Comparative Analyses of the Outcomes Between Lobectomies and Trisegmentectomies/Lingulectomies in the Surgical Management of Clinical Stage I Left Upper Lobe Non-small Cell Lung Cancer.

BACKGROUND: Lobectomies are the standard surgical intervention for lung cancer; however, recently, surgeons have considered segmentectomies for smaller tumors, with their potential for favorable survival outcomes while preserving lung function. The surgical outcomes of trisegmentectomies/lingulectomies and lobectomies for clinical stage I left upper lobe (LUL) non-small cell lung cancers (NSCLCs) remain undetermined. Thus, our study aimed to assess the differences between the short-term surgical and long-term survival outcomes in patients with clinical stage I LUL NSCLC who underwent trisegmentectomies/lingulectomies and those who underwent lobectomies. METHODS: Between 2011 and 2021, we retrospectively reviewed the data of 377 patients with clinical stage I NSCLC who had undergone LUL lobectomies or trisegmentectomies/lingulectomies. Patients were categorized into two subcohorts according to tumor size, i.e. 0-2 and 2-4 cm. To ensure preoperative demographic comparability, 1:1 propensity-score matching (PSM) was performed. RESULTS: This study focused on the 2-4 cm subcohort. Post-PSM, patients who underwent trisegmentectomies/lingulectomies had quicker operations and shorter postoperative hospital and intensive care unit lengths of stay than those who underwent lobectomies. Post-PSM, no statistically significant differences in progression-free survival (PFS) or overall survival (OS) were observed between the segmentectomy and lobectomy groups in both the 0-2 and 2-4 cm subcohorts. The multivariate analysis revealed that different surgical methods were not statistically significant factors for either PFS or OS. CONCLUSIONS: Trisegmentectomies/lingulectomies are a feasible option for clinical stage I NSCLC, with better perioperative outcomes and similar survival rates when compared with LUL lobectomies.

Plasma Cytokines Pattern as a Prognostic Marker for Esophageal Squamous Cell Carcinoma via Unsupervised Clustering Analyses.

INTRODUCTION: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC). METHODS: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed. RESULTS: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines. CONCLUSIONS: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.

Advancing accuracy in breath testing for lung cancer: strategies for improving diagnostic precision in imbalanced data.

BACKGROUND: Breath testing using an electronic nose has been recognized as a promising new technique for the early detection of lung cancer. Imbalanced data are commonly observed in electronic nose studies, but methods to address them are rarely reported. OBJECTIVE: The objectives of this study were to assess the accuracy of electronic nose screening for lung cancer with imbalanced learning and to select the best mechanical learning algorithm. METHODS: We conducted a case‒control study that included patients with lung cancer and healthy controls and analyzed metabolites in exhaled breath using a carbon nanotube sensor array. The study used five machine learning algorithms to build predictive models and a synthetic minority oversampling technique to address imbalanced data. The diagnostic accuracy of lung cancer was assessed using pathology reports as the gold standard. RESULTS: We enrolled 190 subjects between 2020 and 2023. A total of 155 subjects were used in the final analysis, which included 111 lung cancer patients and 44 healthy controls. We randomly divided samples into one training set, one internal validation set, and one external validation set. In the external validation set, the summary sensitivity was 0.88 (95% CI 0.84-0.91), the summary specificity was 1.00 (95% CI 0.85-1.00), the AUC was 0.96 (95% CI 0.94-0.98), the pAUC was 0.92 (95% CI 0.89-0.96), and the DOR was 207.62 (95% CI 24.62-924.64). CONCLUSION: Electronic nose screening for lung cancer is highly accurate. The support vector machine algorithm is more suitable for analyzing chemical sensor data from electronic noses.

Effects of high flow nasal cannula following minimally invasive esophagectomy in ICU patients: A prospective pre-post study.

