Efficacy of Neoadjuvant Chemotherapy in Distal Pancreatectomy with En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer.

BACKGROUNDS: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an extended surgical procedure for patients with locally advanced cancer of the pancreatic body and tail. Recently, the usability of neoadjuvant chemotherapy (NAC) in pancreatic cancer was reported. The purpose of this study was to clarify the impact of NAC on surgical outcomes and prognosis in DP-CAR patients. METHODS: This study retrospectively reviewed 20 consecutive patients who underwent DP-CAR at a single institution. RESULTS: Eleven of 20 patients (55.0%) received NAC. Their first regimens were gemcitabine (GEM) plus nab-PTX (n = 7, 63.6%), GEM plus S-1 (n = 3, 27.3%), and GEM (n = 1, 9.1%). Although two patients converted to a second regimen, none abandoned NAC due to adverse effects or could not undergo a planned procedure for disease progression. There were no significant differences in intraoperative variables, morbidity, including pancreatic fistula and delayed gastric emptying, and mortality between patients with and without NAC; however, patients with NAC had a significantly lower proportion of arterial invasion (p = 0.025), lymphatic invasion (p < 0.0001), and vascular invasion (p = 0.035). There were no significant differences in the induction rate of adjuvant chemotherapy (p = 0.201). The recurrence-free survival and overall survival rates in patients with NAC were significantly higher than in patients without NAC (p = 0.041 and p = 0.018, respectively). CONCLUSION: DP-CAR following NAC was associated with a preferable prognosis and had no negative effect on surgical outcomes. Therefore, NAC in DP-CAR patients might be a beneficial and safe therapeutic strategy.

A phase II randomized trial of adjuvant chemotherapy with S-1 versus S-1 plus cisplatin for completely resected pathological stage II/IIIA non-small cell lung cancer.

OBJECTIVES: Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC. PATIENTS AND METHODS: We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7th TNM classification) who underwent complete resection from 2009 to 2013. The primary endpoint, the 2-year disease-free survival (DFS) rate, was evaluated using the Bayesian method. Eligible patients were randomly assigned to two arms: oral S-1 monotherapy (S-1 arm) and S-1 plus cisplatin combination therapy followed by S-1 (S-1 plus cisplatin arm) both for a total of 1 year. RESULTS: A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P = 0.1695 and P = 0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%). CONCLUSIONS: Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.

Laparoscopic Left Hepatectomy for Ruptured Hepatocellular Carcinoma Controlled After Transcatheter Arterial Embolization: Case Report and Review of the Literature.

BACKGROUND: Although spontaneous tumour rupture is a life-threatening complication of hepatocellular carcinoma (HCC), staged hepatectomy for HCC controlled after transcatheter arterial embolization (TAE) could provide a better prognosis. Laparoscopic liver resection (LLR) has been accepted worldwide and has been expanded from minor resection to anatomical major resection. We herein report the first case of pure laparoscopic left hepatectomy for ruptured HCC controlled after TAE. CASE REPORT: A 66-year-old man was transferred to our Institute because of abdominal pain and decreased consciousness. Ruptured HCC in segment IV and massive intra-abdominal haemorrhage were diagnosed. Emergency TAE was performed, achieving haemostasis. Reduction of intra-abdominal haemorrhage was confirmed at the 3-month follow-up, and no intrahepatic metastasis or peritoneal dissemination was present. Therefore, we performed elective laparoscopic left hepatectomy for the remaining HCC 110 days after TAE. Although dense adhesion was found in the upper right peritoneal cavity and greater omentum enveloping the remaining haemorrhage on the underside of the liver, there was no disseminated involvement in the peritoneal cavity. The operative time was 194 minutes, and intraoperative blood loss was 100 g. The postoperative course was uneventful, and the patient was discharged on postoperative day 6. CONCLUSION: Major LLR may be an option for staged hepatectomy in patients with ruptured HCC controlled after TAE.

Pulmonary Resection for a Residual Tumor after Definitive Radiation in Locally Advanced Non-Small Cell Lung Cancer.

