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ABSTRACT: BACKGROUND: Indications for laparoscopic gastrectomy (LG) for early stomach cancer have spread worldwide and evaluation of short-term outcomes has been favorable. The present study aimed to evaluate both technical feasibility and safety of LG and short-and long-term outcomes after LG. METHODS: The study group comprised 231 patients who underwent LG during the period from August 2001 through December 2011 at Gifu University School of Medicine. RESULTS: Concomitant resection of other organs was performed in 16 (6.9 %) of the 231 patients, and conversion to open surgery was performed in 5 (2.2 %) patients. The final clinical stage of the patients, according to the Union for International Cancer Control classification, was stage IA in 183 (79.0 %), stage IB in 26 (11.3 %), stage IIA in 9 (2.6 %), stage IIB in 6 (2.6 %), stage IIIA in 5 (2.2 %), and stage IIIB in 2 (0.9 %) patients. Average values of total blood loss and operation time were 133.7 ± 129.0 ml and 328.1 ± 70.1 min, respectively. Postoperative complications were detected in 29 patients (12.6 %), and one patient died. According to the Clavien-Dindo classification of surgical complications, the rate of severe complications of grade ≥3a was 6.1 % and that of grade ≥3b was 1.3 %. There were no significant differences in complications in relation to clinicopathological or operative procedures. Cancer recurrence was detected in 2 (0.9 %) patients. In the patient with peritoneal dissemination, tumor size and macroscopic type were critical. Five-year overall survival rates were 99.3 % for stage IA, 95.2 % for stage IB, and 50.0 % for stage IIB patients. One recurrence each was detected for stages IA and IIB cancers. CONCLUSION: The present study showed LG to have a safe postoperative course and to benefit oncologic outcomes.
Surgical Endoscopy 03/2013; · 4.01 Impact Factor
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Chiaki Yoshimi,
Maya Yamada,
Hironori Fujii,
Minako Nishigaki,
Hirotoshi Iihara,
Kiyoyuki Kitaichi,
Mayu Takahashi,
Sayoko Kurahashi, Takao Takahashi,
Kazuhiro Yoshida,
Yoshinori Itoh
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ABSTRACT: In the outpatient cancer chemotherapy clinic of Gifu University Hospital, pharmacists contributed to the provision of safe and efficacious cancer chemotherapy as full-time staff, together with doctors, nurses and other medical staff. Since April 2010, three pharmacists have been in charge of the provision of pharmaceutical care services(PCS)to all patients. Furthermore, pharmaceutical intervention before medical examination(pre-PCS)was initiated in May 2011. As a consequence, the time spent for patient education and monitoring significantly(p<0. 001)increased from 39. 7±3. 2min/patient in 2010 to 48. 0±2. 6min/patient in 2011. The number of proposals on prescriptions also significantly increased, 2. 5 times, compared to 2010. The percentage of the acceptance of proposals was 94% in fiscal year 2011. Importantly, pre-PCS improved the control of chemotherapy-induced nausea and vomiting, peripheral neuropathy and skin rash. These results suggest that pre-PCS by pharmacists would be beneficial to progress the quality of outpatient cancer chemotherapy.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2013; 40(3):349-354.
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Nippon rinsho. Japanese journal of clinical medicine 09/2012; 70 Suppl 7:354-9.
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ABSTRACT: We characterized molecular mechanisms of vitamin K3 (VK3)-induced inhibition of proliferation to evaluate VK3 effectiveness
in treating advanced pancreatic cancer. A novel endoscopic drug delivery system, ultrasound injection technique, was used
to study local effects of VK3. VK3 inhibited pancreas cancer cell growth by rapid phosphorylation of growth factor receptor
and cellular signal factors such as extracellular signal-regulated kinase. VK3 also activated apoptosis, and apoptosis inhibitor
antagonized the apoptosis pathway without inhibiting cell growth. Thiol antioxidant treatment completely abrogated VK3-induced
ERK but not JNK phosphorylation or inhibition of proliferation. Non-thiol antioxidant did not affect ERK phosphorylation or
growth inhibitory actions. Arylation was considered the main mechanism of VK3-induced growth inhibition through ERK activation.
VK3 may lead to favorable outcomes in the treatment of pancreatic tumors. Detection of ERK phosphorylation in tissue is important
to predict VK3 effect. Endoscopic ultrasound-guided fine-needle injection may be beneficial for treating pancreatic cancer
with VK3.
