[show abstract][hide abstract] ABSTRACT: Fatty acid synthase is highly expressed in many types of human cancers. Cerulenin, a natural inhibitor of fatty acid synthase, induced apoptosis in the human colon cancer cell lines HCT116 and RKO. Oxaliplatin also induced cell death in these cell lines. Cerulenin treatment was associated with reduced levels of phosphorylated Akt, activation of p38 and induced caspase-3 cleavage and finally caused apoptosis. Oxaliplatin induced activation of the p53-p21 pathway and p38. In combination with cerulenin and oxaliplatin, activation of the p53-p21 pathway and p38 occurred in a smaller concentration and finally induced caspase-3 cleavage in a smaller concentration of cerulenin and oxaliplatin. In xenotransplanted SCID mice, the cerulenin + oxaliplatin group significantly inhibited tumor progression compared to the control, cerulenin and oxaliplatin groups. Based on these studies, inhibiting fatty acid synthase would be an effective strategy to treat unresectable colorectal cancer tumors in combination with oxaliplatin. Fatty acid synthase inhibitor would be one of the best counterparts of oxaliplatin, which reduces the dose and side-effects of oxaliplatin and would make it possible to endure the chemotherapy over a longer period.
International Journal of Oncology 06/2013; · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the efficacy and safety of neoadjuvant chemotherapy using modified OPTIMOX1 plus bevacizumab for advanced rectal cancer.
Nine cases with highly advanced rectal cancer for which curative surgery was potentially difficult were enrolled(clinical T4 in 7 cases, lateral node metastasis in 3 cases, M1 in 2 cases).
The number of courses of modified OPTIMOX1(mFOLFOX6 and sLV5FU2, alternating administration)plus bevacizumab ranged from 1 to 21(median: 10). Surgical procedures consisted of internal sphincter resection(ISR)in 4 patients, ultra-low anterior resection(ULAR)in 2 patients, pelvic exenteration(TPE)in 2 patients, and Hartmann's procedure in 1 patient. Liver resection was conducted in 2 patients. RM1 was confirmed in 2 patients, but curative surgery was performed in the other patients. Histological efficacy of grade x/1a/1b/2were seen in the above 1/4/2/2 cases, respectively. Neurotoxicity associated with oxaliplatin was mild; no grade 3 neurotoxicity was noted. Recurrence has been confirmed in 5 patients at the median follow-up period of 650 days.
It was suggested that modified OPTIMOX1 plus bevacizumab is effective and safe to administer as a neoadjuvant chemotherapy for curative resection or anus-preserving surgery in patients with highly advanced rectal cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2012; 39(7):1087-91.
[show abstract][hide abstract] ABSTRACT: We applied a new concept of "image overlay surgery" consisting of the integration of virtual reality (VR) and augmented reality (AR) technology, in which dynamic 3D images were superimposed on the patient's actual body surface and evaluated as a reference for surgical navigation in gastrointestinal, hepatobiliary and pancreatic surgery.
We carried out seven surgeries, including three cholecystectomies, two gastrectomies and two colectomies. A Macintosh and a DICOM workstation OsiriX were used in the operating room for image analysis. Raw data of the preoperative patient information obtained via MDCT were reconstructed to volume rendering and projected onto the patient's body surface during the surgeries. For accurate registration, OsiriX was first set to reproduce the patient body surface, and the positional coordinates of the umbilicus, left and right nipples, and the inguinal region were fixed as physiological markers on the body surface to reduce the positional error.
The registration process was non-invasive and markerlesss, and was completed within 5 min. Image overlay navigation was helpful for 3D anatomical understanding of the surgical target in the gastrointestinal, hepatobiliary and pancreatic anatomies. The surgeon was able to minimize movement of the gaze and could utilize the image assistance without interfering with the forceps operation, reducing the gap from the VR. Unexpected organ injury could be avoided in all procedures. In biliary surgery, the projected virtual cholangiogram on the abdominal wall could advance safely with identification of the bile duct. For early gastric and colorectal cancer, the small tumors and blood vessels, which usually could not be found on the gastric serosa by laparoscopic view, were simultaneously detected on the body surface by carbon dioxide-enhanced MDCT. This provided accurate reconstructions of the tumor and involved lymph node, directly linked with optimization of the surgical procedures.
