EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy.

OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy. RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy.

Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer.

BACKGROUND: In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC. METHODS: A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer. RESULTS: At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival. CONCLUSIONS: Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection.

Continuing surgical education of non-technical skills.

BACKGROUND: The non-technical skills for surgeons (NOTSS) system was developed as a tool to assess surgical skills for patient safety during surgery. This study aimed to develop a NOTSS-based training system for surgical trainees to acquire non-technical skills using a chest surgery scenario in a wet lab. MATERIALS AND METHODS: Trainees were categorized into three subgroups according to the years of experience as follows: Level A: 6 years or more; Level B: 3-5 years; and Level C: 1-2 years. Three stages of surgical procedure were designed: 1. chest wall resection and right upper lobe lobectomy, 2. right middle lobe sleeve lobectomy, and 3. right lower lobe lobectomy. One instructor was assigned to each operation table, who evaluated each participant's NOTSS scores consisting of 16 elements. RESULTS: When comparing average NOTSS score of all the three procedures, significant differences were observed between Level A, B, and C trainees. As an example of varying elements by procedure, Level A trainees demonstrated differences in Situation Awareness, and a significant difference was observed in Level C trainees regarding the elements of Decision Making. On the contrary, no significant difference was observed among Level B trainees. In the comparison between first-time and experienced participants, a significant improvement was observed in some elements in Level B and C trainees. CONCLUSION: This study highlights the usefulness and feasibility of the NOTSS scoring system for surgeons with different experiences and the effectiveness of providing feedback to trainees during intraoperative handoffs in a wet lab.

A case of ectopic hamartomatous thymoma: controversy over the designation.

BACKGROUND: Ectopic hamartomatous thymoma, which usually occurs in the lower neck, is a rare benign tumor containing spindle cells, epithelial nests, and adipose tissue. Although the origin of this tumor is still unknown, recent reports suggest that the designation of this tumor is inappropriate. CASE PRESENTATION: A 38-year-old with an anterior cervical mass in the suprasternal region of her neck was referred to our hospital. An ultrasound examination showed that the well-defined oval mass was 31 × 23 × 17 mm in size. A non-enhanced computed tomography scan of the neck revealed that the distinct neck mass in the subcutaneous tissue had a mixture of soft tissue and fatty components. The cervical tumor was clinically diagnosed to be an unusual lipoma with degeneration. The patient underwent the neck mass extirpation. During the surgery, the cervical mass was well demarcated and did not adhere to the surrounding tissues. The postoperative course was uneventful. The gross pathology report showed that the neck mass measured 3.0 × 2.5 × 2.0 cm. Microscopically, the tumor was composed of spindle cells, epithelial nests, and mature adipose tissue. Immunohistochemical examination revealed that both spindle cells and epithelial nests were positive for cytokeratin AE1/AE3. These histopathological findings were consistent with the features of ectopic hamartomatous thymoma. Over a follow-up period of 30 months, this patient exhibited no evidence of recurrence. CONCLUSIONS: Ectopic hamartomatous thymoma should be considered in the differential diagnosis of subcutaneous tumors in the lower neck, when the CT shows the tumor has the mixed components of fat and soft tissues.

Restrictive ventilatory impairment is associated with poor outcome in patients with cT1aN0M0 peripheral squamous cell carcinoma of the lung.

