Pulmonary Vein Stump Thrombosis and Cerebral Infarction after Left Upper Lobectomy.

BACKGROUND: Pulmonary vein stump thrombosis may occur after left upper lobectomy (LUL) and is a potential risk factor for cerebral infarction. However, there are few reports on the role of pulmonary vein stump thrombosis in the development of cerebral infarction. We aimed to clarify the correlation between pulmonary vein stump thrombosis and cerebral infarction following LUL. METHODS: We evaluated 296 patients who underwent contrast-enhanced computed tomography (CT) after LUL for lung cancer at the Shizuoka Cancer Center Hospital in Shizuoka, Japan, between September 2002 and December 2015. The cerebral infarction in patients with pulmonary vein stump thrombosis was examined, and the risk factors for cerebral infarction were identified via a univariate analysis of the clinicopathological and surgical variables. RESULTS: Overall, 179 men and 117 women (median age: 68 years; range: 36-88 years) were included. The median observation period was 68 months. Pulmonary vein stump thrombosis occurred in 21 (7%) patients and cerebral infarction occurred in 15 (5%) patients. None of the 21 patients with pulmonary vein stump thrombosis developed cerebral infarction. Most cerebral infarctions (12/15) were diagnosed in the late phase (> 3 months). The pathological stage of cancer was found to be the only significant risk factor for cerebral infarction by the univariate analysis. CONCLUSION: Pulmonary vein stump thrombosis following LUL was not necessarily associated with cerebral infarction, including the late phase. A prospective observational study with contrast-enhanced chest CT would be required to investigate the risk factors for cerebral infarction in each phase of the postoperative period.

Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model.

Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.

Radiotherapy for local recurrence of non-small-cell lung cancer after lobectomy and lymph node dissection-can local recurrence be radically cured by radiation?

BACKGROUND: There is no standard therapeutic approach for local recurrence of non-small cell lung cancer (NSCLC) after complete resection. We investigated the outcomes of radiotherapy (RT) for patients with local recurrence. METHODS: We reviewed 46 patients who underwent curative-intent RT for local recurrence after lobectomy or pneumonectomy accompanied with mediastinal lymph node dissection between 2002 and 2014. We analyzed overall survival (OS), progression-free survival (PFS), local control, tumour response and the re-recurrence pattern. RESULTS: Among the 46 patients, 16 received concurrent chemotherapy. The median follow-up period was 48 months. The response rate was 91%. The 5-year OS and local control rates were 47.9 and 65.3%, respectively, and the 5-year PFS rate was 22.8%. Female sex and complete response to radiation were favourable prognostic factors. Of the 33 patients with recurrence after radiation, 32 (97%) had distant metastasis. CONCLUSIONS: Although RT for local recurrence has high efficacy, distant relapse after radiation remains a major issue. Therefore, combination systemic therapy for local recurrence at any site should be further investigated. Since it is difficult to achieve a radical cure for local recurrence using RT, further study, for the administration of post-operative adjuvant therapy, is recommended.

Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

BACKGROUND AND OBJECTIVE: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. METHODS: The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. RESULTS: Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. CONCLUSION: Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values.

[Trial of the New Pain Assessment after Thoracic Surgery].

We evaluated postoperative pain intensity using the PainVision system for quantitative pain analysis and assessed the correlation with numerical rating scale( NRS) for subjective pain evaluation. Twelve patients were evaluated for both pain intensity by PainVision and values by NRS at 6, 24 and 48 hours following after thoracic surgery. The correlation coefficient between pain intensity and NRS values was 0.20, which suggested that degrees of pain measured by subjective and quantitative pain scales were not necessarily consistent. Assessing pains with both conventional subjective pain evaluation and quantitative pain intensity evaluation by PainVision is possibly useful in providing optimal postoperative pain management.

[Thoracic Paravertebral Block in Patients Ineligible for Epidural Block].