Our non-invasive markerless registration using physiological markers on the body surface reduced logistical efforts. The image overlay technique is a useful tool when highlighting hidden structures, giving more information.
Journal of hepato-biliary-pancreatic sciences. 10/2009; 17(5):629-36.
[show abstract][hide abstract] ABSTRACT: We investigated the feasibility of new carbon dioxide-enhanced virtual multidetector computed tomography (MDCT) cholangiopancreatography (CMCP) for intraluminal exploration in 73 patients with hepatobiliary and pancreatic disease.
CMCP was performed via a percutaneous or transpapillary drainage tube, and, synchronously, intravenous contrast material was employed for virtual angiography; three-dimensional (3D) virtual reality was incorporated using OsiriX and Fovia applications. The capability of carbon dioxide to delineate the biliary and pancreatic system was evaluated.
All CMCPs showed complete technical success; complications including pancreatitis or pain never occurred. The incidences of visible third- and fourth-order biliary branches were 100 and 86.0%. The capability of carbon dioxide to pass an obstruction through an occluded hilar bile duct malignancy was 80.0%; it provided feasible information on additional bile duct segments. The full extent of the gallbladder was depicted in 72.7% of the studies. Minimum 2-mm lesions of biliary stones or gallbladder polyps were clearly detected. The main or second-order pancreatic ducts were visible in 100 and 83.3% of the studies, respectively. Carbon dioxide enabled the replacement of mucin and pancreatic juice and facilitated the detection of cystic lesions of intraductal papillary-mucinous neoplasm (IPMN) in 75.0% of the studies. We succeeded in achieving 3D spatial recognition of vascular structures in the cholangiopancreatic region, through the fusion of CMCP and 3DCT arteriography and venography in a single image scanning, and radiation time was decreased. This combined modality proved to be feasible for planning operations and for image-guided navigated surgery in the resection of a malignancy.
To our knowledge, this is the first report to demonstrate the diagnostic accuracy of carbon dioxide MDCT cholangiopancreatography and the use of this modality for depicting biliary, pancreatic, and fusion blood vessels simultaneously. Carbon dioxide possesses many advantages over conventional iodinated contrast agents, and it might replace more invasive diagnostic measures in the near future.
Journal of hepato-biliary-pancreatic sciences. 10/2009; 17(5):601-10.
[show abstract][hide abstract] ABSTRACT: Transgastric access is a major route in natural orifice translumenal endoscopic surgery (NOTES); gastrotomy should be performed unless it would damage surrounding organs in the peritoneal cavity. This article describes a novel rendezvous gastrotomy technique over a direct percutaneous endoscopic gastrostomy (PEG).
In six live porcines, the gastrotomy involved applying a direct PEG through the abdominal wall into the stomach and exchanging to a needle trocar. An endoscopic balloon catheter was passed through the trocar by rendezvous technique. Then the inflated balloon and endoscope were advanced to the peritoneal cavity through the gastrotomy. Transgastric cholecystectomy was performed with a hybrid needle grasper through the same percutaneous site and the gastrotomy was closed with endoscopic clips.
The rendezvous gastrotomy technique could reduce guidewire exchange. The success rate was 100% (6/6). Mean times for transgastric peritoneoscopy and cholecystectomy were 25.5 and 83.5 min. Mortality and morbidity was 0%. The addition of the extra trocar was unnecessary in all procedures.
The advantage of this introduction system includes the creation of controlled gastric perforation, which is easier to close. It provides reliable transgastric access and increases safety. It simplifies transgastric NOTES and provides less invasive hybrid NOTES procedure.
Journal of Hepato-Biliary-Pancreatic Surgery 08/2009; 16(6):758-62. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Natural orifice translumenal endoscopic surgery (NOTES) is a novel concept using an endoscope via a translumenal access for abdominal surgery. This study was designed to evaluate the feasibility and technical aspects of NOTES cholecystectomy from our experience on humans and animals.
