Weekly paclitaxel administration and intraabdominal CBDCA injection possibly beneficial treatment for recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation--a case report

A 46-year-old woman who had received mastectomy for breast cancer 6 years earlier complained of abdominal distension. Computed tomography and ultrasonography revealed massive ascites and ovarian swelling of both sides. She was diagnosed as having primary ovarian cancer and peritoneal dissemination, and underwent a total hysterectomy as well as ovarectomy on both sides. After surgery, she received a sequential chemotherapy, ie, intraabdominal injection of carboplatin (CBDCA 300 mg/m2) and div administration of paclitaxel (PTX 180 mg/m2) as a standard regimen for advanced ovarian cancer. However, detailed histological examinations showed that the ovarian cancer had metastasized from her breast cancer. It is well-known that breast cancer easily metastasizes to the bone, liver, pleura and lymph node, but rarely to the ovarium or peritoneum when chemotherapy is conducted. Therefore, no standard therapy has been established for breast cancer metastasizing to the ovarium. Our patient received 4 cycles of weekly administration of PTX (PTX 80 mg/m2, 3 consecutive weeks, 1-week break), followed by oral administration of doxifluridine+anastrozole on an outpatient basis. No evidence of recurrence of breast cancer has been noted 1 year after surgery. This result suggests that weekly administration of PTX and intraabdominal injection of CBDCA might be beneficial in the treatment of recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation.     

Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transduction into glioma cells in vitro.

PURPOSE: Recombinant adenoviral vectors are widely used in clinical and experimental studies to treat malignant tumors. Recently, host immune responses have been proposed as a major limitation in using adenoviral vectors for repeated gene delivery. We demonstrate another limitation unrelated to host immunity. EXPERIMENTAL DESIGN: We repeatedly transduced an adenoviral vector expressing the human p53 gene (AxCIhp53) into U373MG, a p53-susceptible cell line, and established the AxCIhp53-resistant cell line U373R. Most U373R cells survived even after AxCIhp53 treatment due to reduced transduction efficiency. Expression levels of adenovirus receptors were estimated to investigate the cause of reduced transduction efficiency. The mutant vector was used to overcome the resistance. RESULTS: The transduction efficiency of an adenoviral vector possessing the reporter LacZ gene (AxCAZ2-F/wt) for U373R cells was 25.4-fold less than that for parent cells. The expression levels of integrins alpha(v)beta(3) and alpha(v)beta(5) were found to be decreased in U373R cells without affecting the expression levels of Coxsackievirus and adenovirus receptor. The mutant vector AxCAZ2-F/K20, with a linker and a stretch of 20 lysine residues at the COOH-terminal of the fiber protein, improved the transduction efficiency of U373R cells to 12.6-fold of that of AxCAZ2-F/wt. A mutant vector carrying the p53 gene, AxCAhp53-F/K20, dramatically induced apoptosis in U373R cells. CONCLUSIONS: Glioma cells expressing low levels of adenovirus receptors might survive and proliferate to recur after repeated adenoviral transduction, even if the adenoviral transduction is effective at first. Changing the tropism of vectors is a potent method to overcome resistance.     

Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance

Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TEC contain stem cell‐like populations with high aldehyde dehydrogenase (ALDH) activity (ALDH^high TEC). ALDH^high TEC have proangiogenic properties compared with ALDH^low TEC. However, the association between ALDH^high TEC and drug resistance remains unclear. In the present study, we found that ALDH mRNA expression and activity were higher in both human and mouse TEC than in NEC. Human NEC:human microvascular endothelial cells (HMVEC) were treated with tumor‐conditioned medium (tumor CM). The ALDH^high population increased along with upregulation of stem‐related genes such as multidrug resistance 1, CD90, ALP, and Oct‐4. Tumor CM also induced sphere‐forming ability in HMVEC. Platelet‐derived growth factor (PDGF)‐A in tumor CM was shown to induce ALDH expression in HMVEC. Finally, ALDH^high TEC were resistant to fluorouracil (5‐FU) in vitro and in vivo. ALDH^high TEC showed a higher grade of aneuploidy compared with that in ALDH^low TEC. These results suggested that tumor‐secreting factor increases ALDH^high TEC populations that are resistant to 5‐FU. Therefore, ALDH^high TEC in tumor blood vessels might be an important target to overcome or prevent drug resistance.     