We retrospectively assessed the effectiveness and the safety of thoracic paravertebral block(PVB) in patients ineligible for epidural block (EP). Eleven PVB patients and 33 EP patients were enrolled. Postoperative pain was evaluated using a numerical rating scale (NRS). The mean NRS ± standard deviation at rest 24 and 48 hours after surgery were 1.36 ± 1.63 and 0.55 ± 1.03 in the PVB group and 1.07 ± 1.47 and 1.38 ± 1.31 in the EP group, respectively. There were no statistically significant differences in the NRS scores. Approximately 10% of the EP patients had complications such as hypotension, nausea and vomiting, or urinary retention. On the other hand, there were no adverse events in the PVB group. PVB can provide pain relief comparable to EP with a better side-effect profile. There were no technical complications associated with PVB. Thoracic PVB is an effective and safe method of postoperative analgesia for patients undergoing thoracic surgery with ineligibilities for EP.

Association between recovery from desaturation after stair climbing and postoperative complications in lung resection.

OBJECTIVE: The stair-climbing test (SCT) is used as a surrogate for cardiopulmonary exercise testing, which measures maximal oxygen uptake, and considered a useful method for assessing exercise capacity in thoracic surgery. This study aims to investigate whether the recovery time of percutaneous oxygen saturation (SpO2) after stair climbing is a predictor of postoperative complications after lobectomy. METHODS: We retrospectively identified 54 patients who performed SCT and underwent lobectomy between January 2015 and February 2023 at Shizuoka Cancer Center. The SpO2 recovery time was defined as the time required to recover from the minimum to resting value after stair climbing. The association between SpO2 recovery time and early postoperative pulmonary complications within 30 days after surgery was analyzed. RESULTS: Eleven patients (20.4%) had postoperative pulmonary complications (≥ Clavien-Dindo Classification Grade 2). The cutoff value of SpO2 recovery time obtained from the receiver operating characteristic curve analysis was 90 s [sensitivity, 81.8%; specificity, 72.1%; AUC, 0.77 (95% confidence interval, 0.64-0.90)]. The occurrence of postoperative pulmonary complications was 42.9% in the delayed recovery time (DRT; SpO2 recovery time ≥ 90 s) group and 6.1% in the non-DRT (SpO2 recovery time < 90 s) group (p = 0.002). DRT was a predictor of postoperative pulmonary complications (odds ratio, 11.60; 95% CI 2.19-61.80). CONCLUSIONS: DRT of SpO2 after stair climbing is a predictor of postoperative pulmonary complications following lobectomy in borderline patients who require exercise capacity assessment. SpO2 monitoring after stair climbing may be useful as one of the preoperative assessments in patients undergoing lobectomy.

Brain Metastasis of Non-small Cell Lung Cancer After Disease-Free Survival of 5 years: Case Series and Comprehensive Literature Review.

BACKGROUND: In the treatment of nonsmall cell lung cancer (NSCLC), a disease-free survival of 5 years is a criterion for cure. This study aimed to evaluate the characteristics and outcomes of patients with brain metastases of NSCLC after a disease-free survival of 5 years (late recurrent brain metastasis [LRBM]). METHODS: We reviewed 1281 consecutive patients with brain metastasis of lung cancer at a single institute between November 2014 and December 2022. Relevant articles were retrieved from PubMed. Only peer-reviewed journals published in English were included. RESULTS: Six patients (0.47%) showed LRBM. Three were male. The median age at lung cancer diagnosis was 45 years. The histological diagnosis of all patients was adenocarcinoma. Driver gene mutations were observed in five patients. The median latency period from lung cancer treatment to the development of brain metastasis was 13 years. All patients had no metastasis to any other organs and underwent craniotomies. The median follow-up duration after craniotomy was 3.5 years. No local intracranial recurrences were observed. Three patients had distant intracranial recurrences at 7, 2, and 0.6 years after craniotomy. Five patients survived for 8, 4, 3, 2, and 0.3 years after craniotomy. One patient experienced re-recurrence in the lung 4 years after craniotomy and died 3.7 years later. In our systematic review, only six studies described LRBM of NSCLC. CONCLUSIONS: LRBM is rare in patients with NSCLC. In our institution, many of these patients harbored driver gene mutations, and achieved long-term survival with aggressive local therapy. Multicenter analysis is mandatory.