BACKGROUND/PURPOSE: Patients with esophageal cancer who undergo minimally invasive esophagectomy are at risk of postoperative pulmonary complications. High-flow nasal cannula oxygen therapy delivers humidified, warmed positive airway pressure but has not been applied routinely after surgery. Here, we aimed to compare high-flow nasal cannula and conventional oxygen therapy in patients with esophageal cancer during intensive care unit hospitalization 48 h postoperatively. METHODS: In this prospective pre- and post-intervention study, patients with esophageal cancer who underwent elective minimally invasive esophagectomy (MIE) and were extubated in the operation room and admitted to the intensive care unit postoperatively were assigned to receive either high-flow nasal cannula (HFNCO) or standard oxygen (SO) therapy. Participants in the SO group were recruited before January 2020, and those in the HFNCO group were enrolled after January 2020. The primary outcome was the difference in postoperative pulmonary complication incidence. Secondary outcomes were the occurrence of desaturation within 48 h, PaO2/FiO2 within 48 h, anastomotic leakage, length of intensive care unit and hospital stay, and mortality. RESULTS: The standard oxygen and high-flow nasal cannula oxygen groups comprised 33 and 36 patients, respectively. Baseline characteristics were comparable between groups. In the HFNCO group, postoperative pulmonary complication incidence was significantly reduced (22.2% vs 45.5%) and PaO2/FiO2 was significantly increased. No other between-group differences were observed. CONCLUSION: HFNCO therapy significantly reduced postoperative pulmonary complication incidence after elective MIE in patients with esophageal cancer without increasing the risk of anastomotic leakage.

Primary Tumor Resection for Stage IV Non-small-cell Lung Cancer Without Progression After First-Line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment: A Retrospective Case-Control Study.

BACKGROUND: In studies of stage IV epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC), <10% of patients underwent surgery; thus, the effect of surgery in these patients remains unclear. We investigated whether primary lung tumor resection could improve the survival of patients with stage IV EGFR-mutant NSCLC without progression after first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. METHODS: This retrospective case-control study included patients treated with first-line EGFR-TKIs without progression on follow-up imaging. Patients in the surgery group (n = 56) underwent primary tumor resection, followed by TKI maintenance therapy. Patients in the control group (n = 224; matched for age, metastatic status, and Eastern Cooperative Oncology Group performance status) received only TKI maintenance therapy. Local ablative therapy for distant metastasis was allowed in both groups. The primary endpoint was progression-free survival. The secondary endpoints were overall survival, failure patterns, and complications/adverse events. RESULTS: The median time from TKI treatment to surgery was 5.1 months. For the surgery and control groups, the median follow-up periods were 34.0 and 38.5 months, respectively, with a median (95% confidence interval) progression-free survival of 29.6 (18.9-40.3) and 13.0 (11.8-14.2) months, respectively (P < 0.001). Progression occurred in 29/56 (51.8%) and 207/224 (92.4%) patients, respectively. The median overall survival in the surgery group was not reached. The rate of surgical complications of grade ≥2 was 12.5%; complications were treated conservatively. CONCLUSIONS: Primary tumor resection is feasible for patients with EGFR-mutant nonprogressed NSCLC during first-line EGFR-TKI treatment and may improve survival better than maintenance EGFR-TKI therapy alone.

A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy.

INTRODUCTION: Fluid therapy in critically ill patients, especially timing and fluid choice, is controversial. Previous randomized trials produced conflicting results. This observational study evaluated the effect of colloid use on 90-day mortality and acute kidney injury (RIFLE F) within the Rational Fluid Therapy in Asia (RaFTA) registry in intensive care units. MATERIALS AND METHODS: RaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI). RESULTS: Twenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635). CONCLUSION: RaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition. CLINICAL SIGNIFICANCE: Early resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research. HOW TO CITE THIS ARTICLE: Jacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028-1036.

The Differences in Clinicopathologic and Prognostic Characteristics Between Surgically Resected Peripheral and Central Lung Squamous Cell Carcinoma.

