoma (RCC) cell lines (786-O and ACHN) using colony formation assays, flow cytometry analysis, and western blot analysis. We found that ß-ionone effectively inhibited the proliferation of RCC cells in vitro, which was also confirmed in a xenograft model. Moreover, we found that ß-ionone could induce autophagy, as indicated by LC3 puncta in 786-O and ACHN cell lines and the expression of LC3 in ß-ionone-treated RCC cells. To further explore the underlying mechanism, we assessed liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway activity, and the results showed that ß-ionone inhibited the proliferation of RCC cells by inducing autophagy via the LKB1/AMPK signaling pathway. In summary, our findings provide a new therapeutic strategy of ß-ionone-induced autophagy in RCC.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Intermittent chest tube clamping decreases chest tube duration time and drainage volume after lung cancer surgery in patients without air leak: an open-label, randomized controlled trial.

Background: Our previous retrospective study proved the safety and effectiveness of chest tube clamping in terms of shortening chest tube duration. However, it needed to be verified by a prospective study. This study sought to determine if intermittent chest tube clamping decreases chest tube duration and total drainage volume after lung cancer surgery in patients without air leak. Methods: Patients with resectable lung cancer scheduled to undergo lobectomy were identified as potential candidates. Once the re-expansion of the lung was confirmed via radiography the morning of postoperative day 1 and no air leak was detected, 180 patients were randomly assigned to intermittent chest tube clamping (the clamping group, n=90) or continuous gravity drainage (the control group, n=90). The primary outcome was chest tube drainage duration. Pleural drainage volume and adverse events were also recorded. Results: Of 180 patients, 12 were subsequently withdrawn from the study for various reasons. In the intention-to-treat analysis, the chest tube drainage duration was significantly shorter {median [interquartile range]: 2 [2, 3] vs. 3 [2, 3] days; P=0.009}, and total drainage volume was much less (mean ± standard deviation: 516.73±410.9 vs. 657.8±448.2 mL; P=0.029) in the clamping group than the control group. In the per-protocol analysis, the chest tube drainage duration was significantly shorter {median [interquartile range]: 2 [2, 3] vs. 3 [2, 3] days; P=0.007}, and total drainage volume was much less (mean ± standard deviation: 437.8±213.9 vs. 604.8±352.8 mL; P=0.001) in the clamping group than the control group. Further, the clamping group showed a major improvement in plasma albumin declination at discharge (mean ± standard deviation: 7.7±2.9 vs. 9.0±5.2 g/L; P=0.040). No severe adverse events were observed in either 2 groups. Conclusions: Our study indicates that chest tube clamping decreased the duration of chest tube drainage and drainage volume without causing adverse effects. Its wider application may help reduce medical costs and increase patient comfort. Trial Registration: ClinicalTrials.gov NCT03379350.

Inflammatory factor-based prognostic risk stratification for patients with metastatic castration-resistant prostate cancer treated with docetaxel.

To develop a simple inflammatory factor-based prognostic risk stratification system for patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel as the initial treatment, we reviewed the data of 399 consecutive patients who received first-line docetaxel chemotherapy between January 2013 and June 2019 retrospectively. The optimal cut-off values for the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in terms of survival were calculated by ROC curves. Patients were stratified into favourable (lower NLR and lower PLR), intermediate (higher NLR and lower PLR, or lower NLR and higher PLR) and poor (higher NLR and higher PLR) groups. Kaplan-Meier curves were drawn to evaluate overall survival (OS) and progression-free survival (PFS). The ROC curve analysis determined the cut-offs for the NLR and PLR to be 2.355 and 104.275 respectively. Multivariate Cox regression analysis showed that being in the poor patient group (NLR ≥2.355 and PLR ≥104.275) was an independent prognostic risk factor and Kaplan-Meier curves analysis revealed that respondents with NLR <2.355 and PLR <104.275 had significantly longer OS and PFS. So it can be concluded that concurrently high NLR and PLR values are predictors for poor chemotherapy outcomes after androgen deprivation therapy failure in patients with mCRPC.

Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer.

