Yongbin Lin

Characteristics and Prognostic Analysis of 69 Patients With Pulmonary Sarcomatoid Carcinoma.

Background:Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy. Methods:A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis. Results:PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (≥18.5), with normal hemoglobin, with smaller tumor size (⩽4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05). Conclusions:PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.

Fish Oil-Supplemented Parenteral Nutrition in Patients Following Esophageal Cancer Surgery: Effect on Inflammation and Immune Function

Our aim was to investigate whether adding ω-3 polyunsaturated fatty acids (PUFAs) to parenteral nutrition (PN) could reduce inflammation and improve immune function in patients following esophageal cancer surgery. In this pilot study, 60 patients with esophageal cancer were divided into 2 groups (30 patients in each group). All patients had total scores of more than or equal to 3 on the nutritional risk screening (NRS2002) test recommended by the European Society of Parenteral Enteral Nutrition, which showed that all patients had nutritional risk and should receive nutritional support. Both groups received isocaloric and isonitrogenous PN. One group received a ω-3 PUFAs supplement. Key indicators of inflammation [serum procalcitonin (PCT) level and the ratio of CD4+ to CD8+ (CD4+/CD8+ ratio)] were determined intraoperatively and 24, 72, and 144 h postoperatively. PCT level was notably lower and CD4+/CD8+ ratio was markedly higher in the ω-3 PUFAs group (P = 0.007 for PCT level and P = 0.012 for CD4+/CD8+ ratio) on postoperative day 6 but not on postoperative days 1 and 3. ω-3 PUFAs supplemented PN can reduce inflammation and improve immune function in patients following esophageal cancer surgery. A larger trial is required to see whether ω-3 PUFAs supplementation of PN improves the clinical outcomes of patients following esophageal cancer surgery.

Prognostic impact of pattern-based grading system by the new IASLC/ATS/ERS classification in Asian patients with stage I lung adenocarcinoma

OBJECTIVES We examined the prognostic effect of the grading system based on the new IASLC/ATS/ERS classification in an Asian cohort of patients with early-stage lung adenocarcinoma. MATERIALS AND METHODS Patients with a lung adenocarcinoma less than 3cm in diameter that had undergone complete anatomic resection, diagnosed with pT1a-2aN0M0 consecutively from 2004 to 2013, were enrolled. All specimens were reviewed according to the new IASLC/ATS/ERS classification. The growth patterns were divided into three major categories: grade 1 for lepidic growth, grade 2 for acinar and papillary patterns, and grade 3 for solid and micropapillary patterns. Each tumor was then graded according to the modified grading system, the final score being the sum of the two most predominant grades. The correlations of clinical and pathological factors with disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS In total, 201 adenocarcinomas were eligible for score grading. Only 37 (18.4%) patients had a pure pathological growth pattern. Higher stage, greater tumor diameter, positive lymphovascular invasion, and a higher score were associated with shorter DFS. In contrast, stage no longer had a significant impact on OS in a multivariable analysis. Acinar/papillary-predominant tumors with a score of 3 or 4 were associated with better survival than those with a score of 5 (5-year DFS rate: 64.68 vs. 44.18%, HR=2.19, 95% CI: 1.24-3.87; 5-year OS rate: 85.61 vs. 68.59%, HR=3.03, 95% CI: 1.25-7.32). CONCLUSION The architectural scores may help to stratify survival differences among certain predominant growth subtypes of adenocarcinoma.

Surgical treatment for limited-stage primary small cell cancer of the esophagus.

BACKGROUND Primary small cell cancer of the esophagus (PSCCE) is a rare, aggressive, and highly metastatic disease. Surgical intervention, radiotherapy, and chemotherapy have been used alone or in combination to improve survival. This retrospective study tried to evaluate the significance of surgical procedures for the treatment of limited-stage PSCCE. METHODS We retrospectively evaluated 44 patients with limited-stage PSCCE who received esophagectomy with lymphadenectomy in our center between 1994 and 2011. The clinical and pathologic characteristics, median survival time (MST), overall survival (OS), and relevant prognostic factors were analyzed. RESULTS The MST in our cohort was 18.0 months (95% confidence interval [CI], 9.6-26.4 months), and the 6-, 12-, 24-, 36-, and 60-month OS rates were 73%, 58%, 39%, 30%, and 18%, respectively. The MST of patients with positive lymph nodes was significantly shorter than that of those with negative lymph nodes (14 months versus 47 months; p = 0.031). Survival analysis confirmed that regional lymph node involvement (relative risk [RR], 5.287; 95% CI, 1.036-26.978; p = 0.045) was an independent prognostic factor. CONCLUSIONS Although the standard treatment protocol for PSCCE has not been established, the results of our study indicated that radical esophagectomy with extended lymphadenectomy should be considered as the primary treatment for patients with limited-stage PSCCE, particularly for those without regional lymph node involvement.