NOTES cholecystectomies were performed in 12 animal experiments, including 8 pigs (6 by transgastric and 2 by transvaginal accesses) and 4 dogs (4 transvaginal accesses), and a human female cadaver.
The entire gallbladder could be removed under direct vision in all experiments. The average time was 60 min by transgastric and 40 min by transvaginal in animals. It was 87 min for human transvaginal cholecystectomy. In all animal and human procedures, there was no major complication concerning the operation.
The transvaginal route may be the easiest route for abdominal NOTES. Percutaneous endoscopic gastrostomy (PEG) allowed the safe performance of a controlled gastric perforation and shortened the time. The hybrid method allowed performance of a safe procedure and shortened the time.
Transvaginal and transgastric NOTES cholecystectomy is technically feasible and safe in both humans and animals. New instrumentation needs to be developed to perform a pure NOTES cholecystectomy without transabdominal assistance.
Journal of Hepato-Biliary-Pancreatic Surgery 05/2009; 16(3):255-60. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to examine correlations between pressure profile of the anal canal and postoperative defecatory disorder after sphincter-preserving operation (SPO) for rectal cancer.
Using three-dimensional vector manometry, pressure profile and length of the anal canal were evaluated more than 1 year after SPO according to operation method and degree of postoperative defecatory function in 53 patients with rectal cancer.
Compared with high anterior resection as a control, the anal canal was shorter in operations with a pelvic floor maneuver, namely, low anterior resection, ultra-low anterior resection, and intersphincteric resection. Patients with postoperative defecatory disorder showed significantly shorter anal canal length than patients with fair function. Length of the circular high-pressure zone (> or = 20 mmHg) < 20 mm in the resting state was a strong predictor of severe postoperative defecatory malfunction, with Wexner score> or =10.
Operative maneuvers at the pelvic floor during SPO for rectal cancer may damage anal sphincter or levator ani muscles. The circular high-pressure zone can be measured only by three-dimensional manometry and may offer a useful indicator of sphincter damage after SPO for rectal cancer.
Journal of the American College of Surgeons 04/2009; 208(3):362-7. · 4.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report a rare case of breast cancer with cartilaginous and/or osseous metaplasia. A 59-year-old woman had a large lump in her left breast, which had enlarged gradually over a period of 2 years. Mammography, ultrasonography and aspiration cytology suggested phyllodes tumor with carcinoma. She underwent wide excision and sentinel lymph node biopsy. Because of the existence metastatic tumor cells in the sentinel lymph node on frozen section, sequential axillary lymph node dissection was conducted consequently. Histologically, the tumor consisted of invasive ductal carcinoma and spindle-cell carcinoma, including cartilaginous metaplasia. Adjuvant chemotherapy and whole-breast irradiation were performed. However, she died of multiple metastases to the liver 2 years after surgery. Breast cancer with cartilaginous and/or osseous metaplasia belongs to a special type of invasive carcinoma, and the incidence is very low. We here present our case and a review of the literature.
Breast Cancer 02/2009; 16(3):234-7. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: After low anterior resection for rectal cancer, approximately 50% of patients experience defecatory malfunction such as multiple evacuations, urgency, and soiling. Since the neorectum is constructed with the remaining colonic segment, it can only substitute for the rectum to a limited extent. A straight anastomosis is most frequently used when the rectal remnant is sufficient, such as in high anterior resection. When the height of anastomosis is close to the anal sphincter, a J-pouch, a side-to-end, or a transverse coloplasty pouch are constructed to achieve better postoperative bowel function. The advantage of J-pouch reconstruction is not only the increased volume but also may be decreased motility when compared with straight reconstruction. In terms of postoperative function, the side-to-end and transverse coloplasty pouch have both been reported to exhibit similar functional results to J-pouch reconstruction. To obtain optimal functional results, pouch reconstruction should be considered, especially when the height of anastomosis is at the levator plane.
