Issei Hirai

Increased expression of integrin α3β1 in highly brain metastatic subclone of a human non‐small cell lung cancer cell line

To clarify the roles of integrin and extracellular matrix (ECM) in the process of non‐small cell lung cancer (NSCLC) brain metastasis, we established an in vivo model of brain metastasis of human NSCLC cell line EBC‐1/original in athymic mice, and established highly brain metastatic subclone EBC‐1/brain and highly bone metastatic subclone EBC‐1/bone. Integrin expression of these subclones was evaluated by flow cytometry. In vitro cell attachment, migration and proliferation assays with ECMs were performed using these subclones. Expression of integrin α3 subunit was higher in EBC‐1/brain than in both EBC‐1/original and EBC‐1/bone. In vitro cell attachment, migration, and proliferation assays revealed that EBC‐1/brain had higher affinity and higher reactivity to laminin than EBC‐1/original and EBC‐1/bone. Blocking of integrin α3β1 significantly (P<0.05) decreased brain metastasis by EBC‐1/brain. Interaction of integrin α3β1 and laminin plays important roles in the process of brain metastasis of non‐small cell lung cancer.

Analysis of the early postoperative serum carcinoembryonic antigen time-course as a prognostic tool for bronchogenic carcinoma.

The serum kinetics of carcinoembryonic antigen (CEA) after resection of lung carcinoma are not well characterized. Its prognostic implications remain unclear. This study was designed to clarify the correlation between postoperative CEA time‐course and patient prognosis.

Clinical efficacy of bisphosphonate therapy for bone metastasis from breast cancer

Bisphosphonates inhibit osteoclastic bone resorption and are being used as treatment for bone metastases from breast cancer. Intravenous bisphosphonate therapy can significantly reduce skeletal related events (SREs) when administered concurrently with chemotherapy or endocrine therapy. In addition, intravenous bisphosphonate monotherapy is also able to alleviate cancer induced bone pain, and to improve bone metastases in some patients. Oral bisphosphonates are not routinely used for the treatment of bone metastases due to their low bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than pamidronate, is now in phase II clinical studies in Japan, and may alter the role of oral bisphosphonates in the treatment of bone metastasis from breast cancer. The ASCO guidelines recommend that patients with osteolytic bone metastases be treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate and systemic therapy. In addition, it is also recommended that current standards of care for cancer pain, analgesics and radiotherapy, should not be replaced with bisphosphonate therapy.

A case of serum CEA disappearance curve after resection of breast carcinoma.

Carcinoembryonic antigen (CEA) elimination kinetics after tumor resection were measured in a case of breast cancer. A 45-year-old woman with a left breast carcinoma underwent surgery after neoadjuvant chemotherapy. The serum CEA level before surgery was 34.3 ng/ml. After sequential monitoring of serum CEA levels, postoperative serum CEA elimination kinetics were calculated using non-linear least square analysis with the fitting equation C(t) = (CO — Cp)exp(-kt) + Cp, where C(t) was the postoperative CEA level, t was the number days after surgery, CO was the CEA level at postoperative time zero, Cp was the CEA at plateau, and k was the rate constant of elimination.Cp was calculated as 6.9 ng/ml, which was above the cut-off level and indicated residual malignancy. After adjuvant chemotherapy, CEA normalized to 1.8 ng/ml. In breast cancer patients with high preoperative serum CEA levels, our analytical method for CEA elimination might be useful for the detection of residual malignancies.

Removal of an endobronchial foreign body using an ultrathin flexible bronchoscope and a novel suction system.

To the Editor: Foreign body aspiration in children is a serious condition and a pediatric emergency. If the diagnosis is delayed, complications such as persistent pneumonia, recurrent attacks of bronchospasm, lung abscess, recurrent hemoptysis, and bronchiectasis may develop, necessitating surgical intervention.1 We report a case of a persistent pneumonia of 3 weeks duration in an infant from aspiration of peanuts that was successfully managed by using an ultrathin flexible bronchoscope and a handmade suction system and a balloon catheter. Three weeks before the admission, a healthy 8-monthold boy suffered with productive cough and fever and was diagnosed with acute bronchitis. Despite the medical treatment, his symptoms persisted. A chest computed tomography (CT) scan revealed findings suggestive of a foreign body in the left main bronchus and a left lower lobe pneumonia (Fig. 1A). Under general anesthesia, an ultrathin flexible bronchoscope, 2.2mm in diameter (BFN20; Olympus, Tokyo, Japan) was inserted into the endobronchial tree through the endotracheal tube, 4.5 Fr in diameter. There was a thick white discharge in the left main bronchus and a foreign body, which was a piece of peanut, was observed. The scope was too slim and had no suction port. We made a handmade suction system by placing a small cut over the proximal end of a conventional suction catheter and inserted the bronchoscope into the tubing (Fig. 1B). We attempted to aspirate the foreign body with this modified suction device. However, it resulted in fragmentation of the peanut emitting moderate amount of white discharge from the distal airways (Fig. 1C). A 5.2 Fr balloon angioplasty catheter was then passed by the side of the bronchoscope placing the balloon distal to the foreign body. The balloon was then inflated with air and used to push the foreign body in a retrograde manner (pull). This maneuver allowed the foreign body to be brought proximally without further fragmentation. A split portion of the peanut was easily removed using the suction. (Fig. 1D). Patient’s symptoms promptly resolved, and there was no further recurrence of his pneumonia. Foreign body aspiration is a common pediatric emergency. More than 80% of cases of foreign body aspiration occur during early childhood, with a peak incidence between the ages of 10 and 24 months.2 Only 17.2% of patients with proven foreign bodies did not have an eyewitness to the aspiration episode, and only 20% of foreign bodies are radiopaque. Most of the aspirated foreign bodies in the pediatric age group are food particles, especially nuts or seeds. The diagnosis of a pediatric airway foreign body is more difficult because the patients are unable to communicate and delay in the treatment is not uncommon.3 The bronchoscopic removal of a foreign body among infants is not without challenges as fragmentation or distal migration of the foreign body can occur.4,5 Traditionally, rigid bronchoscopy was the procedure of choice for the removal of foreign bodies in children.6 However, flexible bronchoscopy is increasingly being used for the indication.7,8 Flexible bronchoscope has many advantages compared with rigid bronchoscope. Most importantly, its small diameter and flexibility enable to reach foreign bodies located in distal airways, which are difficult to access with a rigid bronchoscope. Second, flexible bronchoscope may allow simultaneous retrieval of fluids, especially mucus or blood clots, without requiring separate suction catheter.8 When the diagnosis is delayed, such as in our case, and if the foreign body is nuts or seeds, fragmentation is likely with the use of rigid instruments. We always perform the flexible bronchoscopy first before giving consideration to the rigid scope. The weakness of the ultrathin flexible bronchoscope could be the lack of a suction port, as one in our case. Our handmade suction system appeared to be useful to overcome this weak point. Flexible bronchoscopy combined with our handmade suction system and balloon catheter might come handy in similar situations. Disclosure: There is no conflict of interest or other disclosures. LETTERS TO THE EDITOR