Adherence and feasibility of 2 treatment schedules of S-1 as adjuvant chemotherapy for patients with completely resected advanced lung cancer: a multicenter randomized controlled trial.

BACKGROUND: We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients. METHODS: Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival. RESULTS: From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1-3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94). CONCLUSIONS: The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1-3 elevation of bilirubin. TRIAL REGISTRATION: This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

Prognostic factors after pulmonary metastasectomy for colorectal cancer and rationale for determining surgical indications: a retrospective analysis.

OBJECTIVE: We aimed to identify prognostic factors after pulmonary metastasectomy for colorectal cancer and propose the clinical application of them. Furthermore, we endeavored to provide a rationale for pulmonary metastasesectomy. BACKGROUND: Several prognostic factors have been proposed, but clinical application of them remains unclear. Moreover, there is no theoretical evidence that pulmonary metastasectomy is indicated for colorectal cancer. METHODS: We retrospectively analyzed 1030 patients who underwent pulmonary metastasectomy for colorectal cancer from 1990 to 2008. Prognostic factors were identified and the relationship of recurrent sites after pulmonary resection to pulmonary tumor size was assessed. RESULTS: Overall 5-year survival was 53.5%. Median survival time was 69.5 months. Univariate analysis showed tumor number (P < 0.0001), tumor size (P < 0.0001), prethoracotomy serum carcinoembryonic antigen (CEA) level (P < 0.0001), lymph node involvement (P < 0.0001), and completeness of resection (P < 0.0001) to significantly influence survival. In multivariate analysis, all remained independent predictors of outcome. In patients whose recurrent sites extended downstream from the lung via hematogenous colorectal cancer spread, pulmonary tumor size was significantly larger than in those with recurrent sites confined to the lung and regions upstream from the lung. CONCLUSIONS: We should utilize these prognostic factors to detect patients who might benefit from surgery. Therefore, we should periodically follow up advanced colorectal cancer patients by chest computed tomography to detect small pulmonary metastases before serum CEA elevation. Metastases to the lung or organs upstream from the lung are regarded as semi-local for colorectal cancer. This concept provides a rationale for validating surgical indications for pulmonary metastases from colorectal cancer.

Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma.

A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.

[A case with an aberrant systemic arterial supply to the basal lung diagnosed by three-dimensional computed tomography and successfully treated with surgical resection of an aberrant artery].

A 21-year-old man was admitted to our hospital complaining of recurrent hemoptysis. Computed tomography revealed ground-glass opacities in the right lower lung field, and three-dimensional computed tomography (3D-CT) demonstrated an aberrant artery which originated from the descending aorta and supplied the right S10b. Bronchoscopy showed no evidence of intraluminal bleeding or bronchial branching abnormalities. The patient was given a diagnosis of aberrant systemic arterial supply to the right normal basal segment of the lung (Pryce type I). Since the affected area, supplied from an aberrant systemic artery, was very small with no abnormalities in the lung parenchyma, the patient underwent a single resection of the aberrant artery via video-assisted thoracoscopy (VATS) without segmentectomy. The patient remained free of hemoptysis during 5 months follow-up after the operation.

Long-term survival of airway silicone stents in patients with central airway stenosis or obstruction due to thoracic malignancy.

OBJECTIVES: Silicone airway stents are used to manage central airway stenosis or obstruction, although their impact on long-term survival remains unknown in patients with central airway stenosis or obstruction due to thoracic malignancy. In this study, we retrospectively analyzed the impact of silicone stents on survival. METHODS: We retrospectively analyzed clinical data of 106 patients with central airway stenosis or obstruction due to thoracic malignancy treated by stenting at Toho University Omori Medical Center between 1998 and 2018. RESULTS: Patients treated with silicone stents had significantly higher survival rates than patients treated with metallic stents (p = 0.0173). Silicone stents patients also had significantly more additional treatments for thoracic malignancy after stenting than metallic stents patients (p = 0.0007). Notably, significantly more silicone stents patients underwent chemoradiotherapy or radiotherapy (p = 0.0268, p = 0.0300). During multivariate analyses, the additional treatment, including chemoradiotherapy or radiotherapy, was an independent optimal prognostic factor. CONCLUSIONS: Silicone stents patients had significantly higher survival rates than metallic stents patients. Although stenting for airway stenosis or obstruction due to thoracic malignancy may be mainly palliative, additional treatments after stenting should be considered to improve the prognoses of patients with airway stenosis or obstruction due to thoracic malignancy.

Contributions of Airway Stent for Long-term Outcome in Patients With Malignant Central Airway Stenosis or Obstruction.