OBJECTIVE AND METHODS: To clarify the benefits of surgery for a persistent tumor following definitive radiation in locally advanced non-small cell lung cancer, five patients were retrospectively reviewed. RESULTS: All patients received definitive radiation, and three received concurrent chemotherapy followed by anatomical lung resection for a residual local tumor. The median time from the radiation to surgery was 8.2 weeks. There were no postoperative mortalities. Four patients developed distant metastasis with a mean recurrence-free interval of 7.5 months. CONCLUSIONS: Distant metastasis frequently occurred within a relatively short period after surgery. Further studies with a larger sample size are needed.

Surgical Outcomes of Non-small Cell Lung Cancer in Patients with a History of Pancreaticobiliary Cancer.

AIM: To determine the efficacy of surgery for non-small cell lung cancer in patients who had previously undergone surgery for pancreaticobiliary cancer. PATIENTS AND METHODS: Seven patients who underwent pulmonary resection for primary lung cancer after curative surgery for pancreaticobiliary cancer at our Institution from 2006 to 2016 were retrospectively evaluated. RESULTS: Five patients had metachronous and two patients had synchronous cancer of pancreaticobiliary and lung origin. The median time between surgeries for the two cancers was 35 months. All patients underwent complete resection of both cancers. The 5-year survival was 68.6% after pulmonary resection. Two patients had recurrence after lung surgery, with a mean recurrence-free interval of 6.5 months. CONCLUSION: Surgery should be considered for lung cancer in patients who have undergone curative surgery for pancreaticobiliary cancer.

Surgical Resection for Pulmonary Metastasis from Pancreatic and Biliary Tract Cancer.

AIM: To determine the efficacy of pulmonary metastasectomy for pancreatic and biliary tract cancer. PATIENTS AND METHODS: Ten patients who underwent therapeutic pulmonary metastasectomy after resection for pancreatic and biliary tract cancer at our Institution from 2006 to 2016 were retrospectively evaluated. RESULTS: The primary site was the pancreas in four patients and biliary tract in six. Nine patients had single metastasis, and one patient had bilateral multiple metastases. The median time from surgery for the primary tumor to pulmonary resection was 23.3 months (range= 0-47.1 months). One patient underwent lobectomy, while nine patients underwent partial resection. One patient had incomplete resection due to pleural dissemination. There were no postoperative mortalities or major morbidities. The mean follow-up period was 26.0 months. The median survival time was 38.5 months, and the estimated 5-year overall survival was 38.9% after pulmonary resection. Five patients had recurrent disease after pulmonary resection, with a median recurrence-free interval of 6.0 months. One patient underwent second pulmonary resection for a solitary lung recurrence. CONCLUSION: Despite the poor prognoses of these cancer types, pulmonary metastasectomy can significantly prolong survival in selected patients with pancreatic and biliary tract cancer.

Long-term surviving patient with inferior vena cava tumor thrombus and extrahepatic metastasis after spontaneous ruptured hepatocellular carcinoma.

We present a case of long-term survival in a patient with inferior vena cava tumor thrombus (IVCTT) and extrahepatic metastasis after resection for spontaneous ruptured hepatocellular carcinoma (HCC). The patient was a 73-year-old Japanese man previously diagnosed with chronic hepatitis B. He was referred to our emergency room and diagnosed with spontaneous ruptured HCC. The patient was immediately treated with transcatheter arterial embolization, and we then performed second-stage hepatic resection 50 days later. Although des-gamma-carboxy prothrombin was reduced to a normal level after hepatectomy, it gradually increased and computed tomography showed a disseminated tumor in the diaphragm near S2 of the liver with IVCTT and right atrium tumor thrombus. Recurrent HCC was treated with monthly transcatheter arterial infusion chemotherapy (TAI) and conformal radiotherapy (RT) of 40 Gy. After TAI and RT procedures, the disseminated tumor and IVCTT completely disappeared. Four years after TAI and RT procedures, the tumors were well controlled with no local recurrence. About 6-7 years after spontaneous ruptured HCC, lung metastasis and spleen metastasis were detected and resected, respectively. The patient is still alive and doing well over 7 years after spontaneous ruptured HCC.