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) N classifications, which depend on the location and involvement of the lymph nodes, provide accurate prognoses. This study validated the efficiency of classifications using a single-institution dataset and proposed a modified system based on 5-level N1 node dissection. METHODS: From January 2005 to December 2014, 1851 patients with completely resected non-small cell lung cancer were reviewed. According to the IASLC recommendations, N1 is further subdivided into N1a (single) and N1b (multiple), N2 is divided into N2a1 (single station without N1), N2a2 (single station with N1), and N2b (multiple station). Additionally, we evaluated dividing N0 into N0a (with level 13/14 examination) and N0b (without level 13/14 examination), and N1 into N1a* (only level 13/14 positive) and N1b* (level 10-12 positive). Overall survival was also compared. RESULTS: Multivariate analysis showed that the N classifications recommended by the IASLC and those proposed and evaluated by this study could both significantly predict the prognoses of patients (p < 0.001, respectively). There was no significant difference in survival between N1b and N1a (hazard ratio [HR] 1.049, p = 0.83) and N2a1 and N1b (HR 1.314, p = 0.261); however, there were significant differences between N0a and N0b (HR 1.778, p < 0.001) and N1a* and N1b* (HR 2.014, p = 0.019). The survival curve of N1a* overlapped N0b (HR 0.997, p = 0.991), and N2a1 overlapped N1b* (HR 0.842, p = 0.444). CONCLUSION: More detailed nodal information is required to facilitate future revisions of N staging.

Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study.

Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.

Impact of Early Oral Feeding on Anastomotic Leakage Rate After Esophagectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Esophageal cancer occupies a vital position in fatal cancer-related disease, with esophagectomy procedures helping to improve patient survival. The timing when oral intake should be resumed after esophagectomy and whether early oral feeding (EOF) or delayed oral feeding (DOF) should be the optimal regimen are controversial. METHODS: Databases (PubMed, Embase, Cochrane library) were searched. All records were screened by two authors through full-text reading. Data on the anastomotic leakage rate were extracted and synthesized in meta-analyses. Postoperative pneumonia rate and length of hospital stay were also assessed. RESULTS: Seven studies from 49 records were included after full-text reading; 1595 patients were totally included in the analysis. No significant difference was observed between the EOF and DOF groups (odds ratio [OR] 1.68; 95% confidence interval [CI] 0.70-4.03; p = 0.2495; I2 = 70%). Higher anastomotic leakage rate was observed in EOF compared with DOF (OR 2.89; 95% CI 1.56-5.34; p = 0.0007; I2 = 10%) in the open subgroup. No significant difference was observed in the MIE (OR 0.48; 95% CI 0.22-1.02; p = 0.0564; I2 = 0%). Patients performed similarly in pneumonia (OR 1.12; 95% CI 0.57-2.21; p = 0.745; I2 = 34%). In cervical subgroup, anastomosis leakage may be less in DOF (OR 2.42 95% CI 1.26-4.64; p = 0.0651; I2 = 58%), while in thoracic subgroup, there is no obvious difference (OR 0.86 95% CI 0.46-1.61; p = 0.01; I2 = 84.9%). CONCLUSIONS: Anastomotic leakage related to the timing of oral feeding after open esophagectomy, which is more favorable to the DOF regimen. However, timing of oral feeding did not impair anastomotic healing in patients undergoing MIE.

Metachronous or synchronous primary lung cancer in the era of computed tomography surveillance.

OBJECTIVES: The purpose of this study was to determine the frequency, characteristics, and survival of second primary lung cancer initially identified as an indeterminate lesion on the original computed tomography scan and then diagnosed during the surveillance period in a prospective study. METHODS: A prospective database of 271 patients enrolled in a surveillance study was updated. Indeterminate lesions present on the original computed tomography at the time of initial primary lung cancer diagnosis that subsequently grew and were diagnosed as cancer were termed "synchronous primary lung cancer." Lesions that were not present on the original computed tomography scan and subsequently diagnosed on surveillance were termed "metachronous primary lung cancer." RESULTS: Thirty patients (11.1%) developed 37 second primary lung cancers over a median surveillance period of 84.7 (range, 15.9-147.6) months. Of these, 15 of 37 (40.5%) were identified as synchronous primary lung cancer, and 22 of 37 (59.5%) were identified as metachronous primary lung cancer. At first identification, ground-glass lesions were identified in 9 of 15 (60%) synchronous primary lung cancers compared with only 5 of 22 (22.7%) of metachronous primary lung cancers (P = .034). Compared with metachronous primary lung cancer, from first identification to diagnosis, synchronous primary lung cancer developed over a longer interval (33.6 vs 7.2 months, P = .001) and had a slower growth rate (0.17 vs 0.45 mm/month, P = .027). The 5-year overall survival from second lung cancer was 73.0%. No significant differences were observed between the synchronous primary lung cancer and metachronous primary lung cancer cohorts in overall survival from initial primary lung cancer (P = .583) or from second lung cancer (P = .966). CONCLUSIONS: Computed tomography surveillance identifies 2 types of curable second lung cancers leading to excellent overall survival.