BACKGROUND: Pulmonary peripheral-type squamous cell carcinoma (p-SqCC) has been increasing in incidence. However, little is known about the clinicopathologic features of p-SqCC. This study aimed to investigate the clinicopathologic characteristics and clinical outcomes of p-SqCC compared with central-type SqCC (c-SqCC) in a large cohort of surgically resected lung SqCC patients with long-term follow-up results. METHODS: The study included 268 patients with SqCC who underwent surgical resection at the authors' institute from January 1990 to September 2013. The mean follow-up period was 67.1 months. The clinicopathologic and genetic characteristics were investigated in relation to their association with progression-free survival (PFS) and overall survival (OS) based on tumor location. RESULTS: The study cohort included 120 patients with p-SqCC and 148 patients with c-SqCC. Compared with c-SqCC, p-SqCC was correlated with older age (p = 0.002), female sex (p = 0.033), better performance status (p < 0.001), smaller tumor (p = 0.004), less lymph node metastasis (p < 0.001), and an earlier pathologic stage (p < 0.001). Despite the clinicopathologic differences, tumor location was not significantly correlated with clinical outcomes. For the p-SqCC patients, the multivariate analysis showed a significant correlation of lymphovascular invasion (PFS, p < 0.001; OS, p < 0.001) and lymph node metastasis (p = 0.007; OS, p = 0.022) with poor PFS and OS, but a significant correlation of incomplete tumor resection (PFS, p = 0.009) only with poor PFS. CONCLUSIONS: The clinicopathologic features differed between the p-SqCC and c-SqCC patients. Lymphovascular invasion and lymph node metastasis were independent prognostic factors of p-SqCC. These prognostic factors may be potentially used as indicators for adjuvant therapies to be used with patients who have p-SqCC.

Outcome of untreated lung nodules with histological but no microbiological evidence of tuberculosis.

BACKGROUND: The outcome of lung nodule(s) with histopathological findings suggestive of tuberculosis (TB) but lack of microbiologic confirmation remains unclear. Whether these patients require anti-TB treatment remains unknown. The aim of the study was to compare the risk of active TB within 4 years in untreated patients with histological findings but no microbiological evidences suggestive of TB. METHODS: From January 2008 to June 2013, patients with either solitary or multiple lung nodules having histological findings but no microbiological evidences suggestive of TB were identified from a medical center in Taiwan and were followed for 4 years unless they died or developed active TB. RESULTS: A total of 107 patients were identified. Among them, 54 (51%) were clinical asymptomatic. Biopsy histology showed granulomatous inflammation in 106 (99%), and caseous necrosis was present in 55 (51%) cases. Forty (37%) patients received anti-TB treatment, and 21 (53%) of them had adverse events, including 13 initially asymptomatic patients. Anti-TB treatment was favored in patients with caseous necrosis, whereas observation was preferred in subjects whose nodules were surgically removed. Only 1 case in the untreated group developed culture-confirmed active pulmonary TB during 4-year follow-up (1 case per 251.2 patient-years). None of the 16 cases having co-existing histologic finding of malignancy became incident TB case within a follow-up of 56.7 patient-years. CONCLUSIONS: In patients having lung nodules with only histologic features suggestive of TB, the incidence rate of developing active TB was low. Risk of adverse events and benefit from immediate treatment should be carefully considered.

Twenty-years of lung transplantation in Taiwan: Effects of cumulative institutional experience on early outcomes.