Localization of peripheral pulmonary lesions to aid surgical resection: a novel approach for electromagnetic navigation bronchoscopic dye marking

OBJECTIVES Video‐assisted thoracoscopic sublobar resection of ultra‐small, non‐visible and non‐palpable pulmonary lesions is challenging. The purpose of this study was to explore an alternative and efficient method for the localization of pulmonary lesions using electromagnetic navigation bronchoscopy (ENB). METHODS Between May 2015 and April 2016, 24 consecutive patients with 30 pulmonary peripheral lesions underwent video‐assisted thoracoscopic surgery for sublobar resection in our hospital. ENB was performed before surgery to guide a catheter adjacent to the target lesion, and fibrin sealant mixed with methylene blue was injected. RESULTS All patients underwent ENB with pleural dye marking followed immediately by surgery. No surgical complications occurred. The median size of the nodules was 11.0 mm (range, 6‐19 mm). The median navigation time was 18.0 min (range, 13 to 120 min), and the average interval between dye marking and thoracic surgery was 22.1 min (range, 15‐40 min). In all cases, the target pulmonary parenchyma was stained and had tactile sense with few complications. All lesions were fully excised, and pathological examination confirmed the accuracy of the dye staining. CONCLUSIONS Fibrin sealant mixed with methylene blue injection with ENB guidance is a new effective approach to localize even ultra‐small and non‐palpable pulmonary lesions. The visible staining and tactile sensation of this method may allow more rapid intraoperative identification of lesions.

Detection of rearrangement of anaplastic lymphoma kinase (ALK) and mutation of epidermal growth factor receptor (EGFR) in primary pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a distinct rare subtype of lung cancer. The prevalence of anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutation in primary pulmonary LELC had not been thoroughly investigated. METHODS We investigated a cohort of 42 patients with primary pulmonary LELC and genotyped for ALK rearrangement and EGFR mutation. ALK rearrangement was detected by fluorescence in situ hybridization (FISH). EGFR mutational analysis of exons 18 through 21 was analyzed by TaqMan real-time polymerase chain reaction (PCR). RESULTS Epstein-Barr virus-encoded RNAs (EBERs) showed positive signals in all 42 patients. By immunohistochemistry staining, all patients demonstrated positive expression of CK5/6 and P63, but almost all patients were negative for TTF-1 (34/34, 100%) or CK7 (34/35, 97.1%). None of the 42 patients had ALK rearrangement. Of 42 patients tested, only one patient (2.4%) harbored L858R mutation and gefitinib was applied to this case, however no objective response was observed and the progression free survival (PFS) time was only 1 month. CONCLUSIONS Primary pulmonary LELC is a unique histological subtype of lung cancer. ALK rearrangement and EGFR mutation are lack and they may not be the oncogenic driver gene in pulmonary LELC. Future efforts should be made to explore other oncogenic driver gene to guide targeted therapy in this rare disease to determine the optimal treatment.

An Elevated Peripheral Blood Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma.

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. In this study, we retrospectively reviewed the data from 74 consecutive patients with pulmonary LELC and investigated the prognostic value of pretreatment monocyte-to-lymphocyte ratio (MLR). The cut-off value determined by ROC curve for MLR was 0.262. According to this cut-off value, 36 (48.6%) patients had lower MLR value (<0.262) at diagnosis. There was no significant correlation between MLR level and gender, age, smoking history, stage, and lactate dehydrogenase (LDH) level. The 2-year, 5-year, and 10-year OS rate were 86%, 72%, and 61%, respectively; the 2-year, 5-year, and 10-year PFS rate were 71%, 63%, and 49%, respectively. In univariate analysis, advanced stage, elevated LDH level, and higher MLR value (> = 0.262) were significantly associated with poor OS and PFS. In a multivariate Cox regression model that included stage, LDH and MLR level, all of these three factors were found to be independent prognostic factors for both PFS and OS. In patients who received radical surgery, MLR level remained significantly correlated with OS and PFS. In conclusion, we firstly demonstrated that pretreatment MLR can be used as a useful independent prognostic marker in patients with pulmonary LELC, and might guide us to optimize the treatment strategies. However, due to the relatively rarity of this disease and the limitation of a retrospective study, further prospective studies performed in multicenter are necessary to validate the prognostic value of MLR in pulmonary LELC.

