bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrence after endoscopic mucosal resection of esophageal squamous cell carcinoma invading the muscularis mucosae or upper submucosa
Authors: Shimizu Yuichi , Tsukagoshi Hiroyuki , Fujita Masahiro , Hosokawa Masao , Kato Mototsugu , Asaka Masahiro
Published: September 2003

Background:  Endoscopic mucosal resection (EMR) is recommended for cases of squamous cell carcinoma of the esophagus in which the tumor is confined to the lamina propria mucosa. However, EMR is often performed in patients whose tumors invade the muscularis mucosae (m3) or upper submucosa (sm1) to minimize surgical invasion, despite the increased risk of lymph node metastasis. We evaluated patients who were found to have distant or lymph node metastasis after EMR for such lesions.

Methods:  Thirty‐four consecutive patients with esophageal carcinoma invading m3 or sm1 who underwent EMR during the period from June 1992 through March 2001 (extended EMR group) were studied.

Results:  Five of these patients were found to have distant or lymph node metastasis on follow up. Patient 1 died of lung metastasis 34 months after EMR. Patient 2 underwent chemotherapy because of an abnormally high value of squamous cell carcinoma (SCC) antigen. Patient 3 died of upper mediastinal lymph node metastasis 62 months after EMR. Patient 4 underwent total gastrectomy because of gastric wall metastasis 41 months after EMR and underwent chemoradiotherapy because of upper mediastinal lymph node metastasis 87 months after EMR. Patient 5 was found to have cardiac lymph node metastasis by follow‐up endoscopic ultrasonography examination 42 months after EMR and underwent curative lymph node dissection.

Conclusion:  It is unlikely that patient 1 and patient 2, both with probable distant metastasis, received inadequate treatment. Surgery with lymph node dissection usually cannot prevent distant metastasis. The patients with lymph node recurrence (patient 3 and patient 4) should have been followed up more carefully. We believe that patients with early lymph node metastasis, such as patient 5 in this study, should undergo curative surgical resection. Patients undergoing extended EMR should be carefully followed up for a long period to enable early detection and treatment of lymph node metastasis.
Experience with electronic radial endoscopic color Doppler ultrasonography in esophageal variceal patients
Authors: Sato Takahiro , Yamazaki Katsu , Toyota Jouji , Karino Yoshiyasu , Ohmura Takumi , Akaike Jun , Kuwata Yasuaki , Suga Toshihiro
Published: September 2003

Background:  Endoscopic color Doppler ultrasonography (ECDUS) is a method for detecting color flow images in blood vessels. In the present study, electronic radial ECDUS in cases of esophageal varices is described.

Methods:  Thirteen patients with esophageal varices were studied. The technique of ECDUS was performed using a Pentax EG3630‐UR (forward‐view) with a distal tip diameter of 12 mm. The instrument (electronic radial array) has a curved array scanning transducer with variable frequency (5.0, 7.5, 10.0 MHz) and B mode/color Doppler/power Doppler capability. A Hitachi EUB 6500 was used for the display, providing a 270° image. We monitored the color flow images of esophageal varices, paraesophageal veins and perforating veins using this technique.

Results:  Color flow images of esophageal varices and paraesophageal veins were obtained in 13 of the 13 patients, whereas color flow images of perforating veins were obtained in four of the 13 patients (30.8%). The 13 esophageal varices exhibited velocities ranging between 3.0 and 11.7 cm/s (mean = 6.3 cm/ s). The forward‐viewing optics facilitated insertion, but the stiffness of the distal tip limited the flexibility of the scope, especially when attempting J‐ or U‐turn views.

Conclusion:  Electronic radial ECDUS provides color flow images similar in quality to those of convex‐type ECDUS with the additional advantages of forward‐view optics and extended 270° views.
Learning curve for laparoscopy‐assisted distal gastrectomy
Authors: Yasuda Kazuhiro , Shiraishi Norio , Inomata Masafumi , Fujii Kyuzo , Sonoda Kazuya , Kitano Seigo
Published: September 2003

Background:  Laparoscopy‐assisted distal gastrectomy (LADG) has proved to be useful in the management of early gastric cancer. The aim of the present study was to examine the learning curve for LADG and clarify any technical problems.

