A prospective observational study of postoperative adjuvant chemotherapy for non-small cell lung cancer in elderly patients (≥ 75 years).

BACKGROUND: To examine the effects of postoperative adjuvant chemotherapy for elderly (≥ 75 years of age) patients with completely resected non-small cell lung cancer (NSCLC), we conducted a multi-institutional and prospective observational study. METHODS: Patients were recruited between January 2014 and December 2017, and assigned to two cohort groups based on the patients' choice either to receive postoperative adjuvant chemotherapy (Cohort B) or not (Cohort A). All the patients were observed for 2 years after enrollment. The primary endpoint was the postoperative change of Karnofsky Performance Status (KPS) at 2 years. The secondary endpoints were postoperative recurrence-free survival (RFS) and overall survival (OS) at 2 years, and the completion rate of the adjuvant chemotherapy. RESULTS: Two hundred and seventy-two patients were enrolled (Cohort A, n = 225; Cohort B, n = 47). At any time point after surgery, no marked difference of KPS was observed between Cohort B and Cohort A. The RFS at 2 years was 70.8% (95% confidence interval [CI], 64.3-76.4) in Cohort A and 76.0% (95% CI 60.8-85.9) in Cohort B. The OS at 2 years was 85.9% (95% CI 80.4-89.9) in Cohort A and 89.1% (95% CI 75.8-95.3) in Cohort B. The completion rate of planned chemotherapy was 49.9% (95% CI 34.1-63.9%). CONCLUSIONS: The elderly patients were not likely to choose to receive postoperative adjuvant chemotherapy; however, no significant adverse effect on postoperative KPS was identified. TRIAL REGISTRATION: Clinical Trial Registration ID: UMIN000020736.

Successful curative surgery for postoperative oesophageal recurrence of oesophagogastric junction cancer.

A man in his 70s had undergone total gastrectomy for oesophagogastric junction cancer. Three years and 11 months later, he began to vomit after meals and was diagnosed with mediastinal recurrence of oesophagogastric junction cancer. A CT scan showed that the tumour was suspected of infiltrating the aorta and lung. He received two cycles of chemotherapy with S-1 plus cisplatin, resulting in tumour reduction. The patient underwent resection of the lower oesophagus, including the tumour, the left lower lobe of the lung and the pericardium through a left thoracoabdominal incision. This is the first report of a patient surgically resected for postoperative oesophageal recurrence of oesophagogastric junction cancer. Although most postoperative recurrences of oesophagogastric junction cancer are far advanced at the time of diagnosis and prognosis is poor, chemotherapy followed by surgery may improve the prognosis of patients with locoregional recurrence.

The influence of comorbidity on the postoperative survival in elderly (≥ 75 years old) with lung cancer.

OBJECTIVES: We conducted a multi-institutional prospective observational study of elderly patients (≥ 75 years-old) with resected non-small cell lung cancer. In this report, we have followed the cohorts for 2 years after surgery and examined both the influence of preoperative comorbidity [Adult Comorbidity Evaluation-27 (ACE-27) index] on the postoperative survival and the change in the Karnofsky Performance Status (KPS). METHODS: From March 2014 to April 2015, 264 patients were prospectively registered from 22 hospitals affiliated with the National Hospital Organization. The mean age at the time of surgery was 79.3 years (range 75-90 years), and 41% of the patients were ≥ 80 years of age. A total of 26% underwent sublobar resection. The study endpoints were the postoperative overall survival (OS), its prognostic factors, and the changes in the postoperative KPS. RESULTS: The 2-year OS was 85.3% (95% confidence interval 80.4-89.1%). Male gender, age ≥ 80, a smoking history, grade 2 of ACE-27, and an advanced disease stage were significantly poor prognostic factors for the OS in the univariate risk analysis. The multivariate analysis showed that male gender, age ≥ 80, an advanced disease stage and sublobar resection were significantly poor prognostic factors for the OS. In comparison with the preoperative KPS, no marked decline was observed in the postoperative chorological change of KPS. CONCLUSIONS: In the surgical treatment of elderly patients, the comorbidity as assessed by the ACE-27 index might affect the postoperative survival, and therefore should be taken into accounts in the preoperative evaluation of the surgical indications.

A randomized phase II study to assess the effect of adjuvant immunotherapy using α-GalCer-pulsed dendritic cells in the patients with completely resected stage II-IIIA non-small cell lung cancer: study protocol for a randomized controlled trial.

BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). METHODS: Subsequent to the complete resection of NSCLC, followed by the administration of cisplatin plus vinorelbine dual-agent combination adjuvant chemotherapy, patients who satisfy the inclusion criteria will be randomly allocated to either the α-GalCer-pulsed DC immune therapy group, or the standard treatment group. In total, 56 patients will be included in the study. The primary endpoint is recurrence-free survival, and the secondary endpoints are natural killer T-cell-specific immune response, the frequency of toxic effects and safety, and overall survival. DISCUSSION: In order to determine the efficacy of α-GalCer-pulsed DC therapy, the present study compares patients with stage II-III NSCLC who underwent complete surgical resection followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to those who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). TRIAL REGISTRATION: UMIN000010386 ( R000012145 ). Registered on 1 April 2013. UMIN-CTR is officially recognized as a registration site which satisfies ICMJE criteria.

Comparison of the prognostic values of preoperative inflammation-based parameters in patients with breast cancer.

Peripheral blood-derived inflammation-based markers, including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are indicators of prognosis in various malignant tumors. The present study aimed to identify the inflammation-based parameters that are most suitable for predicting outcomes in patients with breast cancer. Two hundred ninety-six patients who underwent surgery for localized breast cancer were reviewed retrospectively. The association between clinicopathological factors and inflammation-based parameters were investigated. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic indicators associated with disease-free survival (DFS). The NLR level correlated significantly with tumor size (P<0.05). The PLR level correlated with the expression of estrogen receptor and lymph node involvement (P<0.05). Univariate analysis revealed that lower CRP and PLR values as well as tumor size, lymph node involvement, and nuclear grade were significantly associated with superior DFS (CRP: P<0.01; PLR, tumor size, lymph node involvement, and nuclear grade: P<0.05). On multivariate analysis, CRP (hazard ratio [HR]: 2.85, 95% confidence interval [CI]: 1.03-7.88, P<0.05), PLR (HR: 2.61, 95% CI: 1.07-6.36, P<0.05) and nuclear grade (HR: 3.066, 95% CI: 1.26-7.49, P<0.05) were significant prognostic indicators of DFS in patients with breast cancer. Neither LMR nor NLR significantly predicted DFS. Both preoperative CRP and PLR values were independently associated with poor prognosis in patients with breast carcinoma; these were superior to other inflammation-based scores in terms of prognostic ability.

A Prospective Observational Study of Pulmonary Resection for Non-small Cell Lung Cancer in Patients Older Than 75 Years.

The operative morbidity rate in elderly patients with lung cancer is high in comparison to nonelderly patients, probably because of the increase in comorbidities that occurs with aging. However, previous reports were retrospective and were performed at single institutions; thus, the preoperative comorbidities and operative morbidity could not be fully assessed. We conducted a multi-institutional prospective observational study of elderly patients (>75 years of age) with a completely resected non-small cell lung cancer. From March 2014 to April 2015, 264 patients from 22 hospitals affiliated with the National Hospital Organization in Japan were prospectively registered in the present study. The primary end point was operative morbidity (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0). The secondary end points were operative mortality and the risk factors for operative morbidity. Preoperative comorbidities were assessed according to the Adult Comorbidity Evaluation-27 index. The mean age at the time of surgery was 79.3 years (range 75-90 years). Forty-one percent of the patients were >80 years of age. Twenty-six percent underwent sublobar resection. The incidence of morbidities of any grade was 43.2% (90% confidence interval: 38.2%-48.2%). Respiratory system-related morbidity (19.3%), followed by cardiovascular system-related morbidity (10.2%), was the most common morbidity. The in-hospital mortality rate was 1.1% (3 of 264 patients). A multivariate analysis of the risk factors for operative morbidity showed that both Adult Comorbidity Evaluation-27 grade and the blood loss volume were significant factors. The results of the present prospective multi-institutional study should be used as a reference in the surgical treatment of elderly patients with lung cancer.

Prognostic Factors for Survival after Resection of Pulmonary Metastases from Colorectal Carcinoma.

