A case of advanced mucinous cystadenocarcinoma of the pancreas with peritoneal dissemination responding to gemcitabine.

Mucinous cystic neoplasm(MCN)of the pancreas is a rare disease. A 34-year-old female was referred to our hospital for a giant cystic tumor in the left epigastrium, suspected of being a pancreatic MCN. The surgical findings revealed that the tumor originated in the pancreatic tail with the presence of peritoneal dissemination. A distal pancreatectomy and a splenectomy were performed, and the resected specimen histologically revealed an invasive mucinous cystadenocarcinoma of the pancreas. The postoperative computed tomography(CT)scan showed metastatic tumors of the Douglas pouch and the left ovary. Gemcitabine(GEM)was thereafter systemically administered for palliative chemotherapy with a regimen of 1,000 mg/m / 2week for 3 weeks, followed by a week of rest. When assessed by a CT scan after 4 courses of chemotherapy, marked shrinkage of the tumors was identified, and we could not detect the tumors clearly. Moreover, the serum CA19-9 level fell from 341 U/mL to almost normal and there were no severe adverse events. Therefore, systemic chemotherapy with GEM is considered to possibly be an effective treatment against MCN. We describe herein the first case of advanced mucinous cystadenocarcinoma of the pancreas with peritoneal dissemination responding to GEM and a brief review of the literature.

Carcinosarcoma of the gallbladder producing alpha-fetoprotein and manifesting as leukocytosis with elevated serum granulocyte colony-stimulating factor: report of a case.

A 69-year-old man was referred to our hospital for investigation of leukocytosis and a persistent fever of 38 degrees C, but we could find no evidence of a specific infection. The leukocyte count was 18,000/mm(3), and the serum granulocyte colony-stimulating factor (G-CSF) and alpha-fetoprotein (AFP) levels were both elevated, at 66.3 pg/ml and 1,495 ng/ml, respectively. Computed tomography (CT) showed a gallbladder tumor and we performed extended cholecystectomy. Postoperatively, the fever subsided and the leukocyte count, serum G-CSF and AFP level normalized. Histologically, the tumor was a carcinosarcoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for AFP, but negative for G-CSF. This is the first report of a carcinosarcoma of the gallbladder producing AFP. The laboratory findings and clinical course strongly suggested that the tumor produced not only AFP, but also G-CSF.

[Multidisciplinary strategy for lung cancer patients with bone metastasis].

The fall of QOL by bone metastasis poses a problem with the increase in lung cancer. The examples of long-term survival of lung cancer are also increasing by progress of chemotherapy or molecular-targeted therapy. Now, in addition to the conventional radiotherapy, the multidisciplinary treatment including a newer bisphosphonates or an orthopedic operation has been needed to bone metastasis of lung cancer. We presented the lung cancer case who showed the symptoms in transcervical pathologic fracture and whose QOL was improved by orthopedic surgery, radiotherapy to bone metastasis, chemotherapy, gamma knife surgery, and treatment with zoledronic acid and gefitinib.

Huge thymoma: role of preoperative WHO histological classification.

A 57-year-old woman was admitted to our hospital with complaints of recent onset of dyspnea on exertion. A chest computed tomography revealed a large mediastinal mass which extrinsically compressed the heart and mediastinal structures, occupying one half of the hemithorax. A needle biopsy was performed to find a thymoma with type AB according to the WHO classification. Based on the radiological and histological finding a surgery for the tumor was achieved by exploratory VATS thoracotomy followed by thymectomy through a median sternotomy with tumor extirpation of 910 g in weight. A definite diagnosis of thymoma (Masaoka I) without capsular invasion was obtained from the pathologic findings, including positive immunohistochemical staining for CD1a and cytokeratin.

Fall in diffusing capacity associated with induction therapy for lung cancer: a predictor of postoperative complication?