Methods:  The study included 75 consecutive patients who underwent LADG between 1994 and 2002. All operations were performed by a single surgeon and with a surgical team who were skilled in laparoscopic procedures, but new to LADG. Patients were divided into three groups according to the surgeon's level of experience at the time of surgery: Group I (n = 25, surgeries performed between November 1994 and April 1997), Group 2 (n = 25, surgeries performed between May 1997 and January 2000), and Group 3 (n = 25, surgeries performed between February 2000 and August 2002). We considered Groups 1, 2 and 3 to reflect the surgeon's beginning, intermediate and advanced levels of experience, respectively. Operation time, blood loss and incidence of complications were analyzed and compared between groups.

Results:  Operation time and blood loss did not differ between Groups 1, 2 and 3 (operation time: 236 vs 258 vs 225 min; blood loss: 157 vs 198 vs 144 mg, respectively). Postoperative complications occurred in nine patients (12%); the incidence did not differ between groups. The most frequent complication was wound infection (4%), followed by anastomotic stenosis (3%). There were no intraoperative complications or conversions to open surgery.

Conclusions:  There is no learning curve for LADG, when it is performed by a skilled surgeon and surgical team. Proficiency in basic laparoscopic techniques and open gastric surgery is easily adapted to safe completion of LADG.
Endoscopic removal of a dislocated covered wallstent using a wire‐loop technique
Authors: Itoi Takao , Nakamura Kazuto , Sofuni Atsushi , Itokawa Fumihide , Moriyasu Fuminori , Tsuchida Akihiko
Published: September 2003

Background:  Self‐expandable metallic stents (SEMS) and covered‐SEMS (cSEMS) are used for patients with unresectable malignant biliary strictures. Occasionally, there are cases where stent migration can easily occur.

Methods and Results:  We experienced a dislocated distal cSEMS that was unable to be removed by previously described techniques. However, we could successfully remove cSEMS with a wire‐loop technique using a polypectomy snare and guidewire.

Conclusion:  This technique may provide hope for the removal of severely dislocated cSEMS.
Polypoid cavernous hemangioma removed under colonoscopy
Authors: Kiba Takayoshi , Takemura Masanobu
Published: September 2003

A 57‐year‐old Japanese man was admitted to Ushioda General Hospital because of a positive fecal occult blood test. Colonoscopy revealed a pedunculated polyp in the ascending colon, which was removed by snare polypectomy with electrocautery. The resected polyp was bluish and measured 25 × 20 mm. Histological examination of the polyp revealed a cavernous hemangioma. The hemangioma infiltrated into the muscular layer; however, massive hemorrhage or perforation was not revealed. Although complications of colonoscopic excision of hemangiomas appear to be rare, the number of reports is small and it is, therefore, difficult to determine the safety of colonoscopic treatment.
Huge submucosal hematoma of the stomach after accidental removal of the PErcutaneous endoscopic gastrostomy tube
Authors: Chikamori Fumio , Kuniyoshi Nobutoshi , Kawashima Takahiko , Takase Yasuhiro
Published: September 2003

We report a case of massive hemorrhage and aspiration pneumonia as complications of percutaneous endoscopic gastrostomy (PEG). Three months after insertion of a PEG tube, the patient accidentally pulled out the tube by himself. After the accident, the patient experienced hematemesis, which caused aspiration pneumonia. The button‐type tube was reinserted into the PEG fistula for hemostasis. The bleeding stopped temporarily; however, 21 days later, the patient relapsed into a condition of massive PEG site bleeding and hematemesis. He was transferred to our hospital, Kuniyoshi Hospital, to control the bleeding and aspiration pneumonia. Endoscopy revealed a sliding type of large hiatal hernia and a huge submucosal hematoma with an ulceration at the lower part of the gastric body. Emergency surgery including local gastrectomy, gastrostomy, jejunostomy and tracheostomy were helpful to treat these complications. Endoscopists should be aware how to treat these complications. One should not hesitate to perform open surgery when other treatments fail.
Mirizzi syndrome Type IV: A rare entity
Authors: De Almeida Artifon Everson Luiz , Sakai Paulo , Hondo Fábio Yuji , Noda Rafael William , Ishioka Shinichi
Published: September 2003

