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In 1995, Ginsberg et al. compared lobectomy with limited resection including segmentectomy and wide-wedge resection for stage I lung cancer in a randomized controlled trial and found that limited resection should not be applied to otherwise healthy patients with clinical stage IA lung cancer who can tolerate lobectomy. However, recent advances in diagnostic technology have improved the precision of detecting early-stage and small lung cancers. Therefore, whether radical segmentectomy, anatomical segmentectomy with hilar and mediastinal lymph node dissection (that is more valuable than wedge resection in terms of oncological aspects) and lobectomy are comparable in terms of curative intent for patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. The role of segmentectomy differs according to tumor or patient characteristics. High resolution computed tomography findings of tumor size, location, and the presence or ratio of a ground glass opacity (GGO) component and the maximum of standardized uptake value on fluorine-18-2-deoxy- d -glucose positron emission tomography are important for selecting surgical procedures because the malignant potential of even early-stage NSCLC is variable. The ongoing JCOG0802/WJOG4607L, JCOG1211, and CALGB140503 trials will disclose the influence of segmentectomy for patients with early-staged NSCLCs that are small peripheral tumors based on preoperative high-resolution computed tomography findings about preserved pulmonary function and long-term prognosis. Segmentectomy is a key surgical procedure that general thoracic surgeons will need to master considering that it can be converted to lobectomy if the surgical margin is insufficient or lymph node metastasis is intraoperatively confirmed.

BackgroundSegmentectomy has been increasingly used for lung cancer treatment, however there are very limited data evaluating the postoperative pulmonary function of patients treated with complex segmentectomy. We evaluated the postoperative pulmonary function of patients who underwent complex segmentectomy compared with simple segmentectomy, wedge resection, and lobectomy.MethodsWe retrospectively analyzed data from 580 patients who underwent surgical resection. The patients were divided into four groups: complex segmentectomy (n = 135), simple segmentectomy (n = 83), wedge resection (n = 89), and lobectomy (n = 273). Functional testing included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and predicted diffusing capacity of the lung for carbon monoxide (%DLCO) measured preoperatively and at 12 months after surgery.ResultsDuring the postoperative course, the complex segmentectomy and simple segmentectomy groups showed a comparable course of pulmonary function. The complex segmentectomy group significantly preserved pulmonary function compared with the lobectomy group (FVC, p = 0.017; FEV1, p = 0.010; %DLCO, p = 0.0043). A similar trend was observed even when restricted to lung diseases in the right upper lobe. On the other hand, when comparing complex segmentectomy with wedge resection, complex segmentectomy showed a trend that was more disadvantageous than wedge resection, but this difference was not significant (FVC, p = 0.19; FEV1, p = 0.40; %DLCO, p = 0.96).ConclusionsComplex segmentectomy showed comparable postoperative pulmonary functions as simple segmentectomy. Complex segmentectomy could preserve pulmonary function significantly compared with lobectomy and did not result in significant loss compared with wedge resection.

BackgroundThis study aimed to investigate the efficacy of the Deauville criteria (a 5-point visual scale criteria) in assessing the accumulation of [18F]-fluoro-2-deoxy-d-glucose (FDG) on positron-emission tomography (PET)/computed tomography (CT) for predicting prognosis of early-stage lung adenocarcinoma and selecting candidates for sublobar resection.MethodsThis retrospective study included 648 patients undergoing curative resection for clinical N0 lung adenocarcinoma with a whole tumor size of 3 cm or smaller between April 2007 and March 2019. Accumulations of the FDG on PET/CT scans were scored using the Deauville criteria (Deauville score), and correlations between the Deauville score and prognosis were analyzed.ResultsThe recurrence-free survival (RFS) was significantly better for the patients with a Deauville score of 1 or 2 (n = 415, 5-year RFS, 92.6%) than for those with a score of 3 (n = 82, 5-year RFS, 72.7%; P < 0.001) or a score of 4 or 5 (n = 151, RFS, 70.8%; P < 0.001). The RFS did not differ significantly among the patients with Deauville scores of 1 and 2 who underwent wedge resection (n = 102, 5-year RFS, 90.5%), segmentectomy (n = 188, RFS, 95.1%; P = 0.355), and lobectomy (n = 125, RFS, 91.1%; P = 0.462).ConclusionThe 5-point-scale evaluation of FDG accumulation on PET/CT was useful in predicting the prognosis for patients with early-stage lung adenocarcinoma. Lung adenocarcinoma patients with a whole tumor size of 3 cm or smaller and a Deauville score of 1 or 2 can be candidates for sublobar resection.