BACKGROUND: Pulmonary resection after induction therapy is associated with high rates of pulmonary morbidity and mortality. However, the impact of induction therapy on the pulmonary toxicity and associated pulmonary complications has not been fully investigated in the setting of lung cancer surgery. METHODS: We assessed the 66 consecutive patients who underwent a pulmonary resection after induction therapy, 48 of whom received chemoradiotherapy and 18, chemotherapy alone. Results of pulmonary function before and after induction therapy were compared, and logistic regression analyses utilized to explore the risk factors of pulmonary morbidity. RESULTS: After induction therapy, forced expiratory volume in 1 second (FEV1) was increased significantly (from 2.28 +/- 0.61 L to 2.40 +/- 0.62 L; p < 0.05); however, percent vital capacity (%VC) and FEV1/FVC did not change significantly. The diffusing capacity of lung for carbon monoxide (D(LCO)) was decreased significantly by 21% (from 90.3% +/- 18.3% to 71.1% +/- 12.5%; p < 0.0005). Patients with respiratory complication showed lower predicted postoperative %FEV1 (49.5% +/- 11.1% versus 57.2% +/- 14.2%; p = 0.031) and predicted postoperative %Dlco (41.9% +/- 8.0% versus 55.4% +/- 10.1%; p < 0.0001) results than those without complications. Univariate and multivariate analyses revealed that predicted postoperative %D(LCO) alone was an independent factor to predict postoperative pulmonary morbidity. CONCLUSIONS: For patients who undergo a pulmonary resection after induction therapy, predicted postoperative %D(LCO) is more important to predict pulmonary morbidity rather than static pulmonary function (predicted postoperative %VC or %FEV1). The decrease in D(LCO) is thought to reflect a limited gas exchange reserve, caused by the potential toxicity of chemotherapy or chemoradiotherapy. We believe that the impact of diffusion limitation after induction therapy should to be emphasized to decrease the pulmonary morbidity.

Clinical impact of concomitant surgical diagnosis and subsequent lobectomy for preoperatively undiagnosed lung cancer.

OBJECTIVES: We conducted a retrospective study of the clinical impact of a concomitant diagnostic and therapeutic procedure for patients with histologically unproven pulmonary nodules. METHODS: Between January 2001 and December 2003, we performed 150 consecutive surgical biopsy procedures for histologically indeterminate pulmonary nodules. We compared the clinical impact of the concomitant diagnostic wedge resection followed by lobectomy (U group, n=50) with that of a scheduled standard lobectomy in those with preoperatively proven clinical stage I lung cancer during the same period (C group, n=60). RESULTS: There were no significant differences in dichotomous variables, whereas we found significant differences in tumor size, operative time and blood loss between the 2 groups. Complication developed in 9 in the U group and 3 in the C group (p=0.030). Hospital mortality was 2% in the U group and 0% in the C group (p=0.11). CONCLUSION: Morbidity and mortality following a concomitant diagnostic and therapeutic procedure in patients with preoperatively undiagnosed lung cancer was acceptable, however, staged operations should be indicated for patients with considerable co-morbidity.

Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer: trends over time and 20-year institutional experience.

OBJECTIVE: Sleeve lobectomy is a lung-saving procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study was to report the clinical characteristics, operative results, survival, and late outcomes over 20 years in patients who underwent sleeve lobectomy and pneumonectomy at our institution. METHODS: There were 62 patients who underwent sleeve lobectomy (SL group) and 110 who underwent pneumonectomy (PN group). Comparisons of the demographics, morbidity, and survivals between the groups were performed by unpaired t-test, chi(2)-test, and log-rank test. RESULTS: Patients who underwent a pneumonectomy showed a significantly advanced pathological stage, and a larger tumor size than those who received a sleeve lobectomy, whereas there were no significant differences in histology, ratio of combined resection and induction therapy, or total morbidity. There were three in-hospital deaths (4.8%) in the SL group and four (3.6%) in the PN group. Local relapse and distant recurrence incidence were similar between the two groups. The 5-year-survival rates of the SL and PN groups were 54% and 33%, respectively (p<0.0001). However, there were no differences in 5-year survivals in patients with pathological stage I/II (SL, 59% vs PN, 63%) and those who received induction therapy (SL, 22% vs PN, 52%) between the groups. CONCLUSIONS: Both pneumonectomy and sleeve lobectomy were performed with an acceptable risk of operative mortality and satisfactory 5-year survival rate. The indication of pneumonectomy is aimed to perform a curative resection for locally advanced lung cancer, particularly after induction therapy that is otherwise unresectable, and the selected patients will likely benefit from a complete resection.