BACKGROUND/PURPOSE: Lung transplantation in Taiwan began in 1991, but the experience was limited and diverse in the early years. We examined the cumulative institutional experience of the largest lung transplant cohort in Taiwan. METHODS: A retrospective review of lung transplantations performed at a single institution from December 1995 through August 2016 was conducted. For comparative purposes, the cohort was divided into halves, with an early group (undergoing lung transplantation in the first decade) vs a late group (undergoing lung transplantation in the second decade). Standardized donor selection, organ procurement, and preservation protocols for brain-dead donors were applied. The outcomes measured were 30-day mortality and actuarial survival using the Kaplan-Meier method. RESULTS: The cohort included 50 recipients in the early group and 42 recipients in the late group. Compared with the early group, recipients in the late group were significantly older (38.8 ± 11.6 vs 44.8 ± 13.4 years, p = 0.024) and more of them required mechanical ventilation before transplant (26.0% vs 66.7%, p < 0.001). There were more female donors (12.0% vs 33.3%, p = 0.021) and gender-matched donors (34.0% vs 61.9%, p = 0.012) in the late group. A total of 87 recipients (94.6%) had cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) support during transplant, and CPB was used significantly less in the late group. Graft procedures (14.0% vs 47.6%, p < 0.001), delayed chest closure (0% vs 21.4%, p < 0.001), and early tracheostomy (24.0% vs 52.4%, p = 0.005) were performed more in the late group. The durations of hospital and ICU stays were comparable in both groups, but the 30-day mortality was significantly lower in the late group (30.0% vs 2.4%, p = 0.001). CONCLUSION: Although the results were undesirable in the first decade of the transplant program, the cumulative institutional experience led to significantly improved outcomes in the second decade of the transplant program.

Peroxiredoxin 1 induces inflammatory cytokine response and predicts outcome of cardiogenic shock patients necessitating extracorporeal membrane oxygenation: an observational cohort study and translational approach.

BACKGROUND: Extracellular peroxiredoxin 1 (Prdx1) has been implicated to play a pivotal role in regulating inflammation; however, its function in tissue hypoxia-induced inflammation, such as severe cardiogenic shock patients, has not yet been defined. Thus, the objective of this study was to test the hypothesis that Prdx1 possesses prognostic value and instigates systemic inflammatory response syndrome in cardiogenic shock patients undergoing extracorporeal membrane oxygenation (ECMO) support. METHODS: We documented the early time course evolution of circulatory Prdx1, hypoxic marker carbonic anhydrase IX, inflammatory cytokines including IL-6, IL-8, IL-10, MCP-1, TNF-α, IL-1ß, and danger signaling receptors (TLR4 and CD14) in a cohort of cardiogenic shock patients within 1 day after ECMO support. In vitro investigations employing cultured murine macrophage cell lines and human monocytes were applied to clarify the relationship between Prdx1 and inflammatory response. RESULTS: Prdx1 not only peaked earlier than all the other cytokines we studied during the initial course, but also predicted a worse outcome in patients who had higher initial Prdx1 plasma levels. The Prdx1 levels in patients positively correlated with hypoxic markers carbonic anhydrase IX and lactate, and inflammatory cytokines. In vitro study demonstrated that hypoxia/reoxygenation induced Prdx1 release from human monocytes and enhanced the responsiveness of the monocytes in Prdx1-induced cytokine secretions. Furthermore, functional inhibition by Prdx1 antibody implicated a crucial role of Prdx1 in hypoxia/reoxygenation-induced IL-6 secretion. CONCLUSIONS: Prdx1 release during the early phase of ECMO support in cardiogenic shock patients is associated with the development of systemic inflammatory response syndrome and poor clinical outcomes. Thus, circulating Prdx1 provides not only prognostic information but may be a promising target against ischemia/reperfusion injury.

The Prognostic Significance of pSTAT1 and CD163 Expressions in Surgically Resected Stage 1 Pulmonary Squamous Cell Carcinomas.

BACKGROUND: Tumor-associated macrophages (TAMs) play an important role in the initiation, progression, and metastasis of various solid tumors, and can polarize into M1 and M2 phenotypes. This study aimed to investigate whether TAM polarization is associated with clinical outcomes for early-stage pulmonary squamous cell carcinoma (SqCC). METHODS: This retrospective study included 97 consecutive patients with stage 1 pulmonary SqCC. Immunohistochemical stains for M1 macrophage marker (pSTAT1) and M2 macrophage marker (CD163) were performed on paraffin-embedded tumors. The correlations of M1 and M2 macrophage expression, clinicopathologic characteristics, and clinical outcomes were analyzed. RESULTS: The 5-year disease-free survival (DFS) rate was 63.2 %, and the 5-year overall survival (OS) rate was 74.8 %. Positive pSTAT1 expression was noted in 42 patients (43.3 %) and CD163 expression in 26 patients (26.8 %). A statistically significant negative correlation between pSTAT1 and CD163 expression was found (p = 0.015). Univariate analysis showed that extensive surgical resection, incomplete tumor excision, negative pSTAT1 expression, and positive CD163 expression were significantly correlated with both a poor DFS and a poor OS, whereas male gender was significantly correlated with a poor DFS only. Multivariate analysis showed that the pSTAT1/CD163 expression status was the only independent predictor for both DFS (p = 0.023) and OS and (p = 0.004). CONCLUSIONS: Markers identifying M1 and M2 macrophages, including pSTAT1 and CD163, can be used as prognostic indicators for patients with stage 1 pulmonary SqCC.