KeywordsVitamin K3–Pancreas cancer–EUS-guided FNI–Signal transduction–ERK
Oncology Reviews 04/2012; 5(1):57-60.
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ABSTRACT: Because the aging process varies among individuals, elderly people of the same age, especially those over 80 years, do not necessarily have similar organ function. After consideration of lower organ function and concomitant disease, less invasive treatment should be selected for elderly patients. Therefore, it is important to limit preventive lymph node dissection, and when determining the dose of anticancer drugs, major organ function should be taken into consideration.
Nippon Geka Gakkai zasshi 01/2012; 113(1):26-30.
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ABSTRACT: More effective regimens are urgently needed for treatment of esophageal carcinoma; therefore, we conducted a phase I trial of a combination of docetaxel, nedaplatin, and S-1 (DGS) to determine the optimal dose in patients with advanced esophageal carcinoma.
We studied 14 patients with previously untreated advanced cervical esophageal carcinoma with T3-4 tumors and/or M1 staging and esophageal carcinoma with cervical lymph node metastasis. The patients received an infusion of docetaxel at different dose levels (levels 1, 2, 3, 4: 25, 30, 35, 40 mg/m(2), respectively) and an infusion of nedaplatin (40 mg/m(2)) on day 8 plus oral administration of S1 (80 mg/m(2)/day) for two consecutive weeks at two-week intervals.
Dose-limiting toxicities (DLTs) included febrile neutropenia and leukopenia. DLTs occurred in 2 out of 5 patients at level 4. The response rate was 78.6 (11/14)%, including a complete response rate of 35.7(5/14)%.
The DGS regimen reported here was well tolerated and toxicities were manageable. The maximum tolerated dose was level 4, and the recommended dose was determined to be docetaxel at 35 mg/m(2) with nedaplatin at 40 mg/m(2) plus S1 at 80 mg/m(2). We found that our regimen, administered on an outpatient basis, showed high activity and tolerance. A phase II study has been started.
Anticancer research 12/2011; 31(12):4589-97. · 1.73 Impact Factor
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Hisashi Imai,
Shinji Osada,
Yoshiyuki Sasaki,
Aiko Ikawa,
Yoshihiro Tanaka,
Naoki Okumura,
Kenichi Nonaka, Takao Takahashi,
Kazuya Yamaguchi,
Kazuhiro Yoshida,
Masanori Nakashima,
Yoshinobu Hirose
Pancreas 07/2011; 40(5):795-6. · 2.39 Impact Factor
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ABSTRACT: The 9th International Conference of the Asia Clinical Oncology Society(ACOS)was held at Gifu Grand Hotel, Gifu Japan on August 25, 26, and 27 2010. The Society was established in Osaka, Japan, in October 1991. Meeting have been held every two years, starting in Osaka, and then to Bangkok, Kunming, Bali, Taipei, Seoul, Beijing, Manila, and now to Gifu. There was a twenty year interval in Japan between meetings in Osaka and Gifu. The main theme of the 9th ACOS was titled "Talk to the Worldwide from Asia," and the sub-theme was titled "Multidisciplinary Treatment for Asian Cancer Patients "For this 9th ACOS, we gathered 42 councilors from Asian countries to serve on the ACOS committee and 365 doctors from Japan to serve on a local organizing committee. For congress program, we scheduled 161 special sessions for the president's lectures, key note lectures, special lectures, educational lectures, symposium, workshop, luncheon seminars, etc. We received about 500 abstracts for oral or poster presentations; among them, 140 abstracts came from Asian countries. As for speakers, 475 were from Japan, 85 from Korea, 34 from Taiwan, 27 from China, over 10 from India, Indonesia, Viet Nam, USA, and other countries. Finally a total of 704 speakers were gathered from 20 countries(from the outside Asia; UK, France, Germany, and Australia). The total number of registered investigators was 1, 136, and the total number of participants, including our congress staffs, volunteers, neighborhood doctors, Gifu citizens, patients, etc., was over 1, 500. In this 9th ACOS we discussed some new ideas, such as Asian cancer statistics, mission, vision and core values of ACOS, new anti-cancer drugs developed from Japan(TS-1 and Xeloda), Inter group clinical trials among Asian countries, less invasive surgery using endoscopic assisted operation, Asian traditional medicine, open workshops with citizens, etc. Moreover, we published a commemorative book entitled" Recent Advances of Cancer in Asian Countries.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2011; 38(6):885-91.