[show abstract][hide abstract] ABSTRACT: The preoperative image diagnosis in the biliary disease devolved from analog imaging such as PTCD or ERCP to digital data analysis such as MDCT, MRI, DIC-CT, or MRCP. In late years synchronous visualization of the biliary tracts and associated blood vessels was enabled in fusion method or MRCPA. Carbon dioxide enhanced MDCT cholangiopancreatography depicts the biliary and pancreatic duct by the negative contrasting effect of the carbon dioxide, and is ideal for the surgical navigation. Real time correspondence to the operator's demand is important, and multidirectional observation and volume rendering method are effective for the use of it during surgery. The introduction of image analysis software OsiriX improves complexity and image construction time, and it may be practical. Image overlay surgery consisted of augmented reality and mixed reality is developing toward practical use in navigated surgery. In recent years, NOTES (Natural Orifice Translumenal Endoscopic Surgery) was developed, the support system of the navigation of such flexible endoscope is desired earnestly.
[show abstract][hide abstract] ABSTRACT: Less invasive pancreatic head resection, such as duodenum-preserving pancreatic head resection (DPPHR) has been introduced for the treatment of pancreatoduodenal lesions, especially for benign conditions, for reducing surgical stress and maintaining exocrine and endocrine function of the residual pancreas in consideration of postoperative quality of life (QOL).
We investigated the feasibility of a new technique employing three-dimensional (3D) virtual pancreatography using multi-detector CT (MDCT) with carbon dioxide (CO2) gas as a negative contrast agent for detection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas requiring minimally invasive surgery. Branch IPMN is subjected in this study.
Contrast-enhanced MDCT scan of the abdomen diagnosed 4- to 20-mm multilocular septated cysts in the head-uncinate process of the pancreas. Endoscopic retrograde pancreatography (ERP) showed multiple cystic lesions in the head-uncinate process with mild dilatation in the remaining pancreatic duct. For localizing diagnosis of these small and multiple pancreatic cysts, we placed an endoscopic pancreatic stent (EPS), and MDCT with injection of CO2 via EPS was examined for the virtual CO2 pancreatography, consisting of OsiriX software system employing 3D virtual anatomic reconstruction with CO2 gas as a negative contrast agent. Virtual CO2 MDCT pancreatography demonstrated that all cystic lesions of the pancreas were contained within the area of the head-uncinate process of the pancreas. We performed DPPHR, and surgical margin of the patient's remnant pancreas was determined as non-malignant by intraoperative histology. There was no residual pancreatic cyst and tumor after surgery. The resected tumor was diagnosed as branch duct type intraductal papillary mucinous adenocarcinoma. According to our minimally invasive DPPHR obtained by virtual CO2 pancreatography, the pancreatic endocrine and exocrine functions of this patient were maintained at almost the same levels as those in his preoperative status. With respect to preservation of the endocrine and exocrine functions of the pancreas, DPPHR is a highly effective surgical procedure due to limited surgical resection.
Our new technique of virtual CO2 MDCT pancreatography is a feasible procedure for preservation of the remnant pancreatic function. This is the first report of virtual CO2 pancreatography providing minimally invasive pancreatic surgery.
[show abstract][hide abstract] ABSTRACT: Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.
[show abstract][hide abstract] ABSTRACT: Adenoid cystic carcinoma (ACC) of the breast is a rare variant of breast malignancy and is known to have an excellent prognosis. We report two cases of ACC diagnosed by preoperative fine-needle aspiration cytology (FNAC), which proved to be very useful in determining the appropriate treatment. The patients were a 57-year-old woman (case 1) and a 71-year-old woman (case 2). On physical examinations and imaging studies both tumors were recognized as lobulated tumors that measured 3.0 x 2.3 cm (case 1) and 3.9 x 3.4 cm (case 2) respectively. FNAC materials showed clusters of malignant cells surrounding globules of mucus, therefore, ACC was diagnosed. Considering the characteristics of ACC, breast-conserving surgeries with axillary dissection and adjuvant radiotherapy were performed instead of primary chemotherapy or mastectomy. Histologically, a distinctive biphasic pattern was observed that consisted of true laminae and pseudocystic spaces. Tumor sizes were 4.0 x 3.3 cm (case 1) and 4.6 x 3.8 cm (case 2), respectively, and surgical margins were negative on microscopic examination. Lymph node metastasis was not present in either case. Even though ACC is very rare, preoperative diagnosis can be made based on its characteristic features. Preoperative diagnosis is extremely useful for determining appropriate treatment.
