Shungo Yukumi

Feasibility of chemohyperthermia with docetaxel-embedded magnetoliposomes as minimally invasive local treatment for cancer

Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel‐embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb‐c/nu/nu mice. Various concentrations of docetaxel‐embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite‐loaded liposome (ML)‐injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43°C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 μg/ml, while a docetaxel concentration > 568.5 μg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent‐embedded magnetoliposomes has an anticancer effect.

Development of a second-generation radiofrequency ablation using sintered MgFe2O4 needles and alternating magnetic field for human cancer therapy

Magnetic metal particles are known to induce heat energy under an alternating magnetic field (AMF). We developed a local tumor-heating device incorporating an MgFe(2)O(4) needle for the purpose of mild ablation for cancer treatment. A needle made from sintered MgFe(2)O(4) particles was embedded in the hepatic or breast tumors. Tumors were then heated by the energy dissipated from the needle exposed to an AMF. We sequentially evaluated histological changes, cellular activity of tumors, and the extent of thermal effect using nicotinamide adenine dinucleotide (NADH) diaphorase and terminal deoxynucleotidyl tranferase-mediated digoxigenin-DUTP nick-end labeling (TUNEL) staining. The mean temperature of the tumor tissue during heating was about 60 degrees C. Nuclei of the tumor cells became hyper-chromatin immediately after heating. The injured area spread progressively until 3 days after heating; when the area was surrounded by fibroblasts (meaning is not clear). Tumors disappeared after treatment without complications. This is the first time that the complete death of tumor cells has been realized by raising the tumor temperature above 60 degrees C using the heat generated by magnetic metal particles exposed to AMF. This device may be useful in the future for local hyperthemic treatment of human cancers.

Repeated inductive heating using a sintered MgFe2O4 needle for minimally invasive local control in breast cancer therapy.

Purpose: This study investigated the efficacy of repeated thermotherapy for breast cancer utilising a novel sintered MgFe2O4 needle and alternating current (AC) magnetic field in xenograft animal models mimicking human breast cancer. Materials and methods: A sintered MgFe2O4 needle and an apparatus to apply an AC magnetic field were prepared for this study. Animals bearing BT-474 tumours (mean (±standard deviation) volume, 471 ± 153 mm3) were divided into four groups. A sintered MgFe2O4 needle (length, 5 mm) was placed in the centre of each tumour. An AC magnetic field (amplitude, 4 kA/m; 2 kW; 540 kHz) was applied for 10 min once, twice or three times for the first, second and third groups, respectively, and was not applied for the control group. Temperature during treatment and tumour volume 8 weeks after first treatment were assessed. Results: Maximum tumour temperature tended to increase in repeated-application groups: group 1, 59.2 ± 4°C; group 2, 58.9 ± 3.3°C and 61.2 ± 8.9°C for the first and second applications; and group 3, 60.4 ± 4.6°C, 62.1 ± 7.8°C and 71.1 ± 6.1°C for the first, second and third applications. Tumour volumes in control, groups 1, 2 and 3 at 8 weeks after treatment were 3633 ± 2478 mm3, 3240 ± 1031 mm3, 1252 ± 1289 mm3 and 0 mm3, respectively. Tumours were significantly smaller in group 3 than in the control and group 1 at 8 weeks. Conclusions: The efficacy of repeated inductive heating utilising a sintered MgFe2O4 needle was demonstrated. Thermotherapy using the present method may offer an effective non-surgical treatment for human breast cancer.

Novel tumor‐ablation device for liver tumors utilizing heat energy generated under an alternating magnetic field

Background and Aims:  We have developed a novel tumor‐ablation device for liver tumors utilizing heat energy induced by magnesium ferrite (MgFe2O4) particles under an alternating magnetic field (AMF) produced by electric currents. This novel device can repeatedly heat liver tumors at lower temperature than usual heating devices, such as radiofrequency ablation therapy, with slight infliction of pain. This study assesses its heating effect on rat liver tumors as local therapy.

Multiendoscope-assisted treatment for blue rubber bleb nevus syndrome

Blue rubber bleb nevus syndrome is characterized by gastrointestinal and cutaneous hemangiomas and gastrointestinal bleeding causing anemia. We report a unique case of this syndrome in an adult woman. It was associated with congenital heart disease, for which the patient underwent surgery at 12 months of age, and cutaneous hemangiomas, for which surgery was performed later in childhood. Gastrointestinal bleeding was diagnosed and treated when she was 21 years of age after a workup for iron deficiency anemia. Successful total resection of all gastrointestinal hemangiomas was performed by minimally invasive surgery with gastric, small intestinal, and colonic fiberscopy and laparoscopy. The postoperative course was uneventful. The patient could walk the day after surgery, and she was discharged from the hospital 14 days after surgery. Our experience and findings given in other reports suggest that total resection of hemangiomas should be the final goal and that minimal skin incision is preferable for this benign disease, with multiendoscope-assisted treatment to ensure that any hemangiomas remaining in the gastrointestinal tract are not overlooked.