TriZ-a rotation-tolerant image feature and its application in endoscope-based disease diagnosis.

Endoscopy is becoming one of the widely-used technologies to screen the gastric diseases, and it heavily relies on the experiences of the clinical endoscopists. The location, shape, and size are the typical patterns for the endoscopists to make the diagnosis decisions. The contrasting texture patterns also suggest the potential lesions. This study designed a novel rotation-tolerant image feature, TriZ, and demonstrated the effectiveness on both the rotation invariance and the lesion detection of three gastric lesion types, i.e., gastric polyp, gastric ulcer, and gastritis. TriZ achieved 87.0% in the four-class classification problem of the three gastric lesion types and the healthy controls, averaged over the twenty random runs of 10-fold cross-validations. Due to that biomedical imaging technologies may capture the lesion sites from different angles, the symmetric image feature extraction algorithm TriZ may facilitate the biomedical image based disease diagnosis modeling. Compared with the 378,434 features of the HOG algorithm, TriZ achieved a better accuracy using only 126 image features.

Detection of circulating tumor cells in pulmonary venous blood for resectable non-small cell lung cancer.

Intraoperative manipulation causes circulating tumor cell (CTC) shedding into the blood and accelerates metastasis in non-small cell lung cancer (NSCLC). The present study was conducted to assess the degree of dissemination resulting from surgery and to explore the biological features of CTCs. In patients with NSCLC who underwent complete resection, the pulmonary vein (PV) was isolated and stapled following thoracotomy. The number of CTCs retained per 7.5 ml PV blood (CTC-PV) and peripheral blood were detected. Following hematopoietic cell depletion, a xenograft assay was performed using the CTC-PV. A total of 32 consecutive patients were enrolled in the study, the majority of whom had CTCs in their PV blood (n=29, 90.6%). Circulating tumor microemboli (CTM) were identified in 12 patients (37.5%). The CTC-PV and CTM-PV counts were positively correlated with tumor size (P=0.012 and P=0.028, respectively). Patients with small tumors (<3.0 cm) also had considerable CTC-PV and CTM-PV. A total of 8 patients received platinum-based chemotherapy prior to surgery. The CTC-PV and CTM-PV counts in patients with partial response were significantly lower than those in patients with stable disease or who did not receive induction therapy (P=0.025 and P=0.044, respectively). The enriched CTC-PV from 3 patients were injected into 3 immunodeficient mice, and 1 mouse developed a xenograft tumor. To conclude, the present study indicates that intraoperative manipulation contributes to the hematogenous dissemination of tumorigenic CTCs and CTM. Lobectomy is recommended for lung cancer of any tumor size and stage according to oncological principles, in addition to ligating the PV, if possible, prior to any other treatment.

Adjuvant chemotherapy may improve outcome of patients with non-small-cell lung cancer with metastasis of intrapulmonary lymph nodes after systematic dissection of N1 nodes.

OBJECTIVE: Survival benefit of adjuvant chemotherapy (AC) of patients with intrapulmonary lymph node (IPLN) metastasis (level 12-14) needs investigation. We evaluated the impact of AC on patients whose metastatic nodes were limited to intrapulmonary levels after systematic dissection of N1 nodes. METHODS: First, 155 consective cases of lung cancer confirmed as pathologic N1 were collected and evaluated. Patients received systematic dissection of N2 and N1 nodes. For patients with IPLN metastasis, survival outcomes were compared between those receiving AC and those not receiving AC. RESULTS: In this group, 112 cases (72.3%) had IPLN metastasis and 55 cases (35.5%) had N1 involvement limited to level 13-14 without further disease spread to higher levels. Patients with IPLN involvement had a better prognosis than that of patients with hilar-interlobar involvement. For the intrapulmonary N1 group (level 12-14-positive, level 10-11-negative or unknown, n=112), no survival benefit was found between the AC group and non-AC group [5-year overall survival (OS): 54.6±1.6vs. 50.4±2.4 months, P=0.177]. However, 76 of 112 cases for whom harvesting of level-10 and level-11 nodes was done did not show cancer involvement in pathology reports (level 12-14-positive, level 10-11 both negative), oncologic outcome was better for patients receiving AC than those not receiving AC in this subgroup (5-year OS: 57.3±1.5vs. 47.1±3.2 months, P=0.002). CONCLUSIONS: Oncologic outcome may be improved by AC for patients with involvement of N1 nodes limited to intrapulmonary levels after complete examination of N1 nodes.