Breast Cancer 02/2006; 13(1):112-6. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Breast carcinoma is usually accompanied by an invasive component with an intraductal component, and each component shows different morphological features. We evaluated whether the presence or absence of comedonecrosis is correlated with prognosis and biological features in node-negative invasive breast carcinoma. Ninety-four node-negative breast carcinomas with an intraductal component were classified into two types: comedo type (n = 36) showing comedonecrosis partly or extensively in the intraductal component, and non-comedo type (n = 58) showing either an absence or small foci of necrosis. The Kaplan-Meier method was used to calculate disease-free survival. Immunohistochemical examination for p53 and HER-2 was conducted on the comedo (n = 35) and non-comedo (n = 47) type tumor specimens. Disease-free survival was significantly shorter in the comedo type than in the non-comedo type (P = 0.019). The expression of p53 was observed in 16 (45.7%) of the 35 comedo type cases, but only in two (4.3%) of the 47 non-comedo type cases (P < 0.0001). HER-2 overexpression was observed in seven (20.0%) of the 35 comedo type cases, while none of the 47 non-comedo type cases overexpressed HER-2 (P < 0.0001). These results suggest that the presence of comedonecrosis may be predictive of an unfavorable prognosis with aggressive biological behavior in node-negative invasive breast carcinoma.
Pathology International 08/2003; 53(8):501-6. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined a 31-year-old woman with a solid mass in her left axilla. Physical examination and ultrasonography confirmed a 2 cm well-defined mass. Fine needle aspiration biopsy suggested fibroadenoma of breast. Excisional biopsy revealed benign phyllodes tumor of the ectopic breast tissue. Phyllodes tumor in ectopic breast tissue is an extremely rare occurrence. Only nine cases have been reported, including tumors of the vulva, inguinal region and axilla. This is the second case in the axillary region.
Breast Cancer 02/2003; 10(1):82-4. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: To clarify the usefulness of imprint cytology for intraoperative investigations of sentinel lymph nodes in breast cancer, comparing the results with those of examinations using frozen and permanent sections.
The material consisted of 303 sentinel lymph nodes from 124 cases of clinically node negative breast cancer. Touch imprint cytologic slides and frozen sections were obtained from the same cut surface of the sentinel nodes. Correlations with the final histopathologic results in paraffin sections were evaluated.
The sensitivity, specificity and accuracy of imprint cytology were 70.3%, 99.6% and 96.0%, and those of frozen sections were 83.8%, 100%, 98.0%, respectively. The values were improved when the 2 methods were combined (89.2%, 99.6%, 98.3%), though the concordance between imprint cytology and frozen section was 91.9%.
Both imprint cytology and frozen section are useful for evaluating sentinel lymph node status in breast cancer. However, the 2 techniques should be combined to improve the diagnostic sensitivity.
[show abstract][hide abstract] ABSTRACT: Using computerized nuclear morphometry, we searched for common, objective parameters for use in predicting potential malignancy of primary T2 tumors of the rectum.
In 119 surgically resected T2 rectal cancers, the following parameters of the cancer cell nuclei were microscopically measured: mean nuclear area (NA), mean perimeter (PM), largest-to-smallest diameter ratios (LS), circularity factor (CF), and coefficient of variation of nuclear area (NACV). The calculated parameters were retrospectively analyzed and compared with patients' outcome.
NA, PM, and NACV correlated with recurrence. NA and NACV were significantly associated with disease-free survival. High NACV correlated with lymph node metastasis. In node-negative cases, high NACV correlated with recurrence and tended to be associated with poor prognosis.
These findings suggest that computerized morphometry is useful for predicting malignancy potential of T2 lesions of the rectum.
The American Journal of Surgery 07/2002; 183(6):686-91. · 2.52 Impact Factor