Long-term prognosis analysis of surgical therapy for bilateral synchronous multiple primary lung cancer: a follow-up of 293 cases.

Background: Bilateral synchronous multiple primary lung cancer (BSMPLC) presents significant clinical challenges due to its unique characteristics and prognosis. Understanding the risk factors that influence overall survival (OS) and recurrence-free survival (RFS) is crucial for optimizing therapeutic strategies for BSMPLC patients. Methods: We retrospectively analyzed clinical characteristics and treatment outcomes of 293 patients with BSMPLC who underwent surgical treatment between January 2010 and July 2017. Results: The 10-year OS and RFS rates were 96.1% and 92.8%, respectively. Preoperative forced expiratory volume in 1 second (FEV1) ≥70% [hazard ratio (HR), 0.214; 95% confidence interval (CI): 0.053 to 0.857], identical pathology types (HR, 9.726; 95% CI: 1.886 to 50.151), largest pT1 (HR, 7.123; 95% CI: 2.663 to 19.055), and absence of lymphovascular invasion (LVI; HR, 7.021; 95% CI: 1.448 to 34.032) emerged as independent predictors of improved OS. Moreover, the sum of tumor sizes less than or equal to 3 cm (HR, 6.229; 95% CI: 1.411 to 27.502) and absence of pleural invasion (HR, 3.442; 95% CI: 1.352 to 8.759) were identified as independent predictors of enhanced RFS. The presence or absence of residual nodules after bilateral surgery did not influence patients' OS (P=0.987) and RFS (P=0.054). Conclusions: Patients with BSMPLC who underwent surgery generally had a favorable prognosis. Whether or not to remove all nodules bilaterally does not affect the patient's long-term prognosis, suggesting the need for an individualized surgical approach.

Intraepithelial lymphocytes promote intestinal regeneration through CD160/HVEM signaling.

Chemotherapy and radiotherapy frequently lead to intestinal damage. The mechanisms governing the repair or regeneration of intestinal damage are still not fully elucidated. Intraepithelial lymphocytes (IELs) are the primary immune cells residing in the intestinal epithelial layer. However, whether IELs are involved in intestinal epithelial injury repair remains unclear. Here, we found that IELs rapidly infiltrated the intestinal crypt region and are crucial for the recovery of the intestinal epithelium post-chemotherapy. Interestingly, IELs predominantly promoted intestinal regeneration by modulating the proliferation of transit-amplifying (TA) cells. Mechanistically, the expression of CD160 on IELs allows for interaction with herpes virus entry mediator (HVEM) on the intestinal epithelium, thereby activating downstream nuclear factor kappa (NF-κB) signaling and further promoting intestinal regeneration. Deficiency in either CD160 or HVEM resulted in reduced proliferation of intestinal progenitor cells, impaired intestinal damage repair, and increased mortality following chemotherapy. Remarkably, the adoptive transfer of CD160-sufficient IELs rescued the Rag1 deficient mice from chemotherapy-induced intestinal inflammation. Overall, our study underscores the critical role of IELs in intestinal regeneration and highlights the potential applications of targeting the CD160-HVEM axis for managing intestinal adverse events post-chemotherapy and radiotherapy.

Perioperative outcomes of bi-pigtail catheter drainage strategy versus conventional chest tube after uniportal video-assisted thoracic lung surgery.

OBJECTIVES: Chest tube (CT) drainage is a main cause of postoperative pain in lung surgery. Here, we introduced a novel drainage strategy with bi-pigtail catheters (PCs) and conducted a randomized controlled trial to compare with conventional CT drainage after uniportal video-assisted thoracic surgery lung surgery. METHODS: A single-centre, prospective, open-labelled, randomized controlled trial (ChiCTR2000035337) was conducted with a preplanned sample size of 396. The primary outcome was the numerical pain rating scale (NPRS) on the first postoperative day. Secondary outcomes included other indicators of postoperative pain, drainage volume, duration of drainage, postoperative hospital stay, incidence of postoperative complications, CT reinsertion and medical costs. RESULTS: A total number of 396 patients were randomized between August 2020 and January 2021, 387 of whom were included in the final analysis. The baseline and clinical characteristics of the patients were well balanced between 2 groups. The NPRS on the first postoperative day was significantly lower in the PC group than in the CT group (2.40 ± 1.27 vs 3.02 ± 1.39, p < 0.001), as well as the second/third-day NPRS, the incidence of sudden severe pain (9/192, 4.7% vs 34/195, 17.4%, P < 0.001) and pain requiring intervention (19/192, 9.9% vs 46/195, 23.6%, P < 0.001). In addition, the medical cost in the PC group was lower (US$7809 ± 1646 vs US$8205 ± 1815, P = 0.025). Univariable and multivariable analyses revealed that the drainage strategy was the only factor influencing the incidence of pain requiring intervention. CONCLUSIONS: The drainage strategy with bi-PCs in patients undergoing uniportal video-assisted thoracic surgery lung surgery alleviates postoperative pain with adequate safety and efficacy.