M-tip electro-ablation of pneumo-cysts for treatment of spontaneous pneumothorax as a secondary method to stapling: a confirmation study.

BACKGROUND: We recently established new guidelines for our electro-ablation technique, which has been shown to be a ubiquitous, easy, and cost effective method secondary to stapled resection of pneumo-cysts for the treatment of pneumothorax. The present study was conducted as a confirmation of the effectiveness of this technique. PATIENTS AND METHODS: Between July 1998 and June 2003, 164 consecutive patients with spontaneous pneumothorax underwent surgery. Dependent lesions were resected using staplers. If found, residual lesions were ablated using M-tip electro-ablation (Group M). When the ablated pneumo-cysts were greater than 2 cm in diameter, pleural treatment was carried out by covering the surface with absorbable mesh sheets (Group L). RESULTS: There were 7 cases (4.2%) of relapse of spontaneous pneumothorax and each underwent another operation due to the relapse. None of the lesions in the relapse cases received electro-ablation in the first operation. Relapse-free cases were 97/103 (94%) in Group N (no ablation group), 48/49 (98%) in Group M, and 12/12 (100%) in Group L (P=0.4). COMMENTS: Our results demonstrated the safety and efficacy of our M-tip electro-ablation technique for pneumo-cysts as a secondary method to stapling. We considered that it was feasible for the treatment of spontaneous pneumothorax.

Persistent cough following pulmonary resection: observational and empiric study of possible causes.

BACKGROUND: Following thoracic surgery, patients often suffer from persistent coughing. There is speculation regarding the cause. However, since few studies of that following pulmonary resection have been reported, we conducted an observational and empiric study of this issue. METHODS: A cross-sectional assessment of 240 patients who had undergone a pulmonary resection was performed using a questionnaire regarding postsurgical persistent coughing. Further, therapy based on empiric results was given to 20 patients who had undergone a lobectomy and mediastinal lymph node resection for nonsmall cell lung cancer. RESULTS: Seventy patients were surveyed within 1 year following surgery (subchronic phase), of whom 35 (50%) suffered from coughing, as compared to 30 (18%) of 170 whose postoperative time was 1 year or more (p < 0.0001). Presence of lung cancer, mediastinal lymph node resection, and gastroesophageal reflux (GER) symptoms were significant factors in the group of subchronic patients. Of the 20 patients who received empiric therapy, 90% saw their coughing symptoms improve after the course of medication. CONCLUSIONS: In the present patients, mediastinal lymph node resection may have contributed to coughing after the procedure, which tended to improve after 1 year following the operation. Further, a secondary change, such as GER, caused by surgical intervention may also be a contributing factor in the subchronic phase.

Postoperative serum carcinoembryonic antigen levels in patients with pathologic stage IA nonsmall cell lung carcinoma: subnormal levels as an indicator of favorable prognosis.