Long-term outcome after bilateral lung transplantation - a retrospective study from a low-volume center experience.

BACKGROUND: The aim of this study is to review the long-term outcomes of bilateral lung transplantation (BLTx) in our institution and examine the potential issues that may influence outcomes in a low-volume center. METHODS: A retrospective review of BLTx performed in our institution between July 2006 and December 2012 was conducted. Standardized donor selection, procurement, and preservation protocols for brain-dead donors were applied. Measured outcomes were in-hospital mortality and actuarial survival using the Kaplan-Meier method. RESULTS: Twenty-five consecutive patients (13 male, 12 female) underwent BLTx with a mean age of 41.8 ± 13.5 years. Before LTx, the mean body mass index was 18.3 ± 3.1 kg/m2. Seven of these patients (28%) required oxygen supplementation at rest before LTx, while the remaining patients (72%) required noninvasive mechanical ventilation (n = 6, 24%), invasive mechanical ventilation (n = 9, 36%) or extracorporeal membrane oxygenation (ECMO) (n = 3, 12%). The lung grafts were procured from brain-dead donors with the mean age of 26.8 ± 11.4 year and the best PaO2 / FiO2 ratio of 513 ± 77 before procurement. All cross match results between same-race donors and recipients were negative. The percentage of same-sex matching and CMV mismatching were 64% and 4%, respectively. The mean time listed on the transplant list was 308 ± 261 days. The mean ischemic time for the first and second grafts were 222 ± 62 and 361 ± 67 minutes. During transplantation, 22 (88%) patients depended on ECMO and one (4%) on cardiopulmonary bypass support. All but two patients (82%) were discharged home in good condition; two (8%) patients died within 3 months after BLTx. The cumulative survival rates at 1-, 2-, 3-, and 5-years were 88%, 83%, 72%, and 72%, respectively. CONCLUSIONS: Although the comparatively few annual LTx performed is consistent with the low donation rate, our single-center growing experience demonstrates that good post-lung transplant outcomes can be achieved at a low-volume LTx center.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension--A single-center experience in Taiwan.

BACKGROUND/PURPOSE: Pulmonary endarterectomy (PEA) is a potentially curative surgical procedure for patients with chronic thromboembolic pulmonary hypertension. The aim of this study is to review our institutional experience with this operation. METHODS: We conducted a retrospective review of PEA performed at our institution between January 2005 and December 2013. The measured outcomes were inhospital complications, improvement in cardiac function and exercise capacity, and actuarial survival after PEA. RESULTS: Ten consecutive patients (7 women, 3 men) underwent PEA with a mean age of 59.9 ± 12.9 years. The preoperative New York Heart Association functional class (NYHA FC) for these patients was either Class III (n = 6) or Class IV (n = 4). The period from symptom onset to diagnosis was 34.3 ± 37.9 months, and that from diagnosis to operation was 31.4 ± 46.8 months. After PEA, the duration of intensive care unit stay and hospital stay prior to discharge were 9.7 ± 5.7 days and 18.7 ± 7.4 days, respectively. Postoperative complications included reperfusion lung edema (n = 3) and pneumonia (n = 1), and all recovered with medical therapy. After a mean follow-up of 48.4 ± 35.1 months, all patients showed marked improvements in their clinical status and were still alive without evidence of disease recurrence. CONCLUSION: With proper patient selection, the cooperation of a multidisciplinary team, and meticulous postoperative management, PEA can be conducted safely with relatively low risk at a center with limited experience with the procedure.