PURPOSE: As chemotherapy has improved, the survival of patients with metastatic colorectal carcinoma has reached up to 2.5 years. Many of these patients experience pulmonary metastases; however, the prognosis after pulmonary metastasectomy is not satisfying. In this study, we analyzed the prognostic factors for survival in patients who underwent pulmonary metastasectomy. METHODS: Eighty-seven patients with colorectal carcinoma received pulmonary metastasectomy. The pathological status of the primary tumor, outcome of the pulmonary metastasectomy, disease-free interval, perioperative carcinoembryonic antigen (CEA) level and history of liver metastases were assessed. RESULTS: The five-year survival was 42.5% after pulmonary metastasectomy. A univariate analyses revealed that the CEA level (p = 0.043) and the number of pulmonary metastases (p = 0.047) were prognostic factors for survival. The CEA level was an independent prognostic factor in a multivariate analysis (relative risk = 2.01, p = 0.037). Among cases with elevated preoperative CEA levels, those whose CEA level normalized after metastasectomy had a better prognosis compared with those whose CEA level decreased but was still high, or whose level increased after metastasectomy (median survival time of 41.8 months compared with 28.1 or 15.7 months, respectively p = 0.021). CONCLUSION: The CEA level can be a predictive marker for the prognosis in patients with pulmonary metastases from colorectal carcinoma.

Carcinoma of the ampulla of Vater diagnosed after surgical treatment for Lemmel's syndrome.

Lemmel's syndrome encompasses a range of conditions in which a juxtapapillary duodenal diverticulum exerts mechanical and functional effects on the common bile and pancreatic ducts, leading to jaundice and pancreatitis. In this report, we describe a very rare case of carcinoma of the ampulla of Vater that was detected during postoperative follow-up in a patient who had undergone choledochojejunostomy following a diagnosis of Lemmel's syndrome. We present our clinical and pathological experiences with the diagnosis and treatment of this case as well as a review of the present literature concerning Lemmel's syndrome.

Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer.

Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer (NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient's life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence (distant, locoregional or combined) and the treatment modality: (1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage IV disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC; (2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice for oligometastatic recurrence; and (3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage IIIA and IIIB disease.

Local treatment of oligometastatic recurrence in patients with resected non-small cell lung cancer.

OBJECTIVES: We previously reported a retrospective study indicating the prognostic impact of the local treatment of oligometastatic recurrence after a complete resection for non-small cell lung cancer (NSCLC). In the present study, we prospectively observed postoperative oligometastatic patients and investigated the effects of local treatment on progression-free survival (PFS). METHODS: Using a prospectively maintained database of patients with completely resected NSCLC treated between October 2007 and December 2011, we identified 52 consecutive patients with postoperative recurrence, excluding second primary lung cancer. Of these patients, 31 suffering from distant metastases alone without primary site recurrence were included in this study. According to the definition of 'oligometastases' as a limited number of distant metastases ranging from one to three, 17 patients had oligometastatic disease. Of those 17 patients, four patients with only brain metastasis were excluded from the analysis. RESULTS: The oligometastatic sites included the lungs in five patients, bone in four patients, the lungs and brain in two patients, the adrenal glands in one patient and soft tissue in one patient. Eleven of the 13 patients first received local treatment. Three patients (lung, adrenal gland, soft tissue) underwent surgical resection, and the remaining eight patients received radiotherapy. The median PFS was 20 months in the oligometastatic patients who received local treatment. There were five patients with a PFS of longer than two years. The metastatic sites in these patients varied, and one patient had three lesions. On the other hand, the two remaining patients first received a systemic chemotherapy of their own selection. The PFS of these two patients was five and 15 months, respectively. CONCLUSION: Local therapy is a choice for first-line treatment in patients with postoperative oligometastatic recurrence.

[Chest surgery in patients with pulmonary metastasis from head and neck cancer].

There have been only a few reports about a surgical resection of pulmonary metastasis from malignant head and neck tumors. Here we reviewed the literatures concerning the surgical results of pulmonary metastasectomy from malignant head and neck tumors, and discussed the indication for surgery. The 5-year overall survival after a metastasectomy was approximately 50.0% including all the histological types of head and neck cancer. Limiting to the squamous cell carcinoma (SCC), the 5-year overall survival was approximately 30.0%. Of the head and neck SCCs, the oral cavity SCC such as SCC of the tongue showed an extremely poor survival after metastasectomy. A pulmonary metastasectomy of squamous cell carcinoma is thus justified with the exception of oral cavity origin. Both adenoid cystic carcinoma of salivary glands and thyroid cancer are of low malignant nature, and the progression after occurrence of distant metastases is also very slow. Therefore, the survival benefit by those pulmonary metastasectomy is not evident.