The learning curve on uniportal video-assisted thoracoscopic lobectomy with the help of postoperative review of videos.

Objectives: Video-assisted thoracoscopic lobectomy has become the preferred surgical approach in experienced centers, and uniportal approaches are becoming increasingly used. But the uniportal approach is still not widely applied presumably due to the learning difficulties of this complex procedure. The use of surgical videos may be helpful to accelerate the learning of this new techniques as in other fields. In this study, we aimed to analyze the learning curve of uniportal video-assisted thoracoscopic lobectomy with the help of postoperative review of videos. Methods: 114 patients with early-stage lung cancer who underwent uniportal video-assisted thoracoscopic lobectomy performed from 2020 to 2021 were reviewed in this study. We recorded the operation video for each patient and reviewed all the videos after surgery. The learning curves were assessed using cumulative sum analysis and the collected data of perioperative outcomes were assessed. Results: The CUMSUM curve showed its inflection points were around case 38 and 53. It was less compared with previous studies, which about 57-140 cases are needed to attain the proficient phase. The perioperative outcomes were similar in each phase, which included intraoperative blood loss (79.00 ± 26.70 vs 70.67 ± 26.64 vs 70.56 ± 27.23, p=0.0119), the length of hospital stay (3.60 ± 1.52 days vs. 3.23 ± 0.90 days vs. 3.06 ± 0.88 days, p=0.053), the rate of prolonged air leak and conversion to open thoracotomy. There was also no significant difference in the numbers and station of lymph node dissection among the three phases. Conclusions: Uniportal video-assisted thoracoscopic lobectomy is a safe and reliable approach. Recording and reviewing the operation video could help the surgeon to improve deficiencies and refine the procedure.

Impact of Lymph Node Dissection on Survival and Tumor Recurrence for Patients with Resected cT1-2N0 Small Cell Lung Cancer.

BACKGROUND: The role of lymph node (LN) dissection for early-stage small cell lung cancer (SCLC) remains unclear. Therefore, this study aimed to investigate the impact of LN dissection on patient survival and tumor recurrence for patients with cT1-2N0M0 SCLC. METHODS: Patients with cT1-2N0M0 SCLC who underwent intent-to-cure surgery at our institution between 2011 and 2019 were retrospectively reviewed. The survival outcomes of patients with systematic LN dissection (n = 112) and LN sampling (n = 35) were compared before and after propensity score-matching (PSM), as were the outcomes for patients with (pN+) and without (pN0) pathologic nodal metastasis. The prognostic impact of LN dissection was evaluated through multivariable analysis. RESULTS: The dissection group displayed significantly better overall survival (66.4% vs. 48.4%; P = 0.009) and recurrence-free survival (RFS) (63.5% vs. 37.6%;, P = 0.003) than the sampling group at 5 years. The rate of local recurrence was significantly lower in the dissection group than in the sampling group (11.6% vs. 42.9%; P < 0.001). After adjustment by multivariable analysis and PSM, LN dissection retained its independent favorable effects. The overall nodal upstaging rate was 37.6%, and the dissection group had a tendency of better RFS in both the pN0 (P = 0.05) and pN+ (P = 0.036) patients. CONCLUSION: Systematic LN dissection is associated with improved survival of patients who undergo surgery for cT1-2N0 SCLC. Further studies are warranted to verify the necessity of LN dissection in the surgery for SCLC.

Prognostic implication of isolated pulmonary nodules in patients with a history of breast cancer.

BACKGROUND: Isolated malignant pulmonary nodules were frequently seen in patients with breast cancer. These were metastasis from the breast cancer or new primary lung cancer. The role of surgery for such pulmonary nodules remains unclear. METHODS: A total of 90 patients who underwent surgery for solitary malignant pulmonary nodules between January 2010 and April 2018 after curative operation for breast cancer were reviewed. RESULTS: The pathologic diagnoses revealed 63 patients with primary lung cancer (PLC) and 27 patients with pulmonary metastatic breast cancer (MBC), which were divided into two groups. All patients were female with a mean age of 55.08 ± 9.84 years (range 31-75). Age differences between the two groups were insignificant. Of the 63 patients with PLC, 55(87%) had a lobectomy with lymphadenctomy and 8(13%) had a limited resection, while the majority of patients (78%) with MBC had a limited resection. All nodules were adenocarcinomas and their mean diameter was 1.63 ± 0.57 cm. 7/55 of patients with PLC had N1 disease while 3/6 of those with MBC had involvement of N1 nodes. For all patients, the overall survival (OS) was 86.1% at 5 years and the disease-free survival (DFS) was 86.0% at 5 years. Patients with PLC had the better surgical outcomes including OS and DFS than those with MBC did (94.2% vs. 72.8%, p = 0.017; 93.6% vs. 63.9%, p = 0.002). CONCLUSIONS: Surgical outcomes of isolated malignant pulmonary nodules in breast cancer patients were favorable. Surgery should be considered as an option for breast cancer patients with isolated pulmonary nodules.