Impact of Omission of Intrapulmonary Lymph Node Retrieval on Outcome Evaluation of Lung Cancer Patients Without Lymph Node Metastasis: A Propensity Score Matching Analysis.

INTRODUCTION: Clinical practice of retrieval of segmental (station 13) and subsegmental (station 14) lymph nodes for pathologic examination varies during lung cancer surgery. This study aimed to evaluate whether omitting retrieval of nodes from stations 13 and 14 could affect outcome evaluation for patients with pN0 non-small-cell lung cancer (NSCLC). METHODS: This retrospective study analyzed 442 patients with NSCLC who were treated with both R0 resection and systematic mediastinal lymphadenectomy with pathologically confirmed stage pN0 NSCLC. The study group included patients in whom N1 nodes including stations 10 to 14 were investigated, and the control group included patients in whom stations 10 to 12 only were investigated. Clinical and pathologic parameters of the groups were balanced by propensity score matching, and oncologic outcomes were assessed by the log-rank test. RESULTS: A total of 435 cases were included in the final analysis (170 in the study group and 265 in the control group). In the study group, a mean ± SD of 5.0 ± 3.0 nodes per case were collected from nodes 13 and 14. After propensity score matching, 143 cases were included in each group. Overall and disease-free survival improved in the study group compared to the control group (P = .027 and P = .021, respectively). T staging and intrapulmonary node collection were prognostic factors for pN0 cases. CONCLUSION: Inferior oncologic outcomes of pN0 cases without intrapulmonary node retrieval suggest that the procedure of intrapulmonary lymph node retrieval may play a role in outcome evaluation for pN0 NSCLC patients.

Intermittent chest tube clamping may shorten chest tube drainage and postoperative hospital stay after lung cancer surgery: a propensity score matching analysis.

BACKGROUND: Postoperative pleural drainage markedly influences the length of hospital stay and the financial costs of medical care. The safety of chest tube clamping before removal has been documented. This study aims to determine if intermittent chest tube clamping shortens the duration of chest tube drainage and hospital stay after lung cancer surgery. METHODS: We retrospectively analyzed 285 consecutive patients with operable lung cancer treated using lobectomy and systematic mediastinal lymphadenectomy. The chest tube management protocol in our institution was changed in January 2014, and thus, 222 patients (clamping group) were managed with intermittent chest tube clamping, while 63 patients (control group) were managed with a traditional protocol. Propensity score matching at a 1:1 ratio was applied to balance variables potentially affecting the duration of chest tube drainage. Analyses were performed to compare drainage duration and postoperative hospital stay between the two groups in the matched cohort. Multivariate logistic regression analyses were performed to predict the factors associated with chest tube drainage duration. RESULTS: The rates of thoracocentesis after chest tube removal were similar between the clamping and control groups in the whole cohort (0.5% vs. 1.6%, P=0.386). The rates of pyrexia were also comparable in the two groups (2.3% vs. 3.2%, P=0.685). After propensity score matching, 61 cases remained in each group. Both chest tube drainage duration (3.9 vs. 4.8 days, P=0.001) and postoperative stay (5.7 vs. 6.4 days, P=0.025) were significantly shorter in the clamping group than in the control group. Factors significantly associated with shorter chest tube drainage duration were female sex, chest tube clamping, left lobectomy, and video-assisted thoracoscopic surgery (VATS) (P<0.05). CONCLUSIONS: Intermittent postoperative chest tube clamping may decrease the duration of chest tube drainage and postoperative hospital stay while maintaining patient safety.