Prognosis and therapeutic response according to the World Health Organization histological classification in advanced thymoma.

PURPOSE: The clinical efficacy of the World Health Organization (WHO) classification of thymoma has been reported to be a prognostic factor for patients with thymomas. This study focuses on the relationship between the therapeutic response and the WHO histological classification in patients with advanced thymoma. METHODS: A retrospective review was performed on 22 patients with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1, 7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3, respectively. RESULTS: Surgery was performed on 10 patients. There were 2 complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of 18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy, chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The response rate in 9 patients with type A-B2 was significantly better than that in 9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P = 0.0001). Only the WHO classification was significantly associated with survival, with type B3 having a worse prognosis than A-B2 (P = 0.01). CONCLUSIONS: Type B3 thymoma showed a lower response rate to treatments and thus shorter survival. The WHO classification is a good predictive factor for therapeutic response in advanced thymoma.

Prognostic factors in non-small cell lung cancer patients with postoperative recurrence following third-generation chemotherapy.

AIM: To analyse the prognostic factors for patients with non-small cell lung cancer (NSCLC) who underwent cytotoxic chemotherapy with third generation agents or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrence. PATIENTS AND METHODS: Between 1997 and 2005, 479 patients underwent a complete resection for NSCLC. Of these, 112 patients underwent chemotherapy for postoperative recurrence. RESULTS: Median postrecurrence survival time for these 112 patients was 25.6 months. Univariate analysis showed female gender, age younger than 65 years, ECOG performance status of 0-1, never-smoker status, and adenocarcinoma prolonged survival, whereas metastasis to the liver or adrenal gland shortened survival. Multivariate analysis revealed age, performance status, cell type and metastasis to the adrenal gland to be independent prognostic factors. CONCLUSION: Age, performance status, cell type, and metastasis to the adrenal were independent prognostic factors in NSCLC patients treated with third-generation agents or EGFR-TKI for recurrence.

Non-small cell lung carcinoma of the superior sulcus: The evolution of treatment outcomes with multimodality treatment at a single institution.

OBJECTIVES: We evaluated the efficacy of the multimodality approach in treating superior sulcus non-small cell lung carcinoma (SS NSCLC). METHODS: We retrospectively analyzed the records of 57 patients with SS NSCLC who were treated at our institution between 1982 and 2007. RESULTS: During the study period, 3- and 5-year survival increased significantly from 42.6% and 42.6% in the first half of the study period (1982-1994) to 72.7% and 65.4% in the second half (1995-2007), respectively. Methods of clinical staging were unchanged between the two time periods, although the ratio of adenocarcinoma was increased, and multimodality treatment, particularly concurrent chemoradiotherapy followed by surgical resection, was used more frequently in the second half of the study period. The 5-year survival of patients who received preoperative chemoradiotherapy followed by surgery (n = 27) was better than that of those who received other treatment regimen with surgery (n = 22, 64.6% vs. 49.6%; P = 0.044). Five-year survival in patients with complete resection after chemoradiotherapy was 70.4%. Thirteen patients (48%) achieved a pathologic complete response or minimal microscopic disease. CONCLUSIONS: Multimodality treatment with concurrent chemoradiotherapy followed by surgery appears to contribute to improved outcomes over time in patients with SS NSCLC.

Prognostic factors in previously treated non-small cell lung cancer patients with and without a positive response to the subsequent treatment with gefitinib.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been reported to have a certain anti-tumor effect in previously treated patients with non-small cell lung cancer (NSCLC). However, the prognostic factors in those patients with and without a positive response to gefitinib treatment remain unclear. A retrospective chart review was performed in 131 advanced NSCLC patients who received 250 mg of gefitinib as either a second-line or even later stage treatment from July 2002 to December 2005. The clinical factors including age, gender, performance status (PS), stage, histology, the number of prior types of chemotherapy, and the response to first-line chemotherapy were analyzed. One and 38 patients experienced a complete and partial response, respectively, to gefitinib treatment with an overall response rate of 30%. The median survival time (MST) of all patients receiving gefitinib treatment was 10 months while the MST was 28 months in the 39 gefitinib responders and 6 months in the 92 non-responders. Among the 39 gefitinib responders, the predominant prognostic factor was found to be the effectiveness of the first-line chemotherapy. The MST of the 20 patients with a response to the first-line chemotherapy was 32 months while the MST of the 19 patients without a response to the chemotherapy was 22 months (p=0.025). Among the 92 gefitinib non-responders, the predominant prognostic factor was the PS (p<0.001). The effectiveness of the first-line chemotherapy was therefore found to be a prognostic factor in the gefitinib responders with previously treated NSCLC, while the PS was shown to be a prognostic factor in the gefitinib non-responders.

