[A Case of Recurrent Lung Adenocarcinoma with Right Aortic Arch Treated with Pembrolizumab].

Only a few cases of primary lung cancer associated with the right aortic arch have been reported. A treatment report of recurrent lung cancer with the right aortic arch is rare. A woman in her late 70s was diagnosed with lung cancer associated with the right aortic arch. A 3.4-cm tumor was detected in the right middle lobe on CT performed before a knee joint surgery. The tumor was diagnosed as lung adenocarcinoma and categorized as cT2aN0M0 with cStage ⅠB. Subsequently, a right middle lobectomy was performed. Histopathological study revealed pT1cN1M0 with pStage ⅡB tumor. Molecular analysis revealed 85% expression of programmed death-ligand 1(PD-L1). One year after surgery, mediastinal lymph nodes recurred with multiple lung metastases. The number of metastatic lymph nodes reduced after pembrolizumab was administered, followed by the disappearance of lung metastasis. The outcome was recorded as a partial response. She has been alive 2 years after surgery.

Safety of salvage lung resection after immunotherapy for unresectable non-small cell lung cancer.

BACKGROUND: The safety of salvage lung resection after immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC) is not well understood. METHODS: In this retrospective multicenter study, we reviewed perioperative morbidity and mortality rates in 11 patients (8 men, 3 women; median age 70 years) who underwent salvage lung resection for unresectable NSCLC after ICI therapy in the 4 years since 2017. Operative factors were also compared according to operating time (> 6 h, n = 7; < 6 h, n = 4). RESULTS: The clinical stage at the time of diagnosis was IIIA in 2 patients, IIIB in 4, IVA in 2, and IVB in 3. Eight patients received pembrolizumab and 3 received durvalumab. Two patients received an ICI agent alone, 3 underwent chemoradiotherapy, and 6 received chemotherapy. Lobectomy was performed in 10 cases and bilobectomy in 1 case. All patients underwent complete resection. Median operating time was 429 (range 169-570) min with a median blood loss of 199 (range 10-5, 140) mL. The only intraoperative complication was damage to the pulmonary artery. The perioperative morbidity and mortality rates were 27% and 0%, respectively. The 90-day mortality rate was 9% (1 patient died of acute exacerbation of interstitial pneumonia). Patients in whom the operating time was > 6 h more frequently had lymph node metastasis at the time of initial diagnosis (100% vs 25%, p = 0.02). CONCLUSIONS: Salvage lung resection was tolerated after ICI therapy in these patients. Lymph node metastasis at the time of initial diagnosis might make salvage surgery difficult.

[Nivolumab Therapy for Synchronous Double Primary Lung and Gastric Cancers].

A 70-year-old man who was diagnosed with a cStage ⅣA lung adenocarcinoma was in a stable condition for a long time after the first chemotherapy with gefitinib. However, 2 years 4 months later, the lung cancer progressed, and he was diagnosed with Stage Ⅲ gastric cancer. Since the administration of afatinib as the second-line chemotherapy was ineffective, nivolumab was administered as the third-line chemotherapy. The lung cancer showed a partial response to nivolumab treatment, but the gastric cancer remained unresponsive. We report a rare case of immune checkpoint inhibitor administration for synchronous double primary cancers.

[A Case of Recurrent Thymoma Treated with Pembrolizumab as the Fifth-Line Chemotherapy].

The option of chemotherapy for recurrent thymoma is limited. Postoperative adjuvant therapy has yet to be established. A 71-year-old male underwent extended thymectomy for thymoma with Masaoka stage Ⅲ, and subsequently, radiation was performed as adjuvant therapy in 2012. Since recurrence was detected in 2014, multidisciplinary treatment was performed for 4 years. An increase of intrathoracic dissemination was detected in 2018. Tumor tissue samples by re-biopsy showed 70% expression of programmed death-ligand 1(PD-L1). Pembrolizumab was administered as fifth-line chemotherapy every 4 weeks at a dosage of 200 mg. After 3 courses, the lesions had remarkably decreased. This suggests that pembrolizumab for thymoma with high PD-L1 expression is efficacious.

Immunohistochemical analyses of a case of extralobar pulmonary sequestration with chest pain in an adult.

