1.Diagnosis of pancreatic ductal carcinoma
Susumu Hijioka ; Kazuo Hara ; Nobumasa Mizuno ; Hiroshi Imaoka ; Kenji Yamao
Innovation 2014;8(4):100-101
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of gastrointestinal
cancer, with a 5-year survival rate of 5%; it remains a significant, unresolved
therapeutic challenge. Its aggressive features include insidious presentation,
unresectability due to early involvement of major vessels, debilitating symptoms
at the late stage and de novo chemoresistance.
However, according to the Japan Pancreatic Cancer Registry, the 5-year survival
of UICC Stages 0 and 1a are 85.8% and 68.7%, respectively.
Early diagnosis plays an important role in improving the overall survival of
patients with PDAC; therefore, efforts should focus on early diagnosis and the
reliable identification of patients who will most likely benefit from major surgical
intervention.
Patients with risk factors, including family history, accompanying disease,
diabetes mellitus, chronic pancreatitis and intraductal papillary mucinous
neoplasms (IPMN), should be followed up for early detection of PDAC. In Japan,
a national team has undertaken such surveillance of patients with IPMN. The
protocol comprises a semi-annual follow up using various modalities to detect
not only IPMN carcinoma, but also PDAC concomitant with IPMN. I will address
this protocol in detail.
The most accurate imaging technique for PDAC diagnosis and staging is
considered to be contrast-enhanced computed tomography (CECT). Whereas
CT should be the first choice in patients with suspected PDAC, endoscopic
ultrasound (EUS) is the most accurate, particularly for detecting small lesions (<
10 mm). EUS combines the potential of endoscopy, which enables visualization
of the mucosal surface of the gastrointestinal (GI) tract, with ultrasonography.
Thus, EUS is able to provide detailed, high-resolution images of the pancreas.
However, whether a lesion is malignant or benign is unable to be discriminated
solely from EUS imaging features. Obtaining samples from suspicious lesions or
lymph nodes using EUS-guided fine-needle aspiration (FNA), offers the potential
for cytological or histological diagnoses of pancreatic lesions with high sensitivity
and specificity. Since accurate preoperative evaluation is essential to select the
appropriate management strategy, the roles of EUS and EUS-FNA are crucial.
Stage 0 PDAC (carcinoma in situ) has recently been discovered. This stage of PDAC
is unable to be diagnosed using EUS-FNA, because EUS-FNA is only applicable
after PDAC forms a cancerous mass (worse than stage1). Thus, diagnostic methods
other than imaging require development. Presently, endoscopic retrograde
pancreatography (ERP) combined with cytology is able to detect Stage 0 PDAC,
and in Japan, nasopancreatic drainage tubes have recently been used to collect
pancreatic juice for cytodiagnosis. I would also like to introduce this method.
2. Diagnosis of pancreatic ductal carcinoma
Susumu HIJIOKA ; Kazuo HARA ; Nobumasa MIZUNO ; Hiroshi IMAOKA ; Kenji YAMAO
Innovation 2014;8(4):100-101
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of gastrointestinalcancer, with a 5-year survival rate of 5%; it remains a significant, unresolvedtherapeutic challenge. Its aggressive features include insidious presentation,unresectability due to early involvement of major vessels, debilitating symptomsat the late stage and de novo chemoresistance.However, according to the Japan Pancreatic Cancer Registry, the 5-year survivalof UICC Stages 0 and 1a are 85.8% and 68.7%, respectively.Early diagnosis plays an important role in improving the overall survival ofpatients with PDAC; therefore, efforts should focus on early diagnosis and thereliable identification of patients who will most likely benefit from major surgicalintervention.Patients with risk factors, including family history, accompanying disease,diabetes mellitus, chronic pancreatitis and intraductal papillary mucinousneoplasms (IPMN), should be followed up for early detection of PDAC. In Japan,a national team has undertaken such surveillance of patients with IPMN. Theprotocol comprises a semi-annual follow up using various modalities to detectnot only IPMN carcinoma, but also PDAC concomitant with IPMN. I will addressthis protocol in detail.The most accurate imaging technique for PDAC diagnosis and staging isconsidered to be contrast-enhanced computed tomography (CECT). WhereasCT should be the first choice in patients with suspected PDAC, endoscopicultrasound (EUS) is the most accurate, particularly for detecting small lesions (<10 mm). EUS combines the potential of endoscopy, which enables visualizationof the mucosal surface of the gastrointestinal (GI) tract, with ultrasonography.Thus, EUS is able to provide detailed, high-resolution images of the pancreas.However, whether a lesion is malignant or benign is unable to be discriminatedsolely from EUS imaging features. Obtaining samples from suspicious lesions orlymph nodes using EUS-guided fine-needle aspiration (FNA), offers the potentialfor cytological or histological diagnoses of pancreatic lesions with high sensitivityand specificity. Since accurate preoperative evaluation is essential to select theappropriate management strategy, the roles of EUS and EUS-FNA are crucial.Stage 0 PDAC (carcinoma in situ) has recently been discovered. This stage of PDACis unable to be diagnosed using EUS-FNA, because EUS-FNA is only applicableafter PDAC forms a cancerous mass (worse than stage1). Thus, diagnostic methodsother than imaging require development. Presently, endoscopic retrogradepancreatography (ERP) combined with cytology is able to detect Stage 0 PDAC,and in Japan, nasopancreatic drainage tubes have recently been used to collectpancreatic juice for cytodiagnosis. I would also like to introduce this method.