Mirizzi's syndrome, characterized by obstructive jaundice due to an extrinsic compression of common hepatic duct by an impacted gallstone in the cystic duct or the neck of the gallbladder, is a rare complication of gallstone disease. The present case describes Mirizzi's syndrome classified as Type IV in a 50‐year‐old man with obstructive jaundice. Abdominal computed tomography scan demonstrated a dilated intrahepatic biliary tree and a tumoral mass at the porta hepatis, suggesting cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography also suggested cholangiocarcinoma involving the entire circumference of the common hepatic duct in porta hepatis. The diagnosis of Mirizzi's syndrome Type IV was confirmed during cholecystectomy, withdrawal of gallstone and Roux‐en‐Y hepaticojejunostomy.
Laparoscopic findings of liver cirrhosis due to non‐alcoholic steatohepatitis
Authors: Miyake Teruki , Michitaka Kojiro , Abe Masanori , Konishi Ichiro , Tokumoto Yoshio , Kumagi Teru , Nakanishi Seiji , Minami Hisaka , Matsui Hidetaka , Matsuura Bunzo , Horiike Norio , Onji Morikazu
Published: September 2003

A 42‐year‐old Japanese man was admitted to our hospital for investigation of abnormal liver function tests. He had no history of drug use, and drank little alcohol. Body mass index was 30. Serum was negative for viral markers and autoantibodies. Laparoscopy revealed diffuse small nodules on the liver surface. Liver biopsy revealed small nodules with pericellular fibrosis and macrovesicular fat deposition throughout the acini. Some inflammatory changes were observed. Liver cirrhosis due to non‐alcoholic steatohepatitis (NASH) was diagnosed. NASH displays similar histological and laparoscopic characteristics to alcoholic liver diseases.
Surveillance colonoscopy for colitic cancer in inflammatory bowel disease
Authors: Hata Keisuke , Watanabe Toshiaki , Nagawa Hirokazu
Published: September 2003

Patients with inflammatory bowel disease are known to be at increased risk for the development of colorectal cancer, especially those with long‐standing extensive ulcerative colitis. Although some recommend prophylactic total proctocolectomy for these high‐risk patients, surveillance colonoscopy to detect ulcerative colitis‐associated colorectal cancer is, instead, generally performed. Dysplasia has been considered to be a useful marker to detect colorectal cancer at surveillance colonoscopy. High‐grade dysplasia is a definite indication for total proctocolectomy, while management of low‐grade dysplasia is still controversial. Patients with Crohn's disease are also considered to be at higher risk for the development of colorectal cancer, although the risk may be lower than in extensive ulcerative colitis. Molecular biology‐based surveillance and chemoprevention for ulcerative colitis‐associated colorectal cancer are also reviewed.
Comparison of histological analysis and endosonographic features in esophageal granular cell tumors
Authors: Yazumi Shujiro , Takahashi Rei , Kajiyama Toru , Nakase Hiroshi , Watanabe Norihiko , Ohana Masaya , Matsumoto Shigemi , Seno Hiroshi , Sawada Mitsutaka , Uchida Kazushige , Nabeshima Motoshige , Okazaki Kazuichi , Chiba Tsutomu
Published: September 2003

Background:  The increased use of esophagogastroduodenoscopy has revealed the esophagus to be a common site of occurrence of granular cell tumors (GCT). To clarify the endosonographic features of esophageal GCT, we compared endosonographic findings and histopathological analysis of resected specimens of esophageal GCT and submucosal leiomyomas.

Methods:  We enrolled a total number of 18 consecutive patients with esophageal submucosal tumors. They were preoperatively examined using 15 MHz or 20 MHz probe endoscopic ultrasonography. The endosonographic findings were retrospectively compared with hisopathological findings of the resected specimens.