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ABSTRACT: Mucinous cystic neoplasms (MCNs) make up a morphologic family of similar appearing tumors arising in the ovary and various extraovarian organs such as pancreas, hepatobiliary tract and mesentery. MCNs of the pancreas occur almost exclusively in women. Here, we report a rare case of MCN in a male patient. A 39-year-old man was admitted to our hospital with the chief complaint of back pain. Abdominal computed tomography revealed a multilocular cyctic mass 6.3 cm in diameter in the pancreatic tail. In addition, the outer wall and septae with calcification were demonstrated in the cystic lesion. On magnetic resonance imaging , the cystic fluid had low intensity on T1-weighted imaging and high intensity on T2-weighted imaging. Endoscopic retrograde cholangio-pancreatography (ERCP) showed neither communication between the cystic lesion and the main pancreatic duct nor encasement of the main pancreatic duct. Endoscopic ultrasonography revealed neither solid component nor thickness of the septae in the cystic lesion. Consequently, we performed distal pancreatectomy with splenectomy under the diagnosis of cystic neoplasia of the pancreas. Histopathologically, the cystic lesion showed two distinct component: an inner epithelial layer and an outer densely cellular ovarian-type stromal layer. Based on these findings, the cystic lesion was diagnosed as MCN.
Rare tumors 04/2011; 3(2):e14.
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The American surgeon 03/2011; 77(3):E57-8. · 1.28 Impact Factor
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ABSTRACT: Outpatient cancer chemotherapy is increasing with the development of anticancer agents, and roles of medical staff are becoming more and more important in cancer chemotherapy. We showed here roles of pharmacists with experience in oncology and evaluated outcomes of their activities in medical practices in cancer chemotherapy clinic.
Two pharmacists were newly assigned to the outpatient cancer chemotherapy clinic, where they were in charge of verification of prescription orders, mixing of anticancer injections, monitoring adverse drug reactions, implementation of supportive care and provision of information about cancer chemotherapy to medical staff and patients. The number of patients, amounts of mixing of anticancer injections and hospital revenue were compared before and after assignment of pharmacists. Management of chemotherapy-induced nausea and vomiting in breast cancer patients receiving the combination chemotherapy with anthracycline and cyclophosphamide were also compared.
Pharmacists spent 75 hours per month in patient education and adverse drug reactions monitoring, which led to the reduction of the workload of physicians. As a consequence, the number of outpatients and the resultant hospital revenue markedly increased. In addition, facilitation of proper use of anti-emetic drugs led to the improved control of chemotherapy-induced nausea with reducing the cost for anti-emesis by 16%.
Pharmacists contributed to the improved efficiency of medical practices.
Journal of Evaluation in Clinical Practice 03/2011; 18(4):753-60. · 1.23 Impact Factor
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ABSTRACT: In the new era of technical development in surgery, operative devices, molecular targeting and chemotherapeutic agents, surgical oncologists have two main roles in the treatment of gastric cancer. One is to provide patients with minimally invasive surgery, including laparoscopy- or robot-assisted surgery in early gastric cancer patients, and the new concept of surgical intervention toward advanced and metastatic disease. Since recently, laparoscopy-assisted distal gastrectomy has become prevalent in Japan as a surgery which is minimally invasive for the patients and provides them with a good quality of life afterwards. However, the provision of advanced surgical techniques, including lymph node dissection and reconstruction, is more important for patient survival. The second role of surgical oncologists is to evaluate the significant values of the aggressive treatment which we term 'adjuvant surgery' for stage IV gastric cancer patients who have successfully responded to initial chemotherapy for curative intent. Stage IV gastric cancer patients are now being informed about the possibility of longer survival with the new chemotherapeutic and surgical strategic approach.
Pathobiology 01/2011; 78(6):343-52. · 1.18 Impact Factor
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ABSTRACT: The first aim was to determine whether hypermethylation of certain tumor related genes, including 3OST2, CHFR, RUNX3, and p16, could be detected in Japanese colorectal cancer (CRC) patients. The second was to utilize the most frequently hypermethylated genes as biomarkers for early detection of CRC.
We investigated the aberrant promoter methylation profile of 4 genes in 129 colorectal tumors and corresponding normal mucosa. For the second step, bowel lavage and blood of the main tumor drainage vein from 21 CRC patients were analyzed.