BACKGROUND: Patients with squamous cell carcinoma (SqCC) of the lung sometimes have a comorbid pulmonary disease such as pulmonary emphysema or an interstitial lung disease (ILD), both of which negatively affect patient outcome. The aim of this study was to determine the outcome of patients in a multicenter database who underwent surgery for cT1aN0M0 peripheral SqCC lung cancer. METHODS: The medical records of a total of 228 eligible patients from seven institutions were reviewed to evaluate the impact of concomitant impaired pulmonary function and other clinicopathological factors on overall survival (OS) and relapse-free survival (RFS). RESULTS: Six patients with positive or unclear tumor margins were excluded. Of the 222 remaining study patients, 42 (18.9%) and 97 (43.7%) patients were found to have coexisting restrictive or obstructive ventilatory impairment, respectively. Over a median follow-up period of 30.6 months, the 5-year OS and RFS were 69.0% and 62.6%, respectively. By multivariate analysis, ILDs identified on high-resolution computed tomography (HRCT), pulmonary function test results indicating a restrictive ventilatory impairment, and wedge resection were found to be independent risk factors for poor OS. An increased level of serum squamous cell carcinoma antigen (SCC-Ag) (>1.5 ng/mL) and the same risk factors for poor OS were independent risk factors for recurrence. Among patients who underwent anatomical lung resection (lobectomy and segmentectomy, n=173), a restrictive ventilatory impairment was an independent risk factor for poor OS, and increased serum SCC-Ag level, ILDs on HRCT, and restrictive ventilatory impairment were independent risk factors for poor RFS by multivariate analysis. Factors such as visceral pleural invasion, and lymphatic or vascular invasion were not significantly associated with outcome. CONCLUSIONS: A restrictive ventilatory impairment negatively affects the outcome of patients with cT1aN0M0 peripheral SqCC lung cancer.

Clinicopathological characteristics and lymph node metastasis pathway of non-small-cell lung cancer located in the left lingular division.

OBJECTIVES: The purpose of this study is to assess the clinicopathological characteristics of non-small-cell lung cancer (NSCLC) occurring in the left lingular division (LLD) in association with a proposal of the LLD-specific regional lymph node stations. METHODS: Medical records of patients, who underwent complete tumour resection with mediastinal lymph node dissection (MLND) for LLD-NSCLC from 2000 to 2009 in multiple institutions, were retrospectively examined. We analysed patient clinicopathological characteristics and obtained the LLD-specific regional lymph node stations, and then the validity of intraoperative navigation in lymphadenectomy for LLD-NSCLC was investigated. RESULTS: One hundred and eighty-four LLD-NSCLC patients (97 males and 87 females, and 128 adenocarcinomas and 56 non-adenocarcinomas) were studied. The 5-year overall survival (OS) and disease-free survival (DFS) rates for all LLD-NSCLC patients were 72.9 and 58.3%, respectively. We examined the lymph node metastasis patterns in 42 node-positive tumours. The frequent metastatic lymph node stations were #12u lobar node (n = 22), #5 subaortic node (n = 15) and #11 interlobar node (n = 13) in order. These three node stations were also single metastatic sites in some patients. Metastases to sub-carinal (#7) or inferior mediastinal nodes (#8) were rare. Thus, we assigned the three stations (#5, #11, #12u) as the regional lymph node stations for LLD-NSCLC. If these regional lymph node stations had been examined pathologically during surgery for a total of 160 LLD-NSCLC patients with c-T2N1M0 or lower stage disease, 125 p-N0 and 5 p-N1 patients diagnosed with no metastasis would have been subjected to selective MLND, while 14 p-N1 and all 16 p-N2 patients diagnosed with metastasis would have had complete MLND carried out. As a result, these regional lymph node stations could accurately predict the existence of p-N2 metastasis, and appropriately lead to a selective or complete MLND. CONCLUSIONS: An intraoperative pathological examination using our proposed LLD-specific regional lymph node stations may accurately diagnose the status of node metastasis, and appropriately lead to selective or complete MLND in LLD-NSCLC patients with c-T2N1M0 or lower stage disease.

One-step nucleic acid amplification for detection of lymph node metastasis in lung cancer.