BACKGROUND: Elevated serum carcinoembryonic antigen (CEA) levels are sometimes attributable to the production of CEA by malignant cells, and in turn, the antigen itself can enhance the metastatic potential of malignant cells. The authors speculated that low serum CEA levels might be indicative of relatively low levels of malignant cells and a low probability of disease recurrence. This hypothesis led them to investigate whether low CEA levels in serum represented a useful prognostic factor for patients with pathologic Stage IA nonsmall cell lung carcinoma. METHODS: Between 1993 and 2001, 724 patients underwent surgery for NSCLC at Toneyama National Hospital (Toyonaka, Japan). Of these patients, the 242 who were diagnosed with pathologic Stage IA disease were included in the current study. Smoking behavior, gender, age, tumor diameter, disease histology, and preoperative and postoperative serum CEA levels were chosen as study variables, with the cutoff level between subnormal and normal serum CEA levels set at 2.5 ng/mL and the cutoff level between normal and high serum CEA levels set at 5.0 ng/mL. Prognostic indicators were evaluated using a Cox hazard model. In addition, survival probabilities were calculated using the Kaplan-Meier method, and differences in survival were assessed by log-lank analysis. RESULTS: Subnormal postoperative serum CEA levels were found to be an independent prognostic indicator (hazard ratio, 2.3; 95% confidence interval, 1.1-4.7; P = 0.03 for comparison with patients who had normal CEA levels) on multivariate analysis. Furthermore, the 5-year survival rate was 87% for patients with subnormal postoperative CEA levels (n = 146), compared with 75% for patients with normal postoperative CEA levels (n = 80) and 53% for patients with high postoperative CEA levels (n = 16) (P < 0.0001). CONCLUSIONS: Among patients with pathologic Stage IA NSCLC, those who had an extremely favorable prognosis were distinguished by their subnormal postoperative serum CEA levels.

Thymic carcinoma. Clinical institutional experience with 15 patients.

OBJECTIVE: We retrospectively evaluated 15 patients with thymic carcinoma treated with various modalities and investigated overall management of this disease. METHODS: From 1983 to 2003, we treated 15 patients with thymic carcinoma (12 squamous cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma). According to Masaoka's staging system, they consisted of 2 at stage II, 5 at stage III, 4 at stage IVa and 4 at stage IVb. RESULTS: Ten patients were histologically diagnosed preoperatively, and 5 patients underwent an exploratory procedure under the diagnosis of thymoma or benign teratoma. Complete resection was performed in 9 patients (2 stage II, 5 stage III and 2 stage IVa), which included 4 patients who received induction therapy, 4 who received postoperative radiation therapy, and 1 who received postoperative chemotherapy. Six patients with unresectable tumors were treated by irradiation (40-60 Gy) with or without chemotherapy. The median survival was 13 months for patients without resection, and 57 months for patients with a complete resection. Total 3-year and 5-year survival rates were 51.9 and 39.0%, respectively. CONCLUSIONS: We concluded that a complete resection is mainstay of therapy when possible, but chemoradiation therapy being potential benefit in the management of thymic carcinoma. However, considering the high prevalence of advanced stage patients, to establish the effective regimen of induction therapy in the additional multicenter trials should be mandatory.

The possibility of reducing xenoantigen levels with a novel gal 3'-sulfotransferase (GP3ST).

Glycoprotein-3-sulfotransferase (GP3ST) is a key enzyme in downregulating the expression of Galalpha1,3Galbeta1,4GlcNAc-R (the alpha-Gal epitope), via enzymatic competition with an alpha1,3 galactosyltransferase (alpha1,3GT), such as alpha2,6 sialyltransferase (alpha2,6ST). In this study, we report the dominance of GP3ST over alpha1,3GT using transfected pig endothelial cell (PEC) lines. The introduction of the GP3ST gene into PEC suppresses its antigenicity with respect to normal human pooled serum (NHS), including the alpha-Gal epitope and the Hanganutziu-Deicher (H-D) antigen, and, in addition, reduces the susceptibility to NHS in complement-mediated cell lysis. Western and lectin blot analyses of the products of parental PEC and its transfectants indicated that proteins smaller than 66 kDa have a diminished reactivity with NHS and the IB4 lectin. The levels of the alpha-Gal epitope in neutral glycosphingolipids were also decreased in the GP3ST transfectants as detected in thin layer chromatography by immunostaining. These data indicate that GP3ST is very effective in reducing xenoepitope levels.