The 3OST2 gene was the most frequently methylated (57%) and was methylated frequently (9/21, 43%) in bowel lavage but rarely (1/21; 4.7%) in the venous drainage. The concordance between 3OST2 methylation in bowel lavage and corresponding tumor samples was 71.4%.
These results may show the possibility of early detection for CRC by examining 3OST2 gene methylation status in DNA extracted from stool.
Anticancer research 12/2010; 30(12):4811-8. · 1.73 Impact Factor
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ABSTRACT: Thymidylate synthase (TS) inhibitors activate human equilibrative nucleoside transporter 1. We evaluated the contribution of TS expression to determine a treatment method providing an effect from gemcitabine (GEM).
The expression of 5-fluorouracil (5-FU) and GEM metabolic factors (5-FU: TS, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase; GEM: human equilibrative nucleoside transporter 1, deoxycytidine kinase, cytidine deaminase, 5'-nucleotidase) were studied in 7 pancreatic cancer cell lines by Western blotting, and drug resistance was evaluated by 3-[4,5-dimethylthiazol]-2,5-dephenyl tetrazolium bromide assay. The expression of 5-FU factors was observed immunohistochemically in resected pancreatic cancer specimens.
Gemcitabine concentrations that inhibited colony formation by 50% correlated with TS protein expression (P = 0.0169). With a 5-FU non-growth-inhibiting dose, GEM concentrations that inhibited colony formation by 50% were significantly reduced by one fourth to one tenth. Knockout of TS expression by small interfering RNA decreased resistance to GEM in the cell lines (P = 0.0019). Immunohistochemically, TS expression related to disease-free survival time of patients treated with GEM (P = 0.0224). A high expression of 5-FU factors was detected: orotate phosphoribosyltransferase: differentiated cases (P = 0.0137), lower T factor (P = 0.0411); dihydropyrimidine dehydrogenase: nerve invasion (P = 0.0188), lymph node recurrence (P = 0.0253); TS, positive N factor (P = 0.0061).
The expression of TS provides an alternative source of substrate for DNA synthesis and positively correlates with GEM resistance and shortened patient survival.
Pancreas 11/2010; 39(8):1284-92. · 2.39 Impact Factor
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ABSTRACT: The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinoma.
We studied a total of 18 patients who had previously untreated thoracic esophageal squamous cell carcinoma with T4 tumors and/or metastasis. The patients received an infusion of docetaxel at different dose levels (levels 1, 2, 3: 30, 35, 40 mg/m(2), respectively) and an infusion of cisplatin (40 mg/m(2)) on days 1 and 15 plus a continuous infusion of 5-FU (400 mg/m(2)/day) on days 1-5 and 15-19.
Dose-limiting toxicities (DLT) included febrile neutropenia and leukopenia. DLT occurred in 2 of 6 patients at level 1, 2 and in 3 of 6 patients at level 3. The response rate was 88.9%, including a complete response rate of 33.3%.
To minimize toxicity and maximize dose intensity, we elected to investigate a biweekly regimen. The maximum tolerated dose was level 3, and the recommended dose was determined to be docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) plus 5-FU 400 mg/m(2), administered biweekly. This regimen was tolerable and highly active. A phase II study has been started.
Cancer Chemotherapy and Pharmacology 09/2010; 66(6):1159-65. · 2.83 Impact Factor
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ABSTRACT: Liver metastasis is one of the most critical factors in deciding the prognosis of patients with colorectal cancer (CRC). Hepatectomy is the most curative treatment for liver metastasis of CRC. The high amount of hepatocyte growth factor (HGF) is produced to promote liver regeneration by hepatectomy. Theoretically, HGF produced after hepatectomy stimulates the progression of CRC cells with c-Met in residual liver. This study was aimed to evaluate the value of hepatectomy towards liver metastasis of CRC in relation to the HGF/c-Met pathway. Ninety-four patients with CRC (including 24 liver metastasis cases) were operated at Gifu University Hospital (2002-2004). For these cases, the expression of c-Met in the primary and liver metastatic sites was evaluated by immunohistochemistry and Western blot. Experiments were also conducted on CT26 murine CRC cell line and a mouse liver metastasis model. In clinical study, the c-Met expression in liver metastatic sites was lower than in the primary sites in 87% of 24 cases. In basic study, the expression of c-Met protein in the liver tumor was significantly lower than in culture cells according to Western blot (p=0.033). The growth of residual liver tumors was not significantly different between 30% hepatectomy group and no operation group. The over-expression of c-Met was closely associated with CRC liver metastases. On the other hand, in liver metastatic lesions, the c-Met expression was reduced in comparison to primary lesions. Therefore, even if serum HGF levels increased due to liver resection during the regeneration period, residual liver metastases of CRC was not promoted in its progression. Aggressive hepatectomy would still be acceptable and favorable as a curative therapy.