Resection of mediastinal granulocytic sarcoma triggered the rapid progression of acute myeloid leukemia.

Mediastinal granulocytic sarcoma (GS) is a relatively rare disease. We experienced a case of acute myeloid leukemia (AML) that took a rapid turn for the worse after the resection of a mediastinal GS. A healthy 60-year-old man had been in good general health all his life, but was diagnosed with a mediastinal tumor by his family physician and was referred to our department. The patient underwent resection of the mediastinal tumor because thymoma was highly suspected. On postoperative day (POD) 3, the patient suffered a fever as well as an elevated white blood cell (WBC) count and a high C-reactive protein level. His WBC count was 77,240 at its peak on POD 9, at which point the patient was diagnosed with AML by bone marrow aspiration. The immunohistological findings showed the features of leukemia, and GS was diagnosed. Despite chemotherapy, the patient died on POD 28 as a result of rapid disease progression.

Late-period-onset chylothorax after a pulmonary resection for lung cancer: a case report.

A 65-year-old female had been diagnosed with right lung cancer by her family physician, and she was introduced to our Department of Thoracic Surgery at Matsuyama Red Cross Hospital in May 2004. She underwent a right upper lobectomy and wedge resection of S6 with the systematic dissection of her mediastinal lymph nodes. The patient made an uneventful recovery and was discharged on postoperative day 19. However, chylothorax was detected on a chest roentgenogram when she consulted our outpatient clinic again for dyspnea on exertion and chest pain. Chylothorax occurred in postoperative day 34. The patient initially received conservative therapy, but subsequently underwent surgical treatment and fibrin glue intubation when conservative therapy proved to be unsuccessful.

Completely wide resection of malignant fibrous histiocytoma of the chest wall; expect for long survival.

Malignant fibrous histiocytoma (MFH) rarely occurs in the chest wall. A case of MFH originating from the chest wall is herein reported. We performed radical en-block resection of the whole chest wall together with the tumor and reconstructed it with Marlex mesh. There was no recurrence 4 years after operation. We consider radical en-block resection for MFH and reconstruction with Marlex mesh a safe operation and may provide a long-term survival.

Intrapleural hypotonic cisplatin treatment for malignant pleural mesothelioma: in vitro experiments and clinical application.

PURPOSE: We studied the inhibitory effects of hypotonic cisplatin on the growth of malignant pleural mesothelioma (MPM) cell lines in vitro, and assessed the effectiveness of intraoperative intrapleural hypotonic cisplatin treatment combined with extrapleural pneumonectomy for patients with this tumor. METHODS: In the in vitro experiments, mesothelioma cell lines were exposed to various concentrations of cisplatin in either saline solution or distilled water for up to 5 min. After 48 h incubation, we calculated the inhibition of cell growth. In the clinical study, five patients with MPM underwent intraoperative intrapleural hypotonic cisplatin treatment combined with extrapleural pneumonectomy. RESULTS: The hypotonic cisplatin treatment inhibited cell growth at a significantly greater rate than the isotonic cisplatin treatment. Just 1-5 min exposure to 10 microg/ml of hypotonic cisplatin inhibited growth by more than 80%. Clinically, no recurrence was found in four of the five patients after a median follow-up period of 27 months (range: 16-36 months), although contralateral multiple pulmonary metastases were found in one patient 10 months after surgery. CONCLUSION: Hypotonic cisplatin treatment is effective against MPM, and should be investigated further.

Video-assisted thoracoscopic resection of a giant anterior mediastinal tumor (lipoma) using an original sternum-lifting technique.

We report here the complete thoracoscopic resection of a giant lipoma (18x15x5 cm, 560 g) in a 33-year-old man using an original sternum-lifting technique. The patient had an uncomplicated postoperative course and was discharged on the seventh postoperative day. This is the largest reported anterior mediastinal tumor that was completely resected by video-assisted thoracic surgery without median sternotomy or thoracotomy. This original method may be useful from the standpoint of minimal access, rapid recovery, less pain, and good cosmetic results for an anterior mediastinal giant tumor.