Injectable extracellular matrix hydrogels contribute to native cell infiltration in a rat partial nephrectomy model.

Decellularized extracellular matrix (dECM) hydrogels have cytocompatibility, and are currently being investigated for application in soft tissues as a material that promotes native cell infiltration and tissue reconstruction. A dECM hydrogel has broad potential for application in organs with complex structures or various tissue injury models. In this study, we investigated the practical application of a dECM hydrogel by injecting a kidney-derived dECM hydrogel into a rat partial nephrectomy model. The prepared dECM hydrogel was adjustable in viscosity to allow holding at the excision site, and after gelation, had an elastic modulus similar to that of kidney tissue. In addition, the migration of renal epithelial cells and vascular endothelial cells embedded in dECM hydrogels was observed in vitro. Four weeks after injection of the dECM hydrogel to the partial excision site of the kidneys, infiltration of renal tubular constituent cells and native cells with high proliferative activity, as well as angiogenesis, were observed inside the injected areas. This study is the first to show that dECM hydrogels can be applied to the kidney, one of the most complex structural organs and that they can function as a scaffold to induce angiogenesis and infiltration of organ-specific renal tubular constituent cells, providing fundamental insights for further application of dECM hydrogels.

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis.

Cell transplantation using mesenchymal stem cells (MSCs) has emerged as a promising approach to repairing and regenerating injured or impaired organs. However, the survival and retention of MSCs following transplantation remain a challenge. Therefore, we investigated the efficacy of co-transplantation of MSCs and decellularized extracellular matrix (dECM) hydrogels, which have high cytocompatibility and biocompatibility. The dECM solution was prepared by enzymatic digestion of an acellular porcine liver scaffold. It could be gelled and formed into porous fibrillar microstructures at physiological temperatures. MSCs expanded three-dimensionally in the hydrogel without cell death. Compared to the 2-dimensional cell culture, MSCs cultured in the hydrogel showed increased secretion of hepatocyte growth factor (HGF) and tumor necrosis factor-inducible gene 6 protein (TSG-6), both of which are major anti-inflammatory and anti-fibrotic paracrine factors of MSCs, under TNFα stimulation. In vivo experiments showed that the co-transplantation of MSCs with dECM hydrogel improved the survival rate of engrafted cells compared to those administered without the hydrogel. MSCs also demonstrated therapeutic effects in improving inflammation and fibrosis of pancreatic tissue in a dibutyltin dichloride (DBTC)-induced rat pancreatitis model. Combinational use of dECM hydrogel with MSCs is a new strategy to overcome the challenges of cell therapy using MSCs and can be used for treating chronic inflammatory diseases in clinical settings.

Retention index of FDG-PET/CT SUVmax of the primary tumor in non-small cell lung cancer as a predictor of lymph node metastasis: a retrospective study.

BACKGROUND: Accurate staging of non-small cell lung cancer is key in treatment planning and prediction of prognosis. We investigated the correlation between the maximum standardized uptake value (SUVmax) retention index (RI) of the primary tumor and lymph node metastasis in non-small cell lung carcinoma. We also evaluated the tendencies according to the histological types. METHODS: We retrospectively evaluated 218 non-small cell lung cancer (NSCLC) tumors from 217 patients who underwent preoperative fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) followed by lung surgery and lymph node resection between July 2015 and August 2020. All primary tumors were calculated as the SUVmax at 50 min (SUVmaxearly [SUVmaxe]) and 120 min (SUVmaxdelayed [SUVmaxd]), and RI. The clinicopathological factors of interest were compared based on lymph node metastasis status and NSCLC histopathological subtype. RESULTS: The median SUVmaxe and SUVmaxd of the primary tumors were 3.3 and 4.2, respectively, and the median RI was 0.25. The RI was significantly higher in the pN(+) (n = 44) group (0.30) compared to the pN0 (n = 174) group (0.24) (p = 0.01). In patients with adenocarcinoma (n = 145), the RI was also significantly higher in the pN(+) (n = 29) group (0.29) compared to the pN0 (n = 116) group (0.16) (p < 0.01). A high RI of the primary tumor was an independent risk factor for lymph node metastasis, particularly in patients with adenocarcinoma (odds ratio: 12.30, p < 0.05). CONCLUSIONS: The RI of primary NSCLC tumors can help predict lymph node metastases, particularly in patients with adenocarcinoma.