OBJECTIVE: Intraoperative diagnosis of lymph node (LN) metastasis is critical in lung cancer patients. The one-step nucleic acid amplification (OSNA) assay is a novel technique using a loop-mediated isothermal amplification method of gene amplification. The objective of this study was to investigate whether the OSNA assay provides sufficient diagnosis of LN metastasis in lung cancer patients. METHODS: A total of 40 LN stations were dissected from the 20 patients, who had curative lobectomy for lung cancer. The cut halves of LNs were used for pathological diagnosis, and other halves were for the OSNA assay. The OSNA assay used cytokeratin (CK) 19 mRNA as a marker. The CK19 mRNA copy number was detected using RD-100i (Sysmex Corp., Hyogo, Japan). One formalin-fixed section with the largest cutting surface of the other halves of LNs was used for pathological examination. When discordance was observed between OSNA assay and usual pathological examination, an additional examination using 1-mm interval sections was performed. RESULTS: In the forty LN stations, three stations were diagnosed as LN metastasis positive pathologically. In these three, the OSNA assays showed extremely high numbers of CK19 mRNA copies. When the cutoff value was set to 250 copies/µl, 4 stations with relatively low copy numbers were found to be discordant. Of the 4 discordant cases, one was shown to be micro-metastasis positive in the additional pathological assessment. The sensitivity of the OSNA assay was 100.0%, and its specificity was 91.7%. CONCLUSIONS: This method could be applied to intraoperative assessment LNs metastasis.

Lung cancer complicated with IgG4-related disease of the lung.

Few have reported a concomitant malignant neoplasm with immunoglobulin G4 (IgG4)-related diseases. We describe a case of lung cancer and gastric cancer accompanied with IgG4-related disease. A 78-year-old man had an area of ground-glass opacity with central collapse in right upper lobe and a gastric cancer. The patient underwent a right upper lobectomy following a gastrectomy for the gastric cancer. Histological examination of the resected lung specimen revealed a lepidic pattern of an adenocarcinoma and a large amount of plasmacyte infiltration around the tumor. In immunohistochemical findings, the plasmacytes were stained for IgG4. Therefore, the lung tumor was considered to have associated with IgG4-related interstitial lesions.

Unexpected rapid growth of estrogen receptor positive lung cancer during pregnancy.

We report a case with lung cancer during pregnancy, which has a very poor prognosis.A 34-year old female at 30 weeks of pregnancy came to us with a cough and right lower chest pain. Chest computed tomography revealed a mass in the right lower lung lobe and the diagnosis of adenocarcinoma cT2aN1M0 was made. We performed a right sleeve pneumonectomy, as the tumor had progressed to the right main bronchus near carina. Histological sections of the specimens revealed a poorly differentiated adenocarcinoma that infiltrated surrounding structures. The pathological stage of lung cancer was T4N2M0 stage IIIB. Immunohistochemistry findings for estrogen receptor ß were positive in the nuclei of the adenocarcinoma. She had a rapid recurrence in spite of chemotherapy, and she died 7.5 months after operation. The positive estrogen receptor and hormonal condition during pregnancy might promote cancer and result in her poor prognosis.

Validity of using lobe-specific regional lymph node stations to assist navigation during lymph node dissection in early stage non-small cell lung cancer patients.

PURPOSE: The validity of our proposed lobe-specific regional lymph node stations (LSRLNS) was evaluated as a method for navigation during lymphadenectomy in patients with early stage non-small cell lung cancer (NSCLC). METHODS: A total of 725 NSCLC patients with c-T2N1M0 or less extensive disease who had undergone a curative operation with complete mediastinal lymph node dissection (MLND) were studied. The LSRLNS were #2, #3, #4 and #10 for the right upper lobe, #11i, #11s, #7 and #8 for the right lower lobe, #4, #5 and #6 for the left superior division, #11, #5 and #7 for the left lingular division and #11, #7 and #8 for the left lower lobe. RESULTS: If the LSRLNS were used for pathological examinations during surgery, 599 p-N0 and 39 p-N1 patients diagnosed with no metastasis would have been subjected to a selective MLND, while 20 p-N1 and 65 p-N2 patients who had a diagnosis of metastasis would have been navigated to a complete MLND. Two p-N2 patients with a diagnosis of no metastasis would have inappropriately undergone a selective MLND, resulting in the false negative rate at 0.3 %. CONCLUSION: Intra-operative pathological examination using our LSRLNS may accurately reveal the status of metastasis, and appropriately lead to a selective or complete MLND in patients with c-T2N1M0 or less extensive disease.

