[An autopsy of a case of pulmonary hypertension secondary to pulmonary embolization of intrahepatic cholangiocarcinoma].

A 70-year-old woman was admitted to our hospital for one month because of progressive dyspnea. Her medical history included an operation for hepatolithiasis at age 47. She was a current smoker. Chest CT revealed emphysematous change and honeycombing in the lung and bilateral subpleural opacifications. Cardiac ultrasound examination showed pulmonary hypertension. Treatments with antibiotics, corticosteroids and heparin were unsuccessful. Despite mechanical ventilation, she died of respiratory failure. Autopsy revealed that intrahepatic cholangiocarcinoma had spread via the hematogeneous route, formed multiple emboli into the pulmonary small arteries, and led to severe pulmonary hypertension and lung infarction.

[Retrospective analysis of immediate cause of death in lung cancer-two case reports of lung cancer deaths due to bowel necrosis].

The immediate cause of death of 313 patients who died of lung cancer during 5 years in this center was analyzed. The specific, immediate causes of the 313 deaths were respiratory failure 34. 8%, pneumonia 19. 0%, cachexia 12. 0%, and brain metastasis 8. 3%. Digestive organ disease deaths were 7. 0%(22 patients), being the 5th-ranking immediate cause of death. Of these 22 cases, hepatic insufficiency death by liver metastasis was in 10 out of 22 cases, and gastrointestinal bleeding was in 8 cases. Two patients died of intestinal tract necrosis, but the direct causal relationship between the cause of death and the tumor was unconfirmed from the autopsy result. However, we speculated that an elderly, tumor-bearing condition combined with chemotherapy led to prolonged immobility, a poor nutritional state, and rapid weight loss, which could be influential on the bowel necrosis.

EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors.

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.).

A phase II study directed by a clinical pathway for carboplatin and weekly paclitaxel in previously untreated patients with unresectable non-small cell lung cancer.

The objective of this phase II study was to evaluate the efficacy and safety of carboplatin and weekly paclitaxel in previously untreated patients with unresectable non-small cell lung cancer. In addition, the clinical pathway intensified the management of chemotherapy including the assessment of efficacy, safety and implementation of treatment and patient education. Patients received paclitaxel at a dose of 70 mg/m(2) on days 1, 8 and 15 and carboplatin (area under the curve of 6) on day 1 and every 28th day thereafter. Fifty-eight patients were enrolled. A median of 3 cycles (range 1-6) were administered. Twenty-eight cases showed objective responses (48.2%), including 2 complete (3.4%) and 26 partial responses (44.8%; 95% confidence interval 35.4-61.1). The median survival time was 663 days, and the 1-year survival rate was 59.9%. Nineteen patients (32.8%) had grade 3, and 4 patients (6.9%) had grade 4 neutropenia. Nine patients (15.5%) experienced > or =3 grade nonhematological toxicities. There were no treatment-related deaths due to this study. Carboplatin and weekly paclitaxel combination chemotherapy might be an alternative treatment selection in patients with unresectable non-small cell lung cancer.

[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.

Pyothorax-associated lymphoma: an unusual case with both T- and B-cell genotypes.

Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma which develops in the pleural cavity of patients with an over-20-year history of pyothorax. Aberrant expression of surface antigens is occasional in PAL, although genotype is not fully investigated. We report here a PAL with dual genotype, i.e., simultaneous immunoglobin (Ig) and T-cell receptor (TcR) gene rearrangement. An 82-year-old woman with pain on the left side of the chest was admitted. She had been suffering from pyothorax after artificial pneumothorax for treatment of tuberculosis of the pulmonary when she was 18 years old. The mass that was confined to the left pleural cavity affected by pyothorax was biopsied and histologically diagnosed as diffuse large cell lymphoma. The tumor cells were positive for CD20, CD16, and TIA-1 but negative for CD79a, CD45RO, CD43, CD3, and CD56. Surface antigen expression was further investigated in cultured cells, showing that the cultured cells did not express representative B-cell markers, except for CD20, as well as T-cell markers, but were positive for CD16, CD30, and CD103. Southern blotting revealed the monoclonally rearranged bands of both Ig heavy chain and TcR gene. The patients died of tumors 14 months after admission. Aberrant genotype and immunophenotype of PAL cells is discussed in reviewing the pertinent literature.

[Chemotherapy for small-cell lung cancer (SCLC) patients with renal failure].

We administered chemotherapy in three cases of small-cell lung cancer (SCLC) with renal failure under different situations. Hemodialysis (HD) was used in 2 out of the 3 cases. Case 1 was complicated by acute renal failure from extensive bilateral tumor invasion. After chemotherapy (CBDCA + ETP) under HD, renal metastases regressed and renal function improved, although the final response was PD. In case 2, HD had been introduced for diabetic nephropathy. After 2 cycles of chemotherapy (CBDCA + ETP) under HD, the patient attained a PR. Case 3 is an example of paraneoplastic nephrotic syndrome with renal failure. Chemotherapy including CBDCA or CDDP was performed and the QOL of the patient improved. Pro-GRP and serum creatinine changed in parallel during the clinical course of 6 admissions. In conclusion, individualized therapy is necessary to increase survival time of SCLC patients with renal failure. Although chemotherapy is useful, further study is needed for the selection of suitable chemotherapeutic regimens, optimal dosage of each drug and the timing of HD.