Lobe-specific nodal dissection with intraoperative frozen section analysis for clinical stage-I non-small cell lung cancer: a validation study by propensity score matching.

OBJECTIVE: Lobe-specific nodal dissection (LND) is increasingly used for non-small cell lung cancer (NSCLC) in Japan; however, its treatment validity remains unclarified. Since 2013, LND has been used as a standard procedure for clinical stage-I (c-stage-I) NSCLC at our institution. We aimed to evaluate its validity using intraoperative frozen section analysis (FSA) for c-stage-I NSCLC. METHODS: The participants comprised patients with NSCLC who underwent LND between 2013 and 2016 (n = 307) or systematic nodal dissection (SND) between 2002 and 2013 (n = 367) for c-stage-I disease. FSA was routinely performed in LND to examine at least three stations. Outcomes were compared between the LND and SND groups. Patients in whom LND was converted to SND due to metastasis on FSA of the sampled lymph node were still categorized into the LND group, i.e., intention-to-treat analysis. The prognostic impact was compared using propensity score matching. RESULTS: The rate of conversion from LND to SND was 10.4%. Of the patients converted to SND, 12.5% had metastases outside the LND area. False-negative N2 results were detected in only 0.7% of the LND group patients after FSA. After matching, each group had 220 patients. There were no significant between-group differences in the lymph-node recurrence rate (7% vs. 6%), 5-year recurrence-free survival (80.1% vs. 79.0%), and overall survival (90.4% vs. 90.3%). CONCLUSIONS: LND with intraoperative FSA is a valid modality that could serve as a standard surgical procedure for c-stage-I NSCLC. Intraoperative FSA may lower the residual lymph-node metastasis risk in LND.

Chylothorax after pulmonary resection and lymph node dissection for primary lung cancer; retrospective observational study.

BACKGROUND: Pulmonary resection with mediastinal lymph node dissection for treating primary lung cancer could sometimes causes chylothorax as a postoperative complication. This study examined the validity of treatments for chylothorax in our hospital. METHODS: We evaluated 2019 patients who underwent lobectomy, bilobectomy, or pneumonectomy with mediastinal lymph node dissection for primary lung cancer at Shizuoka Cancer Center Hospital, Shizuoka, Japan, between September 2002 and March 2018. The diagnostic criteria for postoperative chylothorax were that the drainage from the pleural drain was evidently white and turbid, or the pleural effusion contained a triglyceride level of > 110 mg/dL. The clinical courses and treatments were retrospectively reviewed. RESULTS: Postoperative chylothorax occurred in 37 patients (1.8%), 20 men and 17 women, with a median age of 70 years (33-80). A low-fat diet was instituted to all patients; 35 cases improved with conservative treatment, and 2 cases required reoperation. Nine cases had a drainage volume ≥ 500 mL one day following the low-fat diet commencement, which was resolved with conservative treatment and decreased drainage was observed on the third day of treatment in seven of those cases. Two cases with excessive drainage of ≥ 1000 mL in one day and systemic symptoms associated with chyle loss needed surgery. CONCLUSIONS: Even when the daily drainage volume exceeds 500 mL following a low-fat diet, there were many cases that could be cured conservatively. The indication for surgery needs to be carefully considered.

Validity of surgical decision based on intraoperative frozen section diagnosis for unconfirmed pulmonary nodules with previous malignancy.