[Pulmonary mucosa-associated lymphoid tissue(MALT) lymphoma after occupational exposure to organic solvent].

A 68-year-old woman was referred to our hospital due to a left chest abnormal shadow on chest film. She had a history of occupational exposure to organic solvent for about 30 years until 10 years ago. Computed tomography (CT) scan demonstrated a nodular shadow 12 mm in diameter in the left lower lobe. As a lung cancer was suspected, partial resection of the lobe including the small lesion was performed. Since mucosa-associated lymphoid tissue(MALT) lymphoma was diagnosed by intraoperative pathological examination, we finished the operation without any more lung resection. The diagnosis was finally confirmed by histological finding of small lymphoid cell proliferation and positive staining for CD20. Chronic inflammation, such as Helicobacter pylori infection, is considered to be a cause of MALT lymphoma. We speculate that the long term exposure to organic solvent may develop the disease by continuous chemical stimulation to bronchus.

[Outcome of pulmonary resection for metastases from hepatocellular carcinoma].

Because pulmonary metastasis is considered to be systemic spread of hepatocellular carcinoma (HCC), indication of pulmonary resection as a treatment for it is not well-described. We retrospectively reviewed clinical records of the patients who underwent pulmonary resection for metastases from HCC in our hospital. Seven patients, 6 men, 1 woman, and the mean-age 65.4 year-old, underwent pulmonary resection from April in 2001 to March in 2010. During the same period, we carried out pulmonary resection for 122 patients with metastases from other malignant diseases. Therefore, pulmonary resection for HCC metastases accounted for 5.4% of the total pulmonary metastasectomy. One of the 7 patients, a 70 year-old man, survives for 69 months after right middle lobectomy for solitary HCC metastasis. Other 6 patients with multiple pulmonary metastases or with increased level of alpha-fetoprotein (AFP) before pulmonary resection died of systemic recurrence. The mean survival time of 7 patients was 20 months and was 11.8 months except the long-time survivor. From our results, patients with multiple pulmonary metastases from HCC or with increased serum level of AFP before surgery should be carefully selected as candidates for pulmonary metastasectomy.

Benefits of rib head resection via costotransverse ligament release method for T3 lung cancer in the paravertebral space.

OBJECTIVE: Lung cancer located in the paravertebral region occasionally invades the rib head (T3) and not the spine (T4). In such cases, a costotransverse ligament release (CTLR) method may be useful for complete resection without performing a vertebrectomy. METHODS: Eighteen patients with lung cancer underwent chest wall resection between 2001 and 2009 at our institutions. Of those, 7 who underwent chest wall removal with rib head resection via a CTLR method (group A) and 11 without rib head resection(conventional distal rib resection, group B) were retrospectively analyzed. RESULTS: Three patients in group A underwent induction chemoradiotherapy. All rib head resections were performed via a CTLR approach without postoperative complications. There were no deaths within 30 day in group A and 1 in group B. The mean number of resected rib heads was 2.1 in group A, while 2.0 ribs were removed in group B. There was no significant difference for operation time between groups A and B(332±112 vs. 287±114 mins, p = 0.449). Local recurrence was seen in 0 patients in group A and 3 in group B(p = 0.13). The median survival time was 1489 and 727 day, respectively, while 5-year survival rates were 0.48 and 0.41, respectively. CONCLUSION: A rib head resection via a CTLR method is an effective procedure for T3 lung cancer infiltrating the rib head.

Incidence of acute exacerbation of interstitial pneumonia in operated lung cancer: institutional report and review.