Virological, serological, and antiviral studies in an imported human case of avian influenza A(H7N9) virus in Taiwan.

We describe the clinical course and virological characteristics of the first H7N9 influenza case in a Taiwanese patient; this patient had detectable viruses in the airway for 2 weeks, during which time an oseltamivir resistance-associated R292K mutation rapidly emerged. Anti-H7N9 antibody was detected 21 days after onset of symptoms, when H7N9 viral load declined significantly.

New aspects of the clinicopathology and genetic profile of metachronous multiple lung cancers.

OBJECTIVE: For treatment decisions and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in metachronous multiple lung cancers to differentiate multiple primary lung cancers (MPLCs) from pulmonary metastases. BACKGROUND: The current criteria to differentiate MPLCs from metastases are based on the histologic type and onset interval and do not incorporate genetic analysis. The genetic background of MPLCs remains unclear. METHODS: Ninety-seven metachronous multiple lung cancers were identified to investigate somatic mutations in p53 and EGFR. Mutational analysis of p53 and EGFR was performed on DNA extracted from paraffin-embedded tumors. RESULTS: A high frequency of somatic mutations in p53 (44.3%; 43/97) and/or EGFR (51.5%; 50/97) resulted in a high discrimination rate of tumor clonality (77.3%; 75/97) in metachronous multiple lung cancers. Of the 97 cases, 25 cases (33.3%) and 50 cases (66.7%) were assessed as having the same clonality (SC) and different clonality (DC), respectively. Notably, DC was commonly observed among tumors of the same histologic type (60.7%; 37/61), which further supported the carcinogenic theory of field cancerization. Multivariate analysis revealed that a first primary tumor of 3 cm or smaller (5-year survival: 92.7%; P = 0.001) and a limited resection of the latest tumor (5-year survival: 96.0%; P = 0.016) were 2 independent predictors of favorable prognosis. CONCLUSIONS: Because most metachronous tumors of the same histologic type have different clonal origins, clonality assessment is essential to differentiate MPLCs from metastases. We recommend limited resection as the treatment of choice to achieve long-term survival in MPLCs patients with tumors of 3 cm or smaller.

Clinicopathology and genetic profile of synchronous multiple small adenocarcinomas: implication for surgical treatment of an uncommon lung malignancy.

PURPOSE: Synchronous multiple small adenocarcinomas are detected more frequently than in the past; however, the genetic profile, treatment, and prognosis of patients remain unclear. For treatment decisions and prognostic applications, we evaluated epidermal growth factor receptor (EGFR), p53, and KRAS somatic mutations in synchronous multiple small lung adenocarcinomas. METHODS: The presence of EGFR, p53, and KRAS somatic mutations was determined in 64 synchronous multiple lung adenocarcinomas ≤2 cm in maximal dimension. Mutational analysis was performed on DNA extracted from paraffin-embedded tumors. RESULTS: Five-year disease-free survival (DFS) was 86.1 %, and overall survival was 95.8 %. EGFR, p53, and KRAS mutations were detected in 41 (64.1 %), 8 (12.5 %), and 4 (6.3 %) patients, respectively. The high frequency of genetic mutations resulted in a high discrimination rate of tumor clonality (68.8 %; 44/64) in the study group. Fourteen (31.8 %) patients were assessed as having the same clonality, whereas 30 (68.2 %) patients had different clonality, which further supported the concept of field cancerization. Multivariate analysis showed lymph node metastasis (p = 0.003) and smoking (p = 0.011) were significantly correlated with tumor relapse. Surgical method, clonality, and tumor location were not correlated with tumor relapse. CONCLUSIONS: Whether these tumors are different or the same clonal, sublobar resection of each lesion can achieve long-term DFS and is the treatment of choice for synchronous multiple small lung adenocarcinomas. Patients with lymph node metastasis are at risk of relapse and adjuvant chemotherapy is indicated.