The Frequency and Clinical Implication of ROS1 and RET Rearrangements in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Patients

To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC). The relationship between ROS1 or RET rearrangements, clinicopathological features, and prognostic factors were analyzed in resected stage IIIA-N2 NSCLC. Of the 204 cases, 4 cases were confirmed with ROS1 rearrangement, but no RET rearrangement was detected. All 4 ROS1-rearranged cases were adenocarcinomas. The predominant pathological type was acinar pattern in ROS1-rearranged tumors, except for 1 case harboring a mixture acinar and mucous tumor cells. Variants of ROS1 rearrangement were SDC4-ROS1 (E2:E32), SDC4-ROS1 (E4:E32) and SDC4-ROS1 (E4:E34). There was no significant association between ROS1 rearrangement and clinicopathological characteristics. In this cohort, multivariate analysis for overall survival (OS) indicated that squamous cell carcinoma and lobectomy were independent predictors of poor prognosis; R0 surgical resection and non-pleural invasion were independent predictors of good prognosis. In resected stage IIIA-N2 NSCLC patients, ROS1-rearranged cases tended to occur in younger patients with adenocarcinomas. The prognosis of resected stage IIIA-N2 is generally considered poor, but patients with ROS1 rearrangement will benefit from the targeted therapy.

The value of preoperative Glasgow Prognostic Score and the C-Reactive Protein to Albumin Ratio as prognostic factors for long-term survival in pathological T1N0 esophageal squamous cell carcinoma

Plenty of studies have confirmed the prognostic values of inflammation-based prognostic scores in many malignant tumors. In present study, we aim to explore whether these indexes has same prognostic values in patients with stage T1N0 esophageal squamous cell carcinoma (ESCC). The clinicopathological data of 160 consecutive patients with pathological stage T1N0 ESCC from January 2005 to December 2012 were collected retrospectively. As prognostic factors, the inflammation-based prognostic scores, including C-reactive protein (CRP), Glasgow prognostic score (GPS), prognostic index (PI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and CRP to albumin ratio (CAR), were evaluated. The best cut-off values were determined by the receiver operating characteristic (ROC) curves. The median follow-up time was 71.8 months. During the follow-up period, 34 (21.3%) patients occurred postoperative recurrence and 30 (18.8%) tumor-related deaths were recorded. The best cut-off values of CRP, NLR, PLR and CAR were 1.090, 1.976, 103.200 and 0.023, respectively. After multivariate analysis, the GPS and CAR were identified as independently prognostic factors for overall survival (OS) (p=0.017 and 0.040, respectively). Of all 160 individuals, there were 86 (53.8%) and 85 (53.1%) patients classified into high GPS group (1-2) and elevated CAR group (>0.023), respectively. In addition, the GPS were positively associated with PI (p<0.000) and the levels of serum CRP (p<0.000), NLR (p=0.004), PLR (p=0.029) and CAR (p<0.000) and the above correlations were also observed between the CAR and other inflammation-based prognostic scores (all p<0.050, except for p=0.054 for PLR levels). The preoperative GPS and CAR were simple, inexpensive, readily available predictor for long-term survival in stage T1N0 ESCC patients who underwent esophagectomy.

Overexpression of micro ribonucleic acid‐591 inhibits cell proliferation and invasion of malignant pleural mesothelioma cells

Malignant pleural mesothelioma (MPM) is an aggressive cancer refractory to current therapies. Reduced expression of micro ribonucleic acid (miR)‐591 in a range of cancer types has suggested it is a potent tumor suppressor, and overexpression has been shown to inhibit tumor cell growth. The role of miR‐591 in MPM is largely unknown.