PURPOSE: Several small studies have reported that acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection for patients with non-small cell lung cancer, though the incidence rate is unclear. METHODS: We examined our institutional data and performed a search of the MEDLINE database for publications regarding AE of IIP following surgery for lung cancer. Studies reporting the incidence rates of IIP and AE were included. RESULTS: Eleven studies including our institutional data were determined to be eligible. Seven studies designated the incidence of IIP. Of 4749 patients (from 7 studies) who underwent lung resection for NSCLC, 277 had IIP, for an incidence rate of 5.8% (range 1.1%-11.7%). Eleven studies designated the incidence of AE from IIP patient, 67 (15.8%) of 424 IIP patients (from 11 studies) developed AE after surgery, of whom 38 (56.7%) died during the postoperative course. CONCLUSION: Coexistent IIP in patients with lung cancer increases the risk of lung cancer surgery. Furthermore, AE of IIP may be a major cause of operation-related death.

A case of Mullerian cyst arising in posterior mediastinum.

A mediastinal Mullerian cyst was initially reported as a new category of congenital cyst by Hattori, et al. in 2005. We treated a 53-year-old female referred to us with a posterior mediastinal tumor found at the Th5 prevertebral level by chest-computed tomography during a medical check-up. She had a history of mediastinal teratoma, which was removed at the age of 35. Chest magnetic resonance imaging revealed homogenous, high-intensity signals in T2-weighted images. The lesion was resected using a thoracoscopic procedure, and histologic and immunohistochemical staining revealed a ciliated cyst of Mullerian origin. The newly established mediastinal Mullerian cyst should be included in the differential diagnosis of posterior mediastinal cysts.

[Diaphragmatic metastasis from uterine corpus cancer].

We report a case of metastatic diaphragm tumor from uterine corpus cancer. A 72-year-old female had a tumor on right diaphragm 4-years after operation for uterine corpus cancer. After chemotherapy, tumor resection was performed by right lung basal segmentectomy, partial liver resection, and partial diaphragm resection. The pathological examination revealed adenocarcinoma, compatible with uterine corpus cancer, metastasizing in diaphragm and involving lung and liver. After the operation, a local recurrence occurred at parasternal lymph node, which is considered to be present on the efferent route of lymph flow from diaphragm.

[Radical resection following to concurrent chemoradiotherapy for eighty-five year-old patient with superior sulcus tumor].

An 85-year-old male with superior sulcus tumor was referred to our hospital complaining right brachial pain and omalgia. Chest computed tomography showed right apical lung tumor involving the 1st rib, and bronchoscopy established a diagnosis of squamous cell carcinoma, cT3NOM0. After concurrent chemoradiotherapy [cisplatin (CDDP) + 60 Gy], functional examination indicated him to be tolerable to lobectomy, and he underwent right upper lobectomy + chest wall resection (1st-3rd ribs) + lymph-node dissection. Pathological examination revealed that the effect of chemoradiotherapy was Ef. 3. The postoperative course was uneventful. He is free from recurrence for 7 years after the surgery.

A rare cause of dysphagia: malignant pleural mesothelioma in the posterior mediastinum.

A 69-year-old man presented to the emergency room with dysphagia and vomiting. A computed tomographic scan revealed a posterior mediastinal mass surrounding the lower portion of the esophagus. Endoscopic examination demonstrated narrowing of the lower esophagus without malignant mucosal lesions. Thoracoscopic biopsies of the mediastinal mass failed to yield a pathologic diagnosis. The hyaluronic acid concentration in the left pleural effusion was remarkably high (755 mg/L), which is a finding strongly suggestive of malignant mesothelioma. Four months after the initial admission, a subcutaneous nodule was found in the left chest wall and a biopsy was taken. The histopathologic and immunohistochemical findings of the biopsy were consistent with the diagnosis of pleural malignant mesothelioma.