OBJECTIVES: The lung is a major target organ of metastasis in several cancers. To distinguish primary lung cancer from pulmonary metastases is a clinical challenge. Small pulmonary nodules (PNs) are frequently diagnosed by frozen section diagnosis (FSD) intraoperatively after resection. Intraoperative FSD is very important to determine the extent of subsequent surgical procedures. This study aimed to know the validity of surgical decision based on FSD for preoperatively unconfirmed PN with previous malignancy. METHODS: We retrospectively evaluated 96 patients with suspected malignant PN who underwent intraoperative FSD between 2018 and 2020. Intraoperative FSD, final diagnosis, and surgical procedure data were examined. RESULTS: Surgical procedure adequacy, based on FSD for preoperatively unconfirmed PN with previous malignancy, was 91% (88/96). The overall diagnostic accuracy of FSD was 83.3% (80/96). Discrepancy was noted in two cases (2.1%), and conclusive diagnosis could not be reached intraoperatively in 14 cases (14.6%). A second surgery was required in three patients and no additional excision for primary lung cancer was performed in three patients. Conversely, there were three cases of over-surgery, namely, lobectomy for pulmonary metastasis. CONCLUSIONS: Surgical decision-making based on FSD for preoperatively unconfirmed PN in patients with previous malignancy was generally adequate. However, there were inadequate or excessive surgical procedures due to limitations in the accuracy of intraoperative FSD. Improving the accuracy of intraoperative FSD is a necessary step for obtaining adequate surgical decision-making and precision medicine.

Quantitative severity of emphysema is related to the prognostic outcome of early-stage lung cancer.

OBJECTIVES: Although pulmonary emphysema is a component of chronic obstructive pulmonary disease, the prognostic significance of the quantitative severity of emphysema in patients with primary lung cancer is unclear. This study aimed to identify the association between the quantitative severity of emphysema detected by the low-attenuation area on computed tomography and the prognostic outcome of early non-small-cell lung cancer. METHODS: A consecutive series of 1062 patients who underwent lobectomy for clinical stage I and II non-small-cell lung cancer were enrolled in this study. The clinicopathological features and long-term outcomes of patients with primary lung cancer in emphysema were investigated. The extent of emphysema in the lobe where the tumour was present was measured by preoperative computed tomography as a percentage of the low-attenuation area (LAA%). RESULTS: LAA% ≥ 1.0% was detected in 145 (13.7%) patients. LAA% was associated with pleural invasion (P < 0.0001), vascular invasion (P < 0.0001) and a larger tumour size (P = 0.001). The overall survival and recurrence-free survival in patients with LAA% ≥ 1.0% and with LAA% < 1.0% at 5 years were 78.6% and 92.1% (P < 0.0001) and 68.7% and 85.2% (P < 0.0001), respectively. According to the Cox proportional hazards model, LAA% was an independent prognostic factor for overall survival and recurrence-free survival (P = 0.0004 and P = 0.003, respectively). CONCLUSIONS: The quantitative severity of pulmonary emphysema was found to be associated with poor prognosis and clinicopathological aggression in early non-small-cell lung cancer.

An organ-derived extracellular matrix triggers in situ kidney regeneration in a preclinical model.

It has not been considered that nephrons regenerate in adult mammals. We present that an organ-derived extracellular matrix in situ induces nephron regeneration in a preclinical model. A porcine kidney-derived extracellular matrix was sutured onto the surface of partial nephrectomy (PN)-treated kidney. Twenty-eight days after implantation, glomeruli, vessels, and renal tubules, characteristic of nephrons, were histologically observed within the matrix. No fibrillogenesis was observed in the matrix nor the matrix-sutured kidney, although this occurred in a PN kidney without the matrix, indicating the structures were newly induced by the matrix. The expression of renal progenitor markers, including Sall1, Six2, and WT-1, within the matrix supported the induction of nephron regeneration by the matrix. Furthermore, active blood flow was observed inside the matrix using computed tomography. The matrix provides structural and functional foundations for the development of cell-free scaffolds with a remarkably low risk of immune rejection and cancerization.

Decellularized Organ-Derived Scaffold Is a Promising Carrier for Human Induced Pluripotent Stem Cells-Derived Hepatocytes.

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research.