Occult pleural dissemination detected intraoperatively in patients with thymic tumors: a retrospective analysis.

BACKGROUND: Thymic tumors usually present with adjacent organ invasion or pleural dissemination, but very few studies have reported on occult pleural dissemination detected intraoperatively. This study aimed to investigate the risk factors that can predict pleural dissemination preoperatively. METHODS: Consecutive patients with thymic tumors who underwent surgery from January 2010 to January 2017 were reviewed. Only patients without pleural dissemination detected preoperatively were included in this study. Demographic, clinical, pathological, and survival data were collected for statistical analysis. Further analyses were performed to find the risk factors of occult pleural dissemination. RESULTS: A total of 352 patients with thymic tumors were included in this study. Seven patients had pleural dissemination detected intraoperatively. All pleural dissemination cases were in clinical Masaoka-Koga stage III, and most underwent the video-assisted thoracoscopic surgery (VATS) approach (or VATS exploration). Univariate analysis showed that positive squamous cell carcinoma (SCC) antigen was the only predictor of pleural dissemination (p = 0.009). Tiny nodules close to the diaphragm were detected in the computed tomography scans of 1 case after reviewing the imaging data. Tumor recurrence occurred in 5 patients during follow-up. The disease-free survival rates were better in patients with a solitary nodule than those with multiple nodules (p = 0.019). No significant difference was detected in terms of disease-free survival rates between SCC antigen positive and SCC antigen negative patients. CONCLUSIONS: Positive SCC antigen was the only detected risk factor for predicting pleural dissemination in thymic tumors preoperatively in this study. The VATS approach (including VATS exploration) is suggested for patients with clinical Masaoka-Koga stage III and SCC antigen positive thymic tumors, according to our experience.

Clinical analyses on salvage lymphadenectomy through cervical incision for patients with cervical and cervicothoracic recurrences after esophagectomy.

BACKGROUND: Locoregional recurrences are often observed after esophagectomy with lymphadenectomy. The treatment strategy for these patients has not been established completely. The purpose of this study was to evaluate the prognosis of salvage lymphadenectomy through the cervical incision for cervical and cervicothoracic recurrences. METHODS: We retrospectively reviewed patients underwent initial esophagectomy and then salvage lymphadenectomy in Fudan University Shanghai Cancer Center during July 2006 and September 2016. Survival curve was calculated by Kaplan-Meier method. Prognostic factors for post-salvage lymphadenectomy overall survival (PSL-OS) were identified by univariate and multivariate analyses. RESULTS: The median disease-free survival (DFS) was 8 months. The median PSL-OS was 40 months (95% CI: 8.850-71.150). The 1-, 2-, 3- and 5-year PSL-OS rate were 87%, 58%, 52% and 41%, respectively. Univariate and multivariate analyses confirmed the initial TNM stage was the only independent prognostic factor for PSL-OS (P=0.000 by log-rank test, P=0.009 by Cox hazards model, HR 3.999, 95% CI: 1.413-11.316) among these patients. CONCLUSIONS: PSL survival could be considerable for patients with early initial tumor stage. Prospective studies are warranted to clarify the value of salvage lymphadenectomy.

Surgical Outcomes of Isolated Malignant Pulmonary Nodules in Patients with a History of Breast Cancer.