BackgroundThe optimal extent of lymph node dissection (LND) for hypermetabolic tumors that are associated with high rates of nodal disease, recurrence, or mortality has not been elucidated.MethodsWe reviewed 375 patients who underwent lobectomy with lymphadenectomy for clinical T2–3 N0–1 M0 hypermetabolic non-small cell lung cancer (NSCLC) [maximum standard uptake value (SUVmax) ≥ 6.60] via a multicenter database. Extent of LND was classified into systematic mediastinal LND (systematic LND) and lobe-specific mediastinal LND (lobe-specific LND). Postoperative outcomes after lobectomy with systematic LND (n = 128) and lobe-specific LND (n = 247) were analyzed for all patients and their propensity-score-matched pairs.ResultsCancer-specific survival (CSS) and recurrence-free interval (RFI) of the systematic LND group were not significantly different from those of the lobe-specific LND group in the nonadjusted whole cohort. In the propensity-score-matched cohort (101 pairs), systematic LND dissected significantly more lymph nodes (20.0 versus 16.0 nodes, P = 0.0057) and detected lymph node metastasis more frequently (53.5% vs. 33.7%, P = 0.0069). Six (5.9%) patients in the systematic LND group had a metastatic N2 lymph node “in the systematic LND field” that lobe-specific LND could not dissect. The systematic LND group tended to have better prognosis than the lobe-specific LND group (5-year CSS rates, 82.6% versus 69.6%; 5-year RFI rates, 56.6% vs. 47.3%).ConclusionsSystematic LND was found to harvest more metastatic lymph nodes and provide better oncological outcome than lobe-specific LND in a cohort of hypermetabolic NSCLC patients.

SummaryPurpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.

Purpose This study aimed to elucidate the feasibility of repeated ipsilateral anatomical pulmonary resection. Methods The subjects of this retrospective analysis were 50 patients who underwent ipsilateral anatomical pulmonary resection after major lung surgery. The patients were divided into two groups according to the type of primary operation performed: a repeated anatomical pulmonary resection group (RA group; n  = 24) and an anatomical pulmonary resection after wedge resection group (AW group; n  = 26). We compared the perioperative outcomes of the two groups. Results Completion lobectomy was performed in 9 of the 24 patients (38%) from the RA group and adhesion of the pulmonary hilum was more severe in this group ( P  = 0.004). Although the operative time was significantly longer in the RA group ( P  = 0.030), there was no significant difference in the amount of blood loss ( P  = 0.217) between the groups. A significantly higher rate of severe postoperative complications was observed in the RA group (42%) than in the AW group (12%) ( P  = 0.024). None of the patients who underwent repeated surgery died within 90 days postoperatively. Conclusion Although repeated anatomical pulmonary resection is a more challenging procedure than anatomical resection after wedge resection, it does not increase short-term mortality; therefore, it is a feasible treatment option.

BackgroundAnatomic resection with lymph node dissection or sampling is the standard treatment for early non-small cell lung cancer (NSCLC), and wedge resection is an option for compromised patients. This study aimed to determine whether wedge resection can provide comparable prognoses for elderly patients with NSCLC. MethodsThe study analyzed the clinicopathologic findings and surgical outcomes during a median follow-up period of 39.6 months for 156 patients with solid dominant (consolidation-to-tumor ratio > 0.5) small (whole tumor size ≤ 2 cm) NSCLC among 892 patients 80 years of age or older with medically operable lung cancer between April 2015 and December 2016.ResultsThe 3-year overall survival (OS) rates after wedge resection and after segmentectomy plus lobectomy did not differ significantly (86.5 %; 95 % confidence interval [CI], 74.6–93.0 % vs 83.7 % 95 % CI, 74.0–90.0 %; P = 0.92). Multivariable Cox regression analysis of OS with propensity scores showed that the surgical procedure was not an independent prognostic predictor (hazard ratio [HR], 0.84; 95 % CI, 0.39–1.8; P = 0.64). The 3-year OS rates were slightly better after wedge resection for 97 patients who could tolerate lobectomy than after segmentectomy plus lobectomy (89.4 %; 95 % CI, 73.8–95.9 % vs 75.8 %; 95 % CI, 62.0–85.2 %; P = 0.14). The cumulative incidence of other causes for death was marginally higher after segmentectomy plus lobectomy than after wedge resection (P = 0.079).ConclusionsWedge resection might be equivalent to lobectomy or segmentectomy for selected patients 80 years of age or older with early-stage NSCLC who can tolerate lobectomy.

Lymphovascular invasion (LVI) is a fundamental step toward the spread of cancer. Extracellular vesicles (EVs) promote cellular communication by shuttling cargo, such as microRNAs (miRNAs). However, whether EV-associated miRNAs serve as biomarkers for LVI remains unclear. This study aimed to identify EV-associated miRNAs related to LVI and validate the miRNA levels from patients with early-stage lung adenocarcinoma (LADC). Blood samples were collected from patients undergoing pulmonary resection for stage I LADC before surgery. The patients were classified into three groups according to the presence of LVI and postoperative recurrence. Serum-derived EVs in the derivation cohort were used for small RNA sequencing, while the selected LVI miRNA candidates were validated via real-time quantitative polymerase chain reaction using 44 patient and 16 healthy donor samples as the validation cohorts. Five miRNAs (miR-99b-3p, miR-26a-5p, miR-93-5p, miR-30d-5p, and miR-365b-3p) were assessed, and miR-30d-5p ( p  = 0.036) levels were significantly downregulated in the LVI-positive group. miR-30d-5p levels in healthy donors were lower than those in LADC patients. Patients with high miR-30d-5p levels had favorable survival compared to those with low miR-30d-5p levels. miR-30d-5p level in EVs may serve as a promising biomarker for detecting LVI in patients with early-stage LADC.

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29–11.70] ng/mL vs. 3.55 [2.07–5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.