BACKGROUND: Although an airway stent is used for malignant central airway stenosis or obstruction, long-term outcomes are unknown. In this study, we retrospectively analyzed the clinical features of patients who required stenting for malignant central airway stenosis or obstruction. PATIENTS AND METHODS: We retrospectively analyzed clinical data from 116 patients with stenting for central airway stenosis or obstruction who underwent treatment at Toho University Hospital from 1998 to 2018. We evaluated the clinical features, prognoses, and complications for stenting in these patients. RESULTS: The distribution of the 116 patients was as follows: lung cancer, 53; esophageal cancer, 40; thyroid cancer, 8; and others, 15. Patients with thyroid cancer had a significantly higher rate of complications after stenting than patients with lung cancer (P=0.0062), esophageal cancer (P=0.0029), and others (P=0.0062). Patients with esophageal cancer had a significantly worse prognosis than patients with lung and thyroid cancer. In patients with lung cancer the prognosis was significantly different between patients who underwent additional treatment for lung cancer after stenting and patients with no treatment (P=0.0398), and patients who received chemoradiotherapy for lung cancer after stenting had a significantly better prognosis than patients with no treatment (P=0.0306). CONCLUSION: Stenting for airway stenosis/obstruction may improve prognosis in patients with lung or thyroid cancer, especially if patients with lung cancer undergo additional treatments after stenting, although airway stenting for patients with esophageal cancer was palliative. New treatment strategies may be necessary for patients with esophageal cancer after stenting to improve prognosis.

[The role of positron emission tomography in the detection of incidental gastrointestinal tract lesions in patients examined for lung cancer].

The purpose of this study was to clarify the clinical characteristics of lung cancer patients with abnormal accumulation in the gastrointestinal tract by fluoro-2-deoxyglucose positron emission tomography (PET). Of the 968 consecutive patients with primary lung cancer who underwent PET from October 2005 through September 2009, 26 patients had local abnormal accumulation in the gastrointestinal tract. We retrospectively compared the localization of abnormal accumulation in the gastrointestinal tract, standardized uptake value (SUV) max (1 hour), and the final clinical diagnosis. The site of abnormal accumulation was the esophagus in 1 case, the stomach in 8 and the small intestine to large intestine in 17. In 15 out of 26 (57%) cases with true PET positive results, there was esophageal cancer in 1 case, gastric cancer in 2, gastrointestinal stromal tumor in 1, colon cancer in 8, and 1 each of metastasis to the stomach, small intestine and large intestine from lung cancer. In 11 cases with false PET-positive results, there was a stomach polyp in 1 case, gastritis in 3, colon polyp in 1, diverticulitis in 1 and normal physiologic accumulation in 5. There were no differences in mean SUV max among malignant lesions, benign lesions, and normal physiologic accumulation. We should perform endoscopy of the digestive tract to detect malignant lesions with high incidence rates when PET shows localalized abnormal accumulation in the gastrointestinal, tract in patients with lung cancer.

Usefulness of fluoro-2-deoxyglucose positron emission tomography for investigating unexplained rising carcinoembryonic antigen levels that occur during the postoperative surveillance of lung cancer patients.

BACKGROUND: Positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) has been useful for the detection of recurrent lung cancer. However, such technology is expensive and is not always widely available. In this study, we evaluated the selected use of FDG-PET for lung cancer patients with re-elevated levels of serum carcinoembryonic antigen (CEA) after curative surgery. METHODS: Among 327 patients who underwent curative resection for primary lung cancer from May 2002 through March 2007, 199 had adenocarcinoma, of whom 78 (39%) had elevated levels of serum CEA before treatment. After surgery, the level was monitored every 1 to 3 months. Re-elevation of CEA was recognized in 39 (50%) patients, 22 of whom underwent FDG-PET and were included in this study. FDG-PET images were visually inspected, and abnormally increased FDG uptake was interpreted as recurrence. The sensitivity, specificity, positive predictive value, and negative predictive value of PET in detecting recurrent lung cancer were determined. RESULTS: FDG-PET correctly identified 14 out of 15 relapses and gave true negative results in six out of seven remissions, i.e., one false-negative and one false-positive were observed. The sensitivity, specificity, positive predictive value, and negative predictive value were 93%, 86%, 93%, and 86%, respectively. CONCLUSION: In 64% of the patients with unexplained increased CEA levels, FDG-PET provided decisive diagnostic clues guiding further diagnostic and therapeutic interventions. The selected use of FDG-PET for patients with re-elevated serum CEA levels after surgery can be a practical and effective mode of surveillance for detecting recurrent lung cancer.

[Human adjuvant disease which developed after silicone augumentation mammoplasty].