International Journal of Oncology 08/2010; 37(2):289-97. · 2.40 Impact Factor
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ABSTRACT: To determine a novel chemotherapeutic concept for hormone receptor-negative and HER2-positive breast cancer, a high progression form of the disease for which treatment has been difficult. A combination therapy of 5-fluorouracil (5-FU) with rapamycin (Rap) was examined.
The growth inhibitory effect of treatment was evaluated by an MTT assay and cellular signal/apoptotic pathways were investigated by Western blotting and Hoechst 33342 staining.
Rap was shown to induce an inhibitory effect on the phosphorylation of mTOR and p70S6K. The expression of thymidine synthase (TS) was decreased by Rap. The addition of 5-FU to Rap was found to increase cell death. The Hoechst 33342 assay showed that apoptosis was increased by the combination of 5-FU and Rap in comparison to 5FU alone.
5-FU is more effective in combination with the TS-reducing action of Rap, even for highly HER2-expressing breast cancer cells.
Anticancer research 07/2010; 30(7):2625-30. · 1.73 Impact Factor
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ABSTRACT: A comparison was made between pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous carcinoma (IPMC) in order to understand the association between several markers and malignant potential.
Fifteen surgically resected PDACs and four IPMCs were subjected to immunohistochemistry with primary antibodies to Ki-67, p53, MUC2, Gli-1, and Claudin-18 (CLDN18).
Ki-67, P53, MUC2, Gli-1 and CLDN18 were positive in 6 (50%), 10 (66.6%), 0 (0%), 4 (26.6%), and 6 (40%) of the 15 PDACs, respectively. Low- to high-grade PanIN complexes were found in 2 out of the 15 PDACs. Gli-1 was continuously expressed in low- and high-grade PanINs. CLDN18 was specifically expressed in high-grade PanINs, whereas the corresponding invasive tubules did not express CLDN18. P53 was positively stained in one of the 4 IPMCs in which minimally invasive tubular type carcinomas were observed. Ki-67 and CLDN18 were positively stained in all 4 IPMCs. CLDN18 was specifically expressed in intestinal-type components of IPMCs.
CLDN18 is involved in intestinal-type epithelial differentiation in the progression of IPMCs, contradicting the previous knowledge of its specificity in gastric epithelial differentiation.
Anticancer research 07/2010; 30(7):2995-3003. · 1.73 Impact Factor
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The American surgeon 04/2010; 76(4):456-7. · 1.28 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the pattern of expression of c-Met and Ki67 in several components of biliary carcinoma. Fourteen surgically resected samples, including five intrahepatic cholangiocarcinomas, five gallbladder carcinomas, and four extrahepatic bile duct carcinomas, were subjected to immunohistochemistry with primary antibodies. In all 13 cases, intraductal neoplastic components showed diffuse staining for c-Met localized in the cell membrane, whereas 10 of the 14 cases lacked expression of c-Met in the corresponding invasive components. In four cases, invasive components composed of undifferentiated carcinoma (n = 2), signet-ring cell carcinoma (n = 1), and squamous cell carcinoma (n = 1) showed nuclear or perinuclear staining for c-Met. Conversely, 11 of the 13 cases did not express Ki67 in intraductal neoplastic components, whereas corresponding invasive components showed diffuse nuclear staining in all 14 cases. A comparison of the patterns of expression between c-Met and Ki67 at the boundary between intraductal and invasive components clearly demonstrated the complementary expression of c-Met and Ki67. Our results suggested that c-Met is involved in early events of carcinogenesis and Ki67 is involved in the formation of invasive carcinoma. However, exceptional cases were also observed, which might be associated with specificity for histologic subtypes and malignant potential.
The American surgeon 04/2010; 76(4):372-9. · 1.28 Impact Factor