BACKGROUND: The role of surgery for isolated malignant pulmonary nodules in breast cancer patients remains unclear. METHODS: A total of 1286 consecutive breast cancer patients with pulmonary nodules detected by thoracic computed tomography (CT) or positron emission tomography (PET)/CT scan at Shanghai Cancer Center, Fudan University, were reviewed. Overall, 147 breast cancer patients with isolated malignant pulmonary nodules receiving surgery and/or chemotherapy were enrolled in the study. Patients were classified into three groups: patients with primary lung cancer (PLC) receiving surgery (Group 1), patients with lung metastasis receiving surgery (Group 2), and patients with lung metastasis receiving chemotherapy (Group 3). Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed for patients in all three groups, and prognostic factors for PFS for patients with pulmonary metastasis were evaluated. RESULTS: Patients with PLC receiving surgery had better survival outcomes, including OS and PFS, than patients with lung metastases who received surgical resection. Breast cancer patients with solitary lung metastasis who received metastasectomy had a significantly better PFS than those who did not; however, no statistically significant difference in OS was observed between the two groups. A multivariate analysis conducted in patients with isolated metastatic breast cancer showed that surgery was an independent factor for better PFS. CONCLUSIONS: Surgery should be considered a valid option for the diagnosis and treatment of breast cancer patients presenting with isolated malignant lung nodules.

Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma.

BACKGROUND: For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). METHODS: We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. RESULTS: A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. CONCLUSIONS: Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation.

Splenic Artery Ligation for Iatrogenic Injury in Esophagectomy Operations.

Studies have shown that splenic artery ligation without splenectomy can successfully control hemorrhage and preserve the spleen in splenic trauma. The short gastric arteries and left gastroepiploic arteries may be the most important part of the collateral blood supply to the spleen. Moreover, that the human spleen can also survive even if most of the short gastric arteries have been ligated along with the splenic artery has also been proven. Revascularization of the spleen by collateral vessels from the superior mesenteric, pancreatic, and left inferior phrenic arteries has been demonstrated by celiac angiography. Thus, splenic artery ligation could be also an alternative to splenectomy for iatrogenic spleen injury in esophagectomy operations.

[Efficacy comparison between two-field and three-field lymphadenectomy for thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To compare the safety and efficacy between three-field lymphadenectomy and normative Ivor-Lewis two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma METHODS: Clinical data of 375 patients with thoracic esophageal squamous cell carcinoma who underwent three-field lymphadenectomy(3FL) or Ivor-Lewis two-field lymphadenectomy(2FL, Ivor-Lewis) in Fudan University Shanghai Cancer Center during 2013 were retrieved and collected from electronic medical record system. Ninety-one patients received three-field lymphadenectomy (3FL group), including 16 cases of intra-cervical gastro-esophageal anastomosis and 75 cases of intra-thoracic gastro-esophageal anastomosis, while 284 patients received Ivor-Lewis two-field lymphadenectomy (2FL group) with all intra-thoracic gastro-esophageal anastomosis. Short-term outcomes were compared between two groups, including postoperative anastomotic leakage, pneumonia and respiratory failure, chylothorax, reoperation and 90-day death. Total harvested lymph nodes and positive lymph nodes in each group were also compared. A total of 338 patients were enrolled into survival analysis. Survival curve was presented by Kaplan-Meier method. RESULTS: As compared to 2FL group, the 3FL group had significantly higher ratio of N3 patients [19.8% (18/91) vs. 5.3% (15/284), P=0.000], stageIII( patients [58.2%(53/91) vs. 43.0%(122/284), P=0.007], and upper thoracic cancer patients [12.1%(11/91) vs. 3.5%(10/284), P=0.027]; also the 3FL group had more harvested lymph nodes (40.1±14.6 vs. 25.3±9.4, P=0.000) and more positive lymph nodes (3.3±4.0 vs. 1.7±3.2, P=0.000). With respect to pneumonia and respiratory failure, chylothorax, reoperation and 90-day death, no significant differences were found between the group (P=0.447, P=0.751, P=0.678, P=0.685). The 3FL group had a significantly higher incidence of anastomotic leakage than 2FL group [7.7% (7/91) vs. 1.8% (5/284), P=0.011], while its incidence of intrathoracic anastomosis leakage was 4.0% (3/75), which was not significantly different with 1.8%(5/284) of 2FL group (P=0.372). Median follow-up was 33 months. Overall 1-, 2-, 3-year survival rates were 94%, 81% and 70%, while 1-, 2-, 3-year survival rates of 3FL group were 90%, 73% and 66%, of 2FL group were 95%, 84% and 72%, respectively, without significant differences between the two group(P=0.135). Further subgroup analysis showed that no significant differences of postoperative survival in stage I(, II( and III( patients were observed between the two groups (P=0.541, P=0.511, P=0.402), meanwhile no significant differences of postoperative survival in patients with metastasis and without metastasis were found between the two groups as well (P=0.985, P=0.233). CONCLUSIONS: Three-field lymphadenectomy can be performed with acceptable perioperative morbidity and mortality. The prognosis value of three field lymphadenectomy needs further investigation. Patients with thoracic esophageal squamous cell carcinoma may have favorable survival through normative Ivor-Lewis two-field lymphadenectomy.