3.Regulation of the Wnt Signaling Pathways during Cell Culture of Human Mesenchymal Stem Cells for Efficient Bone Regeneration
Wataru Katagiri ; Yoichi Yamada ; Sayaka Nakamura ; Kenji Ito ; Kenji Hara ; Hideharu Hibi ; Minoru Ueda
Oral Science International 2010;7(2):37-46
Tissue engineering and bone regeneration techniques using mesenchymal stem cells (MSCs) have started to be applied to the field of oral and maxillofacial surgery. Clinically, a shortened treatment time and improved efficiency are necessary because of the patients' needs and the running cost of cell culture. In the present study, the cultivation process for human MSCs (hMSCs) was examined by regulating the Wnt signaling pathway. We activated Wnt signaling with LiCl and inhibited Wnt signaling with sFRP-3 (secreted Frizzled-Related Protein-3). The proliferation of LiCl-treated hMSCs was examined by studying the cell growth rate and performing BrdU assays. Osteogenic differentiation of sFRP-3-treated hMSCs was examined by alizarin red staining, and osteogenic gene expression on days 7 and 14 after induction was examined by reverse-transcription polymerase chain reaction (RT-PCR) analysis and quantitative real-time RT-PCR analysis. LiCl-treated hMSCs showed increased cell numbers and BrdU-positive cells as compared to the untreated cells. Alizarin red staining showed early mineralization of hMSCs on day 7 of the sFRP-3 treatment. A high expression level of the alkaline phosphatase gene on days 7 and 14 of sFRP-3 treatment was also demonstrated. These results suggest that the regulation of the Wnt signaling pathway contributes to the increased cell numbers and the early osteogenic differentiation of hMSCs. This study supports the possibility that the regulation of the Wnt signaling pathway contributes to the development of effective and efficient bone regeneration techniques.
4.Training in Medical Communication Skills by Role-play in Jichi Medical School.
Hideaki IMAMICHI ; Kenji HARA ; Masato SASAKI ; Katsumi IIJIMA ; Mitsuki NIREKI ; Masahiro IGARASHI
Medical Education 1996;27(4):247-252
The Jichi Medical School has trained doctors for work in community health care for over 20 years.Students learn medical communication skills by role-play. In this role-play, doctors and patients areplayed by students. Discussions are also held by students. The teaching staff give additional explanations, suggestions and demonstrations. By themselves, students learn about 1) general practice, 2) theprocess of consultation, 3) medical communication and 4) patients' emotions. We plan to develop othereducational resources such as trained simulated patients.
5.Activity of the Athletic Trainer in a collegiate boxing club-investigation on acupuncture for boxers-
Shigeki IZUMI ; Toshikazu MIYAMOTO ; Kenji HARA ; Sachiko IKEMUNE ; Masahumi HORI ; Hiroshi NISHIMURA ; Shumpei MIYAKAWA
Journal of the Japan Society of Acupuncture and Moxibustion 2006;56(5):815-820
[Objective] To report the activity by the athletic trainer in a collegiate boxing club, focusing on acupuncture for medical treatment.
[Methods] The athletic trainer was Japan a Japan Sports Association certifiedathletic trainer who was a practitioner of acupuncture and moxibustion. Subjects were twenty-seven collegiate boxers who participated for one year from April, 2004 to March, 2005.
[Results] The activity by the athletic trainer was performed for thirty two days. Medical treatment was performed up to 2.2 times a day. Seventy-one people were treated by the athletic trainer. Medical treatments were acupuncture 28 (39.4%), massage 24 (33.8%), taping 4 (5.6%), and partner stretch 3 (4.2%). Thirteen people (48.1%) had acupuncture. In acupuncture, fifteen people (50%) had a chief complaint in the hand.
[Discussion] Acupuncture was requested by the boxers. The continuation of the activity by the athletic trainer was required for boxing.
6.Serum lipid levels in female handball players.
KENJI TAKAGI ; KAZUTADA OKUMURA ; NORIYUKI MORIKAWA ; GOUICHIROU KAJIYAMA ; SHINPEI HARA ; YUZO SATO
Japanese Journal of Physical Fitness and Sports Medicine 1991;40(2):202-207
Serum lipid levels in female handball players were studied. A group of well trained female handball players, in comparison with a group of less active females, had a significantly lower level of triglyceride, higher levels of HDL-cholesterol and HDL2-Cholesterol subfractions, and higher apolipoprotein A-I and LCAT activities. The ratio of apolipoprotein B/apolipoprotein A-I, as an atherogenic index, was also significantly lower in the handball players. These results suggest that prolonged regular exercise such as handball training may produce favorable changes in serum lipids, thus helping to prevent and reduce the incidence of atherosclerosis.
