[Clinical Significance of Placing a PEG during Chemoradiotherapy for Advanced Esophageal Cancer].

BACKGROUND: Unresectable advanced esophageal cancer is often treated with chemotherapy or chemoradiotherapy(CRT). Nutritional disorders caused by dysphagia may lead to a poor prognosis. Placing a PEG before starting CRT for advanced esophageal cancer may maintain better nutritional status. PURPOSE: The purpose of this study is to evaluate the clinical significance of placing a PEG before starting CRT for advanced esophageal cancer. RESULTS: Fifty-one cases were evaluated, 22 PEG (+) and 29 PEG (-). The rate of a CRT was better in PEG (+) than PEG (-) cases (91% vs 79%). Infection around the PEG was the only type of complication, affecting 5%. CONCLUSION: PEG feeding during CRT is important in the development of effective treatments for unresectable advanced esophageal cancer.

[A case of synchronous sigmoid cancer and ureter cancer].

A 78-year-old-man visited a nearby doctor for treatment of hepatitis C and high blood pressure.He was diagnosed with right hydronephrosis by abdominal echography conducted in follow-up of hepatitis C treatment in November 2011; he was then introduced to our hospital for close inspection and medical treatment.We observed wall hyperplasia and narrowing of the lumen in the central sigmoid part by contrast-enhanced computed tomography (CT).The right ureter at the L4/5 level showed wall hyperplasia and a deep color, and the right ureter, renal pelvis, and calix were expanded on the head side. By examination for CF, we observed a type 2 lesion in the sigmoid colon, and a biopsy showed well-differentiated adenocarcinoma. Based upon these findings, he was diagnosed with synchronous sigmoid colon cancer (cT4aN0M0, cStage II) and ureter cancer (cT2N0M0, cStage II); we performed laparotomy sigmoidectomy(D3 dissection)and full extraction of the right kidney urinary tract (lymph node dissection in front of the vena cava, the latter outside and between the aorta and vena cava). The postoperative course was particularly uneventful, and the patient was discharged from the hospital on day 38 after the operation. More than 2 years after the surgery, the patient exhibits no sign of sigmoid colon cancer or ureter cancer recurrence.

[Occurrence of squamous cell lung carcinoma in the irradiated field after radiotherapy for breast cancer].

Radiotherapy for breast cancer reduces the incidence of disease recurrence and breast cancer mortality.However, it has also been associated with an increased risk of developing secondary cancers in exposed sites.Recently, we observed a 64-year-old woman who developed squamous cell lung carcinoma in the field irradiated with a total dose of 55 Gy after conservative breast surgery for left breast cancer 16 years previously.The patient underwent left upper lobectomy combined with chest wall resection.She had no recurrence of the breast cancer for 16 years.The secondary lung cancer tumor was of a different histological type than the primary breast cancer, and it appeared in the irradiated field.In conclusion, we regarded her lung cancer as a radiation-induced cancer, although it is difficult to clearly define radiation-induced cancer.In addition, the patient 's lung cancer may not only be a result of the late effect of irradiation, but might also be due to her smoking habit.

[A long-term survivor of a rectal carcinoid treated by use of repeat TACE for multiple intrahepatic recurrences after liver resection and MCT].

A woman between 50 and 60 years of age was diagnosed with a rectal carcinoid tumor and synchronal multiple liver metastases. We performed a transanal local resection of the rectal tumor, which was 10mm in diameter. During surgery, ultrasonography revealed 8 hypoechoic masses in the liver, and we performed a partial hepatectomy (S5/6, S8) and administered microwave coagulation therapy. Thirty-seven months after surgery, abdominal computed tomography revealed multiple low-density tumors in the bilateral lobe of the liver. We diagnosed these tumors as a recurrence of the liver metastases of the rectal carcinoid and performed trans-arterial chemo-embolization (TACE). After repeated TACE treatments, the liver metastases were controlled favorably. The patient is alive more than 50 months after diagnosis of the recurrent liver metastases. TACE appears to be effective for treating non-resectable multiple liver metastases of rectal carcinoids.

CD98 heavy chain protein is overexpressed in non-small cell lung cancer and is a potential target for CAR T-cell therapy.

Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.

Three-Dimensional Idiopathic Pulmonary Fibrosis Model Using a Layer-by-Layer Cell Coating Technique.