Computed tomography of a Japanese man in his mid-forties with a complaint of right-side chest pain showed a dome-shaped smooth-surfaced mediastinal mass, which was extirpated. The cut surface was highly hemorrhagic and necrotic and not related to the original pulmonary tissues. Although routine sectioning detected bronchial cartilage, immunohistochemical analyses clearly showed the presence of alveolar type II cells; only the alveolar type II cells located at the periphery of this mass showed positive staining for cytokeratins, thyroid transcription factor 1, surfactant protein A, epithelial membrane antigen and Krebs von den Lungen-6. Thus, these analyses are useful for the detection of pulmonary components, even in severely hemorrhagic and necrotic tissues with marked sequestration. The clinical diagnosis was a rare, adult type of extralobar pulmonary sequestration accompanied by chest pain.

[First reported case of lung metastasis from hepatocellular carcinoma successfully treated by ultrasound-guided radiofrequency ablation using ultrasonic contrast agent].

BACKGROUND: Radiofrequency ablation (RFA) is becoming one of the useful options as a local control therapy for lung cancer. Almost all reported cases according to the RFA for lung cancer were performed by CT -guided technique. Only a limited number of articles have been published on ultrasound-guided RFA for lung cancer. CASE: An 80-year-old man underwent transcatheter arterial embolization (TAE) and RFA for hepatocellular carcinoma (HCC) in 2004. A 3.3 cm pulmonary nodule was pointed out in his right lower lobe on a chest CT examination in 2007. The nodule was diagnosed as a lung metastasis from HCC by core needle biopsy. He underwent CT-guided RFA. After three months, the lung metastasis progressed in the same location on the enhanced CT. Then an ultrasound-guided RFA using ultrasonic contrast agent (Sonazoid) was performed. We could distinguish between the necrotic lesion and the viable lesion using Sonazoid, and selective RFA for viable lesion became possible. CONCLUSION: Sonazoid has been highly evaluated in the ultrasound-guided RFA for HCC. To the best of our knowledge, this is the first report of a lung cancer case successfully treated with ultrasound-guided RFA using Sonazoid.

A rare case of coexistence of pulmonary adenocarcinoma with Langerhans' cell histiocytosis.

We report a rare case of coexisting pulmonary adenocarcinoma and Langerhans' cell histiocytosis (LCH) in a 78-year-old woman who did not smoke. During follow-up of diabetes mellitus, she had complained of chest pain and was found to have a nodular lesion in S9 of the left lower lobe, which was resected surgically. No abnormal laboratory findings were obtained. Before surgical resection, needle biopsy specimens confirmed the existence of adenocarcinoma. The resected tumor in the left lower lobe was 3.0 x 1.8 x 3.0 cm, and histologically both acinar and bronchioloalveolar cell subtypes of adenocarcinoma were found in cancer foci. In addition to pulmonary adenocarcinoma, Langerhans' cell proliferation associated with marked eosinophil infiltration was incidentally found in a small nodule, approximately 3 x 2 mm in size in the subpleural region. The Langerhans' cells contained interdigitated nuclei, exhibiting rather clear nucleoplasm and cytoplasm; they were positive for S-100 protein, CD1a, and also CD4. Massive eosinophil infiltration was found around the focus of Langerhans' cell proliferation. This nodule appeared to be LCH. The adenocarcinoma and LCH were adjacent, and cancer cells were infiltrated only in the peripheral parts of LCH. The coexistence of adenocarcinoma and LCH appeared to be incidental. The association of adenocarcinoma and LCH is rare, and only several reports of it can be found in the English literature.

[A case of triple negative recurrent breast cancer successfully treated with capecitabine+docetaxel combination chemotherapy].

A 73-year-old woman underwent pectoralis-preserving mastectomy for left breast cancer (papillotubular carcinoma, f, T2, ly0, v0, N1 (21/21), T2N1M0 (Stage IIB), ER (-), PgR (-), HER2 (-)) in August 2004. It was called a triple negative breast cancer. She received systemic chemotherapy using AC followed by paclitaxel. In February 2006 (disease- free interval of one year and five months), skin and chest wall recurrences in the left breast were revealed. Systemic chemotherapy using capecitabine (1,800 mg/body/day) monotherapy resulted in PD after 4 courses. Subsequently, treatment with capecitabine+cyclophosphamide combination therapy resulted in PD after 6 courses. Since November 2006, treatment with capecitabine+docetaxel combination chemotherapy was initiated. Each course consisted of capecitabine at a dosage of 1,800 mg/body/day for 2 weeks and docetaxel at a dosage of 60 mg/body (day 8 only) followed by withdrawal for 1 week. After 3 courses, a marked response was seen, and a total of 6 courses were performed. No serious side effect was revealed, and a marked response has been maintained. It is suspected that capecitabine+docetaxel combination therapy is useful for a triple negative recurrent breast cancer which is refractory to systemic chemotherapy.

Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia.

To clarify the localization of KL-6 and epithelial membrane antigen (EMA) in human lungs, immune reactions to antibodies to these factors were examined in detail at light and electron microscopic levels. Immunohistochemical investigation was performed in 17 cases of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP), collagen vascular disease-associated interstitial pneumonias (CVD-IP), viral pneumonia, and bronchobronchioloectasis, as well as in 10 cases of presumably normal pulmonary tissue resected as a result of spontaneous pneumothorax. Immunohistochemical study revealed similar discontinuous linear or dome-shaped positive patterns restricted to type II alveolar cells in presumably normal tissue and only some regions of interstitial pneumonia. In sharp contrast, immune reactions with each of the two antibodies yielded a continuous linear pattern surrounding damaged areas in most regions of interstitial pneumonias and some normal areas as well. Staining for EMA antibody was negative in some regenerating alveolar and bronchial cells in regenerating foci in interstitial pneumonias, although staining for KL-6 antibody was always positive in these cells. Immunoelectron microscopic studies demonstrated similar positive reactions with both antibodies on the surface of alveolar epithelial cells in three of the cases examined, with surface positive granules 100-200 nm in diameter. Thus, although staining for both KL-6 and EMA antibodies exhibited discontinuous positivity restricted to type II alveolar cells in nondamaged regions, immune reactions were continuous and linear in pattern in or around damaged areas of the lungs at both light and electron microscopic levels, probably as a consequence of cell-surface barrier function. These findings in pulmonary tissue might be evidence of defense functions.

Ultrastructural study of nuclear inclusions immunohistochemically positive for surfactant protein A in pulmonary adenocarcinoma with special reference to their morphogenesis.

To investigate the fine-structural nature of nuclear inclusions immunopositive for surfactant protein A (SP-A) antibody staining, a detailed ultrastructural study was performed, as well as immunohistochemical examination of pulmonary adenocarcinomas. Surgically resected tumor specimens from 31 patients were examined by immunohistochemistry focused on reactivity to SP-A and thyroid transcription factor 1 (TTF-1) antibodies. Only cases with >5% positive nuclear inclusions in cancer cells were considered positive, some of which were examined by electron microscopy. Immunohistochemically, 6 of 31 cases were doubly positive for SP-A and TTF-1 antibodies. On electron microscopy, SP-A-positive nuclei contained diffuse or globular fine granular substance as inclusions. Both types of globular and diffuse inclusions were sometimes connected to the inner nuclear membrane, in association with fragmented or stacked membranous structures. The findings of this study suggested that nuclear inclusions positive for SP-A antibody staining in adenocarcinomas of the lung were derived from accumulated content in the perinuclear cistern resembling pseudoinclusion processes and composed of proteins antigenically cross-reactive with SP-A.

[Results of treatment of far advanced and recurrent stomach cancer with TS-1].

We used TS-1 as first-line therapy to treat 44 patients with far advanced or recurrent gastric cancer, and assessed the results and safety. One treatment cycle consisted of TS-1, 80 mg/m2/day, for 28 days followed by a 14-day rest period. The efficacy rate in the cases capable of being evaluated was 30.1% (11/36), and 25.0%, (7/28) when TS-1 was used as monotherapy. The efficacy rate was lower than in a phase II study, however, the median survival time (MST) of 10.7 months for the patients as a whole, the 1-year survival rate of 43.2%, and the 2-year survival rate of 20.5% were favorable. There were many NC cases in which long-term therapy was possible, and they contributed to the long-term survival. The incidence of adverse events was 84.1%, but the incidence of grade 3 or more events was low at 13.6%. Since TS-1 is highly efficacious and safe, as well as convenient because of being an oral preparation, it appears that it can be ranked as the drug of first choice for chemotherapy of far advanced or recurrent gastric cancer.