7.The effect of the electroacupuncture therapy for low back pain of collegiate athletes
Shigeki IZUMI ; Toshikazu MIYAMOTO ; Takahiro KOBORI ; Kensuke AOKI ; Sachiko IKEMUNE ; Kenji HARA ; Shoko KATAYAMA ; Shumpei MIYAKAWA
Journal of the Japan Society of Acupuncture and Moxibustion 2008;58(5):775-784
[Objective]The purpose of this study is to evaluate an effect of electroacupuncture therapy on low back pain of collegiate athletes.
[Methods]Subjects were 28 collegiate athletes with low back pain who gave informed consent. They consulted a medical doctor beforehand. The electroacupuncture therapy was performed as acupuncture. The evaluation items were as follows:Visual Analogue Scale (VAS) which expresses the state of the pain (Pain-VAS), VAS which shows a training state (Training-VAS), five phases of evaluations to show a training state, pain at the time of the trunk movements, Roland-Morris Disability Questionnaire (RDQ), and Japanese Orthopedic Association (JOA) score. The correlation of each item was estimated.
[Results]The chief complaint of 27 people was low back pain, and one person had pain of the low back and the lower extremities. In the diagnosis, 16 people had non-specific low back pain, 5people had lumbar vertebrae discopathy, and 3had a lumber vertebrae herniated disk. As a result of acupuncture, the training-VAS and five phases of evaluations to show the training state and JOA score were significantly improved. However, as for the pain-VAS and pain at the time of trunk movements and RDQ, a significant difference was not accepted.
[Conclusion]Training-VAS is useful for measuring the outcome of an athlete with low back pain. It is important that athletes with low back pain evaluate their training.
8.Results of Laminoplasty for Cervical Spondylotic Myelopathy.
Akihiko OKAMOTO ; Masafumi ISHIZUKI ; Yasushi ISOBE ; Norio SAITOH ; Masami TOMINAGA ; Hidehiko OZAWA ; Taisuke TANIZAWA ; Yasuo SUGATA ; Tomoyuki MOCHIZUKI ; Kenji HARA ; Kazuyuki SAKAI
Journal of the Japanese Association of Rural Medicine 2001;49(5):729-732
[Follow-up studies were made of 35 patient who underwent laminoplasty for cervical spondylotic myelopathy for 22 monthoon averages]
The conditions of 35 patients were observed consecutively after laminoplasty.
The mean JOA scores were improved from 8.7 to 12.5. Postoperative JOA scores correlated with preoperarive JOA scores (r=0.60, p<0.01) and ages at the time of the operation (r=-0.45, p<0.01). The period from the onset of the disease to the operation and the vertebral canal diameters didnot [No significant correlation who found between- and-] influence the operative results of the operation.
9.Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?
Tsukasa Yoshida ; Susumu Hijioko ; Waki Hosoda ; Nobumasa Mizuno ; Kazuo Hara ; Hiroshi Imaoka ; Vikram Bhatia ; Masahiro Tajika ; Mohamed A Mekky ; Makoto Ishihara ; Tatsuji Yogi ; Kenji Yamao
Innovation 2014;8(4):124-125
Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)
in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67
labeling index (LI). However, the clinical behavior of NEC is still not fully studied.
We aimed to clarify the clinicopathological and molecular characteristics of
NECs.
Methods: We retrospectively evaluated the clinicopathological characteristics,
KRAS mutation status, treatment response, and the overall survival of eleven
pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.
We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiated
NEC (PDNEC), the latter further subdivided into large and small
cell type.
Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the median
tumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7
PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.
Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)
vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -
95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); response
rates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) and
median survival, 227 vs. 186 days (P = 0.227).
Conclusions: The WHO-NEC category may be composed of heterogeneous
disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit
differing Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.
Further studies for the re-evaluation of the current WHO 2010 classification is
warranted.
10. Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?
Tsukasa YOSHIDA ; Susumu HIJIOKO ; Waki HOSODA ; Nobumasa MIZUNO ; Kazuo HARA ; Hiroshi IMAOKA ; Vikram BHATIA ; Masahiro TAJIKA ; Mohamed A Mekky ; Makoto ISHIHARA ; Tatsuji YOGI ; Kenji YAMAO
Innovation 2014;8(4):124-125
Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67labeling index (LI). However, the clinical behavior of NEC is still not fully studied.We aimed to clarify the clinicopathological and molecular characteristics ofNECs.Methods: We retrospectively evaluated the clinicopathological characteristics,KRAS mutation status, treatment response, and the overall survival of elevenpNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiatedNEC (PDNEC), the latter further subdivided into large and smallcell type.Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the mediantumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); responserates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) andmedian survival, 227 vs. 186 days (P = 0.227).Conclusions: The WHO-NEC category may be composed of heterogeneousdisease entities, namely WDNEC and PDNEC. These subgroups tended to exhibitdiffering Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.Further studies for the re-evaluation of the current WHO 2010 classification iswarranted.