Idiopathic pulmonary fibrosis (IPF) is a severe health problem characterized by progressive fibroblast proliferation and aberrant vascular remodeling. However, the lack of a suitable in vitro model that replicates cell-specific changes in IPF tissue is a crucial issue. Three-dimensional (3D) cell cultures allow the mimicking of cell-specific functions, facilitating development of novel antifibrosis drugs. We have established a layer-by-layer (LbL) cell coating technique that enables the construction of 3D tissue and also vascularized 3D tissue. This study evaluated whether this technique is beneficial for constructing an in vitro IPF-3D model using human lung fibroblasts and microvascular endothelial cells. We fabricated an in vitro IPF-3D model to provide IPF-derived fibroblasts-specific function and aberrant microvascular structure using the LbL cell coating technique. We also found that this in vitro IPF-3D model showed drug responsiveness to two antifibrosis drugs that have recently been approved worldwide. This in vitro IPF-3D model constructed by a LbL cell coating technique would help in the understanding of fibroblast function and the microvascular environment in IPF and could also be used to predict the efficacy of novel antifibrosis drugs. Impact statement We established a novel in vitro model mimicking idiopathic pulmonary fibrosis. Three-dimensional culture was constructed by layer-by-layer cell coating technique. This novel model provides a visualization of fibroblast-specific function. This assay allows for the assessment of pulmonary microvascular environment. Our model may be useful for predicting the efficacy of novel antifibrosis drugs.

Periostin secreted by activated fibroblasts in idiopathic pulmonary fibrosis promotes tumorigenesis of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients with idiopathic pulmonary fibrosis (IPF) show poor prognosis. Periostin is an extracellular matrix protein highly expressed in the lung tissues of IPF. This study aimed to investigate the possibility that periostin secreted by fibroblasts derived from IPF lung might affect proliferation of NSCLC cells. Periostin was more highly expressed and secreted by fibroblasts from diseased human lung with IPF (DIPF) than by normal human lung fibroblasts (NHLF). Cocultivation of NSCLC cells with conditioned media (CM) from DIPF increased proliferation of NSCLC cells through pErk signaling, with this proliferation attenuated by periostin-neutralizing antibodies. Knockdown of integrin ß3, a subunit of the periostin receptor, in NSCLC cells suppressed proliferation of NSCLC cells promoted by recombinant human periostin and CM of DIPF. On in vivo examination, DIPF promoted tumor progression more than NHLF, and knockdown of integrin ß3 in NSCLC cells suppressed tumor progression promoted by DIPF. Fibroblasts derived from surgical specimens from IPF patients also increased secretion of periostin compared to those from non-IPF patients. Periostin secreted from IPF-activated fibroblasts plays critical roles in the proliferation of NSCLC cells. The present study provides a solid basis for considering periostin-targeted therapy for NSCLC patients with IPF.

Salvage surgery for stage IVa thymic carcinoma combined with aortic arch resection - case report.

BACKGROUND: Although complete surgical resection of thymic carcinoma is a prognostic factor, extended surgery combined with a major blood vessel procedure remains controversial because of the increased risk of mortality. We report a case of Stage IVa thymic carcinoma successfully resected with a pneumonectomy along with aortic arch replacement after chemotherapy. CASE PRESENTATION: A 45-year-old male was diagnosed with thymic carcinoma invasion to the aortic arch and left pulmonary artery. Malignant pericardial effusion was also noted, though disappeared after chemotherapy, thus surgical options were considered. A radical resection procedure including left pneumonectomy, aortic arch replacement with total rerouting of the supra-arch vessels, and right pulmonary artery plication was performed. The postoperative course was uneventful and the patient has been disease-free for 3 years. CONCLUSION: Extended salvage surgery might be a valuable option for advanced thymic carcinoma.

Synchronous primary lung cancer presenting with small cell carcinoma and adenocarcinoma.

Multiple synchronous primary lung cancers presenting with different histologic types are uncommon. Among reported cases with different histologic findings, only a few had small cell lung cancer (SCLC) and adenocarcinoma. This unusual combination of lung cancers has not been well reported. In this report, we describe two cases of synchronous primary lung cancer presenting with lymph node metastasis of SCLC and early-stage adenocarcinoma. Epidermal growth factor receptor (EGFR) mutation was not detected in either SCLC or adenocarcinoma in the two cases.

Successful Removal of Giant Intrapericardial Paraganglioma via Posterolateral Thoracotomy.

Intrapericardial paraganglioma remains a surgical challenge because of its hypervascular nature and firm adhesion to adjacent mediastinal structures. Here, we describe a 63-year-old female with a giant nonfunctioning intrapericardial paraganglioma tightly adhered to the left atrium. Marginal but complete resection of the tumor was achieved via right posterolateral thoracotomy. At the time of dissection between the tumor and the left atrial wall, we encountered massive hemorrhage leading to cardiac arrest. We were able to repair the wall laceration with minimal time under an optimal operative field, which avoids air embolism. She was discharged without complications and is currently in good health with no recurrence or metastasis for 15 months. Based on our experience, cardiopulmonary bypass should be considered, if surgeons are able to secure suitable sites for arterial and venous cannulations while right posterolateral thoracotomy is employed.