A 73-year-old woman was admitted to our hospital to evaluate mediastinal lymphadenopathy found on a chest CT scan. She had undergone mammoplasty with silicone augmentation 50 years previously and had the implants removed 5 years previously. Biopsied specimens of a mediastinal lymph node under video-assisted thoracic surgery (VATS) revealed multiple hyalinized non-caseating epithelioid cell granulomas and multinucleated giant cells and foamy macrophages containing some vacuoles. According to these clinicopathological findings, we diagnosed human adjuvant disease which developed after mammoplasty with silicone augmentation. In cases of mammoplasty, we should pay attention to the complication of chronic thoracic disorder as a human adjuvant disease.

[An autopsied case of mucinous bronchioloalveolar carcinoma associated with multiple thin-walled cavities].

A 82-year-old man was found to have mucinous bronchioloalveolar carcinoma associated with a cavity 10-cm in size in the right lower lobe, and he underwent a surgical lobectomy in April 2005 (pT2N0M0). Seven months after the surgery, chest images showed multiple metastases with thick-walled cavities in bilateral lung fields. The serial HRCT showed that thick-walled cavity lesions transformed into thin-walled cystic cavities associated with decreasing serum CEA levels. The patient's condition was good with best supportive care for 24 months from the time of recurrence. Subsequent progression of the thick-walled cavities into thin-walled cavities, was acompanied by re-elevation of serum CEA levels, and he died of respiratory failure 5 months after re-exacerbation. Macroscopic findings at autopsy showed multiple cavities in both lungs. Microscopic findings of the right lung showed desquamative mucinous bronchioloalveolar carcinoma cells lining the thick-walled cavity surface, and a single layer of tumor cells proliferating in the thin-walled cavity surface. Tumor cells with excessive mucus and necrosis were observed in the thick-walled cavities. It is suggested that thick-walled cavities were formed as a result of avascular necrosis and destruction of the pulmonary alveoli by excessive mucus, and thin-walled cavities were formed as a result of a check-valve mechanism.

[What is the role of pleuropneumonectomy in malignant pleural mesothelioma?].

In this report, the results of conventional pleuropneumonectomy in malignant diffuse mesothelioma are reviewed, and the role of this aggressive surgery in multidisciplinary treatment is discussed. The surgical results may improve owing to recent advances in medical technology, although the postoperative survival time after pleuropneumonectomy has remained nearly the same for the past 40 years. The problems with pleuropneumonectomy are high mortality and morbidity rates, high local recurrence rates, and almost the same survival rates as seen after pleurectomy. The indications for this aggressive surgery are limited to stage I, II, and III disease based on an accurate staging system, with induction therapy for macroscopic radical resection and postoperative chemoradiation therapy. In addition, patients must be monitored for the development of major complications perioperatively. The natural history of this disease should be clarified to determine the effectiveness of various forms of therapy. Precise analysis of the accumulated data from many institutions will help to improve the results of pleuropneumonectomy.

[Usefulness of FDG-PET for the diagnosis of postoperative recurrence of lung cancer].

No standardized postoperative follow-up strategy has been established for lung cancer patients, although CT and tumor markers are often employed. We conducted a retrospective study evaluating fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of postoperative recurrence of lung cancer. We evaluated 28 patients with suspected postoperative recurrence of lung cancer, who underwent FDG-PET between July 2004 and November 2005. Of these, 15 showed positive PET finings. Recurrence of lung cancer cases confirmed in 14 of these and the remaining case showed a postoperative scar. Thirteen patients with no findings on PET scan have demonstrated no evidence of recurrence during follow-up periods between 10 to 23 months. The negative predictive value was therefore 100%. FDG-PET in addition to chest CT and tumor markers for the diagnosis of the postoperative recurrence of lung cancer is considered to be beneficial in terms of avoiding excessive radiation exposure and limiting medical costs, but further evaluation in more patients is necessary.

[An autopsy case of obliterative bronchiolitis associated with Stevens-Johnson syndrome].

We reviewed an autopsied 27-year-old female with obliterative bronchiolitis associated with Stevens-Johnson syndrome. She had a history of Stevens-Johnson syndrome at age 10 years old and was treated with corticosteroids. Two months after the onset of dermatitis, the patient complained of dyspnea on exertion. The chest radiograph showed hyperinflation, and pulmonary function tests revealed obstructive impairment. The respiratory failure progressed due to respiratory tract infection and pneumothorax. She underwent thoracoscopic cyst surgery for right pneumothorax. Although the patient was clinically diagnosed as having obliterative bronchiolitis and received corticosteroids therapy and mechanical ventilation, she died of progressive respiratory failure 17 years after the onset of Stevens-Johnson syndrome. On autopsy, the macroscopic appearance of both lungs showed multiple white nodules in the centrilobular lesion corresponding to the obliteration of the small bronchioli. The microscopic appearance revealed constrictive bronchiolitis in the membranous bronchioli of both lungs associated with secondary bronchiectasis caused by superimposed infection.