Phase II study of uracil-tegafur plus cisplatin in patients with previously untreated advanced non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: A multi-institutional phase II trial combining uracil-tegafur (UFT) and cisplatin (CDDP) was conducted in patients with previously untreated advanced non-small cell lung cancer (NSCLC) to evaluate the safety and efficacy of this combined treatment regimen. METHODS: The entry criteria for this study were previously untreated NSCLC, measurable disease, age <80 years, performance status <2, and adequate haematological, hepatic and renal function. Patients were treated with 400 mg/m(2) oral UFT from day 1 to day 14 and 80 mg/m(2) cisplatin on day 15. The treatment course was repeated every 3 weeks. RESULTS: Of the 68 patients enrolled, 64 (27 with stage IIIB and 37 with stage IV disease) were eligible for treatment. Twenty of the 64 patients responded to the chemotherapy (response rate 31.3%; 95% CI 21.2-43.4%). The median survival time was 8.6 months, and the 1-year survival was 41.5%. Haematological toxicity >or=WHO grade 3 was seen in 3 (4.7%) patients. For non-haematological toxicities, anorexia with WHO grade 3 was seen in 8 (12.5%) patients, nausea and vomiting with WHO grade 3 in 4 (6.3%), diarrhoea with WHO grade 4 in 1 (1.6%), and liver dysfunction with WHO grade 4 in 1 (1.6%) patient. CONCLUSIONS: The combination of oral UFT plus cisplatin was found to be a safe and active treatment against advanced NSCLC. The observed low toxicity of this combined regimen may warrant its application to the treatment of elderly patients.

Clinical characterization of node-negative lung adenocarcinoma: results of a prospective investigation.

OBJECTIVES: In clinical stage IA lung adenocarcinoma, the clinical features of a truly node-negative population were prospectively investigated by means of a prospective investigational study. METHODS: The clinical data and radiographic features of high-resolution computed tomography (HR-CT) were registered before operation in 169 clinical stage IA lung cancer patients who were scheduled to undergo a standard lobectomy and systemic mediastinal node dissection. The nodal metastasis was pathologically defined and the clinical factors associated with the presence of the nodal metastasis were evaluated. RESULTS: In 114 assessable cases with adenocarcinomas, 15 (13.1%) were node-positive. The serum carcinoembryonic antigen (CEA), retraction sign, and intratumoral air-bronchogram on HR-CT were suggested to be predictive factors for lymph node metastasis, with hazard ratios of 12.44 (p = 0.0003), 6.53 (p = 0.0533), and 0.17 (p = 0.0073), respectively. In combination with the radiologic features and serum CEA, cases with elevated serum CEA or presence of retraction sign included 15.6% of node metastasis-positive, whereas all cases with normal CEA and absence of retraction sign showed no nodal metastasis. Cases with elevated serum CEA or absence of intratumoral air-bronchogram included 24.5% of node metastasis, whereas cases with normal CEA and presence of air-bronchogram showed 4.6% of node metastasis. The tumor size and the proportion of ground-glass attenuation were not associated with the incidence of nodal metastasis. CONCLUSIONS: The serum CEA and HR-CT features thus allowed us to identify node-negative lung adenocarcinomas measuring 3 cm or less in size.

A small randomized phase III single-center trial on postoperative UFT administration in patients with completely resected non-small cell lung cancer.

Our objective was to clarify the efficacy of UFT administration after the complete resection of non-small cell lung cancer (NSCLC) at a single-center institution, avoiding the biases produced by interinstitutional differences. A total of 30 patients who underwent the complete resection of NSCLC at our hospital between 1987 and 2001 were randomly assigned to a control group or to a UFT group (400 mg/day for 2 years). Thirteen patients were assigned to the control group and 17 patients were assigned to the UFT group. The overall survival rate, disease-free survival rate, patient compliance and adverse effect of the UFT treatment were then analyzed. The overall survival and disease-free survival rates of the UFT group were superior to those of the control group. Four patients in the UFT group received medication for 24 months and 14 patients were treated for more than 3 months. No severe adverse effects were observed. Seven patients suffered a relapse in the control group. Two patients suffered a relapse in the UFT group, but the relapse occurred after the discontinuation of UFT administration. We conclude that the administration of UFT as an adjuvant therapy prolonged the overall survival and disease-free survival rates of patients after the resection of NSCLC in a small study performed at a single institution. Interinstitutional differences, particularly operating procedures, should be carefully considered when performing large multicenter clinical studies.

Prognosis of non-surgically treated, clinical stage I lung cancer patients in Japan.