Comparison of advanced adenocarcinomas of esophagogastric junction and distal stomach in Japanese patients

Background

There have been no reports on the incidence, characteristics, treatment outcomes, and prognosis of inoperably advanced or recurrent adenocarcinoma of the esophagogastric junction (AEGJ) in Japan.

Methods

We investigated the clinicopathological characteristics, treatment outcomes, and prognosis for 816 patients with esophagogastric junctional and gastric adenocarcinoma who received first-line chemotherapy between 2004 and 2009.

Results

Of 816 patients, 82 (10 %) had AEGJ. The patients with AEGJ had significantly more lung and lymph node metastasis, but less peritoneal metastasis, than those with gastric adenocarcinoma (GAC). The objective response rate to first-line chemotherapy was 23.3 % for patients with AEGJ and 22.6 % in patients with GAC (p = 0.90). The median survival was 13.0 months in AEGJ and 11.8 months in GAC (p = 0.445). In no patient was tumor site a significant prognostic factor (p = 0.472). In patients with AEGJ, ECOG PS ≥ 2, presence of liver metastasis, and absence of lung metastasis were significantly associated with poor prognosis.

Conclusions

No significant differences were observed in treatment outcomes between advanced AEGJ and GAC. Therefore, the same chemotherapy regimen can be given as a treatment arm in future Japanese clinical trials to both patients with inoperably advanced or recurrent AEGJ and those with GAC.     

Cauda equina movement during the Valsalva maneuver in two patients with Lumbar spinal canal stenosis

Lumbar spinal canal stenosis (LSS) is a common spinal disorder among older people. Some LSS patients say that their pain worsens when they lift heavy objects. The Valsalva maneuver is the optimal breathing pattern for producing maximal force. Herein, we present two cases of LSS where the movement of the cauda equina was observed during the Valsalva maneuver.Case Summary: Case 1: A 74-year-old female with a history of LSS presented to our Department of Urology with frequent urination. The patient was diagnosed as having uterine and bladder prolapse. Pelvic cine MRI scan was conducted for detailed evaluation. While the Valsalva maneuver was performed to diagnose pelvic organ prolapses, we observed movement of the cauda equina. Spine MRI and CT, performed one year before presentation, showed severe LSS due to degenerative spondylolisthesis. Case 2: A 73-year-old male underwent radical prostatectomy for prostate cancer. A follow-up cine MRI to confirm urethrorrhea showed the cauda equina moving during the Valsalva maneuver. Moderate LSS due to degenerative spondylolisthesis was retrospectively found on abdominal CT performed before prostatectomy. Conclusion: The findings of our report suggest that movement of the cauda equina during the Valsalva maneuver may be implicated in LSS.     

Synovitis-acne-pustulosis-hyperostosis-osteitis Syndrome with Bilateral Pleural Effusion

Pleural effusion is a rare manifestation in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, which is characterized by the presence of osteoarticular lesions and dermatological involvement. We herein report a 71-year-old man with pleural effusion resulting from SAPHO syndrome. He was successfully treated using corticosteroids and has experienced no recurrence for one year. We should consider SAPHO syndrome when encountering cases of anterior chest pain and pleural fluid.     

Simple smoke ventilation method for uniportal video-assisted thoracoscopic surgery

Fogging of the thoracoscopic lens affects a surgeon’s ability to maintain a clear operating field. In uniportal video-assisted thoracoscopic surgery, the thoracoscopic lens tends to fog when the surgeon does not hold a suction instrument. Thus, a suction instrument needs to be held by the surgeon’s nondominant hand to remove surgical smoke, mist, and moisture. Here, we describe a simple, easy and cost-effective surgical smoke ventilation technique for uniportal video-assisted thoracoscopic surgery using a suction catheter to solve the problem. We present this technique and comment on its advantages, including decreased cost and improved surgical visualization.     

N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin

Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13?±?20.50 to 448.84?±?103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.