[A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions].

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.

Occult cancer detected by positron emission tomography/computed tomography image fusion.

A 60-year-old male in a high-risk group for lung cancer, who also had positive sputum cytology, underwent examination by chest plain radiography, chest computed tomography (CT) and bronchofiberscopy. However, initially no abnormal findings were detected with these diagnostic modalities. Furthermore, thin-section spiral chest CT disclosed only a slight thickness of the right side of the tracheal wall, while consequent re-examination by bronchofiberscopy revealed only a light ulcerative lesion in the same area. However, the existence of a primary tumor was not confirmed using these modalities. Therefore, FDG-PET (positron emission tomography with fluorodeoxyglucose) was performed and demonstrated accumulation corresponding to the anterior mediastinum, although the exact location of the tumor was unclear by FDG-PET alone. Therefore, FDG-PET/CT image fusion was performed and resulted in the detection of a tracheal carcinoma on the outside of the right side of the tracheal wall. The patient then underwent tracheal sleeve resection including the tumor and tracheoplasty accompanied with wrapping using the flap of the thymus right lobe. To the best of our knowledge, this is the first reported case of tracheal carcinoma detected by FDG-PET/CT image fusion with consequent radical resection.

Tracheal release and thymus wrapping of the tracheoplasty anastomosis through mini-sternotomy.

Despite breakthroughs in general thoracic surgery, tracheoplasty remains a technically difficult procedure. The authors performed tracheoplasty on a 75-year-old woman diagnosed with recurrent thyroid cancer and tracheal invasion. Through an L-shaped unilateral mini-sternotomy added to a collar incision, we performed tracheal mobilization and release followed by resection of six tracheal rings. The tracheoplasty anastomosis was then wrapped with the right lobe of the thymus. Using this procedure, tracheoplasty was successfully performed with no complications related to the tracheal anastomosis. Tracheoplasty performed through mini-sternotomy, with a combination of full tracheal release and wrapping with the right lobe of the thymus, may represent a novel, effective, and less-invasive surgical procedure.

[A case of lung cancer with cyst formation].

A 70-year-old man was admitted with a nodule adjacent to a cystic lesion in the right lower lung field. Diagnosis of lung cancer was made by transbronchial biopsy. A series of chest radiographs revealed that a cystic lesion had presented 8 years before, and that a nodule appeared on the hilar side of the cyst 5 years later. The cyst may have been formed by the check-valve mechanism due to the lung cancer.

Placement of self-expandable metallic stents for tracheal stenosis secondary to thyroid cancer.

The indications and suitable approaches for treating upper airway obstruction secondary to thyroid cancer are controversial. Patients with thyroid cancer generally have a good prognosis, but airway stenosis and vocal cord paralysis are not uncommon. Subglottic airway stenting may be challenging, due to stent migration, granulation tissue formation and supraglottic stenosis. In this study, we evaluated the application of covered self-expandable metallic stents to relieve upper airway obstruction. This was a retrospective study of 5 patients with airway stenosis due to thyroid cancer treated in 2009 and 2010. Immediate airway enlargement was achieved in 3 patients with stenosis at the middle mediastinum. Gradual enlargement over 2 months was observed in the remaining 2 patients with stenosis at the cervical level. The performance status was improved in all 5 patients, including a case with anaplastic carcinoma. The follow-up averaged 13 months (range, 8-27 months). Granulation tissue developed at both ends of the stent in 3 patients, sputum was retained in 2 cases and bacterial colonization was detected in all 5 cases. No stent migration was reported. Additional tracheostomy was required in 2 patients, due to proximal tumor growth or progressive bilateral vocal cord paralysis after 10 and 6 months, respectively. In conclusion, stenting for central airway stenosis secondary to thyroid cancer may be beneficial, even in patients with anaplastic carcinoma. Long-term regular bronchoscopic follow-up is required to monitor complications, as patients with thyroid cancer are at high risk of granulation tissue formation, sputum retention and bacterial colonization.

Haemothorax following bullectomy caused by a sharp edge of the Endoloop.

A 22-year old man presented with a massive haemothorax 25 days after bullectomy for a spontaneous pneumothorax. Thoracoscopic surgery revealed ongoing bleeding from the chest wall caused by a sharp edge of the Endoloop Ligature (Ethicon Endo-Surgery) used to resect the remaining small part of the lung at the earlier staple bullectomy. The point where bleeding was occurring was clipped and covered using a collagen patch coated with human fibrinogen and thrombin. The protruding sharp edge of the Endoloop was excised together with the surrounding lung tissue, using a stapler. Although prevention of this type of complication is difficult, awareness of the potential problem may help in managing such extremely rare events.