Peritoneal dissemination of pancreatic cancer caused by endoscopic ultrasound-guided fine needle aspiration: A case report and literature review.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity. Although needle-tract seeding caused by EUS-FNA has been recently reported, dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis. However, the frequency of dissemination and needle-tract seeding appears to have been underestimated. We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA. CASE SUMMARY: An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening. Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma; hence laparoscopic distal pancreatectomy with lympha-denectomy was performed. No intraoperative peritoneal dissemination and liver metastasis were visually detected, and pelvic lavage cytology was negative for carcinoma cells. The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin; however, pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site, and the cells were suspected to be disseminated via EUS- FNA. Hence, the patient received adjuvant therapy with S-1 (tegafur, gimeracil, and oteracil potassium); however, computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis. The patient received palliative therapy and died 8 mo after the operation. CONCLUSION: The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination, especially for cancers in the pancreatic body or tail.

Impact of Positive Pleural Lavage Cytology for Each Stage of Non-Small Cell Lung Cancer Patients.

BACKGROUND: Positive preresection pleural lavage cytology (PLC+) is a poor prognostic factor in non-small cell lung cancer (NSCLC). This study evaluated the prognostic value of PLC+ for the different pathologic stages (p-stages) of NSCLC. METHODS: A retrospective analysis was conducted of all 1293 staged patients who underwent curative resection in the Shizuoka Cancer Center Hospital, Shizuoka, Japan, for NSCLC to evaluate the impact of PLC+ on survival, specifically in patients with p-stage I NSCLC. The survival rate between patients with and without PLC+ was compared using the Kaplan-Meier method with the log-rank test for comparison. RESULTS: PLC+ was identified in 50 of the 1293 patients (3.9%) and was correlated with lymph node metastasis (P < .001), a pathologic tumor size larger than 3 cm (P = .033), the presence of pleural invasion (P < .001), and adenocarcinoma (P = .038). In patients with PLC+, the 5-year disease-free survival (DFS) was 31.1%, compared with 75.7% for patients with a negative PLC (PLC-) (P < .001). On multivariate analysis, the PLC+ status was an independent prognostic factor of DFS (hazard ratio 1.70; P = .013). Among the 818 patients with p-stage I NSCLC, PLC+ was identified in 22, with a 5-year DFS of 40.4%. The prognosis in patients with p-stage I NSCLC with PLC+ was equal to that in patients with p-stage IIIA NSCLC with PLC- (5-year DFS, 40.4% and 39.0%). CONCLUSIONS: PLC is an independent prognostic factor in early-stage NSCLC. Therefore, it may be appropriate to up-stage an NSCLC diagnosis in the presence of PLC+, especially for patients with p stage I.

Bronchial intraepithelial recurrence of a pulmonary large cell neuroendocrine carcinoma.

INTRODUCTION: We encountered a case of a large cell neuroendocrine carcinoma with bronchial intraepithelial spread, a unique form of recurrence. PRESENTATION OF CASE: A 63-year-old man underwent middle lobectomy and systematic lymph node dissection for lung cancer. The pathological diagnosis was a large cell neuroendocrine carcinoma, and the pathological stage of the tumor was T2aN0M0, stage IB. At 30 months after surgery, the patient complained of continuous cough, and computed tomography revealed a thickened right upper bronchus. Transbronchial biopsy revealed a large cell neuroendocrine carcinoma with bronchial intraepithelial recurrence. The patient died of disease 24 months after recurrence was diagnosed. DISCUSSION: In cases of centrally located small cell lung carcinoma, it is well known that tumor cells progress along the sub-bronchial mucosa. In contrast, the mechanism of tumor progression of large cell neuroendocrine carcinoma is not fully elucidated because of the rarity of such cases. Endobronchial metastases usually show the presence of polypoid lesions. To the best of our knowledge, this is the first case of endobronchial metastasis from a pulmonary large cell neuroendocrine carcinoma showing bronchial intraepithelial recurrence. CONCLUSIONS: Clinicians should be aware of this unique form of recurrence in patients with large cell neuroendocrine carcinoma of the lungs.