OBJECTIVE: The optimal management of stage I lung cancer is surgical resection. However, some of these patients are not candidates for surgery because of several medical problems. We analyzed prognosis of non-surgically treated, clinical stage I lung cancer patients. METHODS AND RESULTS: There were 21211 lung cancer patients registered from 1982 to 1991 in the data-base of the Japanese National Chest Hospital Study Group for Lung Cancer, and the number of non-surgically treated, clinical stage I lung cancer patients during the 10 years was 802. The 5- and 10-year survival rates of the 799 patients, exclusive of two carcinoid tumors and one adenid cystic carcinoma which have good prognosis, were 16.6 and 7.4%. We analyzed the 799 patients according to several prognostic factors. Sex, T factor of the tumor, histology, performance status and the method in which lung cancer was detected were prognostic factors, but age and treatment method were not associated with prognosis. Forty-nine patients survived for 5 years or more without surgical resection, but the survival rate continued to decrease even after 5 years, and the 7- and 10- year survival rates were 34.4 and 18.1% in the 49 patients. CONCLUSIONS: It is a fact that there are long-term survivors in non-surgically treated, stage I lung cancer patients. However, the rate is low, and the survival curve continues to decrease even after 5 years. Long-term survivors might suggest the presence of a lung cancer in which the tumor growth is slow.

Subcarinal bronchogenic cyst with high carbohydrate antigen 19-9 production.

In a rare case of bronchogenic cyst with high carbohydrate antigen (CA) 19-9 production, a 57-year-old man with coughing and chest pain was diagnosed with a subcarinal mediastinal tumor. Fiberoptic bronchoscopy showed an erosive mucosal lesion overlying the area of extrinsic compression at the membranous of the right mainstem bronchus. Serum carbohydrate antigen 19-9 was elevated at 1300 U/ml. Thoracotomy showed an encapsulated cyst tightly adhering to the right main bronchus. The cyst was extirpated after ablation at the adherent cystic wall by electrocautery. Although intracystic carbohydrate antigen 19-9 concentration was very high, serum carbohydrate antigen 19-9 and bronchoscopic findings returned to normal postoperatively. The histological diagnosis was consistent with a bronchogenic cyst and carbohydrate antigen 19-9 could be immunohistochemically demonstrated within its epithelium.

Malignant minor pleural effusion detected on thoracotomy for patients with non-small cell lung cancer: is tumor resection beneficial for prognosis?

BACKGROUND: This study attempts to clarify the benefit of surgery for non-small cell lung cancer (NSCLC) with malignant minor pleural effusion that is detected at thoracotomy. METHODS: Records of surgical patients with NSCLC were reviewed, with a definition of minor pleural effusion as less than 300 mL. The patients were divided into three groups as follows: (1) group C consisted of patients who underwent grossly complete resection; group I, patients with incomplete tumor resection; and group E, patients who underwent exploratory thoracotomy only. RESULTS: There were 196 patients who had minor pleural effusion; of these, 96 (46%) underwent an examination to define the malignancy status of pleural effusion after surgery. In 43 patients (45%), the effusion was found to be malignant. The median survival time and 5-year survival rate, respectively, were 13 months and 9% for group C (n = 11); 34 months and 10% for group I (n = 14; p = 0.3); and 17 months and 0% for group E (n = 18; p = 0.8). CONCLUSIONS: Tumor resection is not beneficial for the survival of patients with NSCLC who have a minor malignant pleural effusion.

Chemotherapy for small cell lung cancer in patients over 80 years old.

BACKGROUND: Elderly cancer patients sometimes are not considered candidates for standard chemotherapy. We evaluated the efficacy of chemotherapy for small cell lung cancer (SCLC) in patients aged over 80 years old. PATIENTS AND METHODS: We retrospectively analyzed the records of 10 SCLC patients over 80 years old. Six of them had received carboplatin and etoposide intravenously, two had etoposide orally, and two had only supportive care. RESULTS: Seven of the 8 patients treated with chemotherapy responded partially and the median survival time was 281 days. Despite the toxicity of the chemotherapy, the performance status was improved in 5 out of 8 treated patients and the cancer-related symptom was relieved in all treated patients for at least one month during and/or after chemotherapy. CONCLUSION: Chemotherapy is indicated for SCLC patients even aged over 80 years. The quality of life is improved by chemotherapy, although the survival time may not be prolonged significantly.