True Carcinosarcoma of the Esophagus: Report of a Case

Carcinosarcoma of the esophagus is a malignant neoplasm involving both carcinomatous and sarcomatous components. We report a patient with true esophageal carcinosarcoma who underwent laparoscopy-assisted surgery. An upper gastrointestinal barium study revealed a lobulated intraluminal filling defect in the lower intrathoracic esophagus. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. The esophageal hiatus was entered and the mediastinal esophagus was dissected using a laparoscopic approach. Microscopically, the tumor comprised poorly differentiated squamous cell carcinoma and spindle-shaped cells resembling leiomyosarcoma. Immunohistochemically, spindle-shaped sarcomatous cells displayed strongly positive reaction to vimentin and negative reaction to cytokeratin AE1/AE3 and CD68. No transitional zone was seen between sarcomatous and carcinomatous elements. The patient was finally diagnosed with true esophageal carcinosarcoma. Laparoscopic transhiatal esophagectomy seems to be a rational and safe procedure for lower esophageal neoplasms, even for patients with impaired respiratory function.

Postcardiac injury syndrome following vascular interventional radiofrequency ablation for paroxysmal atrial fibrillation

Postcardiac injury syndrome (PCIS) occurs following a pericardial or myocardial injury. On the other hand, PCIS following cardiac catheter intervention is rare and can be difficult to diagnose because of its delayed onset. A 24-year-old man underwent radiofrequency ablation (RFA) for paroxysmal atrial fibrillation and suffered from general fatigue and left-sided pleural effusion three months after the procedure. His symptoms and effusion were effectively treated within a month by administrating nonsteroidal anti-inflammatory drugs. However, seven months later, he developed left-sided chest pain and low-grade fever. Computed tomography showed a thickening of the parietal pleura and reccurence of the pleural effusion. Pleural biopsy by video-assisted thoracoscopy demonstrated chronic pleuritis with a non-necrotizing granulomatous reaction. Given the previous RFA, and in the absence of infection or malignant disease, he was diagnosed with PCIS and treated with colchicine.

A case report of tuberculous abscess of the chest wall accompanied with pulmonary carcinoma

With the decreasing incidence of tuberculosis (TB), tuberculous abscess of the chest wall (TACW) is becoming rare. Pulmonary carcinoma coexisting with pulmonary TB has been reported in the past, but reports of pulmonary TB accompanied with TACW are scarce. We present the first case of a 66-year-old male with TACW accompanied with pulmonary carcinoma.

Hoarseness after radical surgery with systematic lymph node dissection for primary lung cancer

OBJECTIVES Radical surgery with systematic upper mediastinal node dissection for primary lung cancer can cause recurrent laryngeal nerve (RLN) paralysis, but this is poorly reported. METHODS We retrospectively reviewed the clinical data for consecutive patients who underwent radical surgery for primary lung cancer with an observation period of at least 12 months. During follow-up, hoarseness and vocal fold movement were assessed clinically and laryngoscopically, respectively. RESULTS Of the 365 patients included in this study, 22 (6.0%) experienced hoarseness as a complication. All 22 patients who experienced hoarseness had undergone upper mediastinal node dissection. Although 1 of the 22 patients refused to undergo laryngoscopy, we assessed the vocal fold movement in the remaining patients (95.5%). Among these, 5 patients (23.8%) had right RLN paralysis, and 15 (71.4%) had left RLN paralysis and showed no sign of RLN paralysis. Over 1-24 months, vocal cord movement improved in 61.1% (11/18); and over 1-28 months, hoarseness improved in 72.7% (16/22). All patients with right RLN paralysis improved without further treatment. CONCLUSIONS We conclude that extensive follow-up is necessary to discern whether hoarseness is a temporary or permanent complication of radical surgery in patients with primary lung cancer who have undergone systematic lymph node dissection.

Thoracic Empyema Caused by Percutaneous Transhepatic Gallbladder Drainage

Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative to emergency laparoscopic cholecystectomy in high-risk patients with acute cholecystitis. Severe complications of this procedure are rare, except for drainage tube-related complications. A case of thoracic empyema, which is a rare complication of PTGBD, is reported; penetration of the pleural cavity seemed to be the cause of the thoracic empyema.