Results:  Five GCT and 13 submucosal leiomyomas were diagnosed histologically as well as endosonographically. Pathological analysis revealed that the dispropotional mixture of tumor cells, fibrosis and muscularis mucosa within the GCT would be endosonographically visualized as a heterogeneous hypoechoic mass. Moreover, the laterally scattered tumor cells, together with adjacent thickened muscularis mucosa, are reflected by the unclear margin of the tumor by endoscopic ultrasonography. In contrast, in the submucosal leiomyomas, tumor cells and fibrosis were uniformly mixed and the margin of the tumor was clearly demarcated. These histological findings would be endosonographically recognized as a homogeneously hypoechoic mass with a clearly demarcated border.

Conclusion:  A high‐frequency probe endoscopic ultrasonography is useful for differentiating esophageal GCT from submucosal leiomyomas. Considering the histological characteristics, esophageal GCT should be resected with adequate tumor‐free margin when endoscopic treatment is applied.
Laparoscopic findings in non‐alcoholic steatohepatitis
Authors: Seki Shuichi , Sakaguchi Hiroki , Kitada Takuya , Iwai Shuji , Fujii Hideki , Enomoto Masaru , Habu Daiki , Tamori Akihiro
Published: September 2003

Background:  Non‐alcoholic steatohepatitis (NASH) is prevalent worldwide, but little attention has been paid to the gross visual appearance of NASH. The present study was performed to address the laparoscopic features of NASH and the relationship between laparoscopic and histologicalal findings.

Methods:  Eleven patients were examined by laparoscopy with liver biopsy. Histological findings were examined according to the criteria of Brunt et al. with minor modification. Mallory bodies were immunohistochemically detected by an antibody to ubiquitin in addition to hematoxylin eosin staining.

Results:  Laparoscopic features of NASH were swelling of the liver, formation of many depressions, and dull edges of the liver. When steatosis was present in more than one‐third of lobules, yellowish markings appeared on the liver surface. NASH progressed from a smooth liver surface with or without yellowish markings, to formation of depressions on the liver surface, to cirrhosis with or without hepatocellular carcinoma (HCC).

Conclusion:  Laparoscopy may provide useful information in the diagnosis and progression of NASH.
Clipless laparoscopic restorative proctocolectomy using an electrothermal bipolar vessel sealer
Authors: Hasegawa Hirotoshi , Watanabe Masahiko , Nishibori Hideki , Ishii Yoshiyuki , Kitajima Masaki
Published: September 2003

Background:  Recently, a new type of laparoscopic electrothermal bipolar vessel sealer (EBVS; LigaSure Atlas) was developed. The aim of the present study was to describe the feasibility and effectiveness of LigaSure Atlas in laparoscopic restorative proctocolectomy for patients with ulcerative colitis.

Methods:  Between January and December 2002, eight patients with ulcerative colitis underwent laparoscopic restorative proctocolectomy. The median age was 30 (range: 18–51) years and median follow up was 6 (range: 1–13) months. The entire procedure was performed using only LigaSure Atlas and diathermy, without using conventional hemoclips or ultrasonic coagulating shears.

Results:  There were no conversions to the open procedure. There were no intraoperative or postoperative hemorrhagic complications. The operative time was reduced by 40 min compared with the conventional laparoscopic procedure, and the cost was 350 US dollars less compared with the method using conventional hemoclips and ultrasonic coagulating shears.

Conclusion:  The laparoscopic restorative proctocolectomy using LigaSure Atlas is safe, feasible and cost‐effective in selected patients with ulcerative colitis.
Hemodynamics of esophageal varices on three‐dimensional endoscopic ultrasonography and indication of endoscopic variceal ligation
Authors: Nakamura Shinichi , Murata Yoko , Mitsunaga Atsushi , Oi Itaru , Hayashi Naoaki , Suzuki Shigeru
Published: September 2003

Background:  Esophageal varices are treated by endoscopic variceal ligation or sclerotherapy, but the indications for each procedure are not standardized. The present study was designed to determine the indication of endoscopic variceal ligation based on vascular pattern classified by 3‐dimensional endoscopic ultrasonography (3‐D‐EUS).

Methods:  The pattern of variceal blood flow detected on 3‐D images was classified into type 1 (cardial‐inflow without paraesophageal veins), type 2 (cardial‐inflow with paraesophageal veins), type 3 (azygos‐perforating pattern) and type 4 (complex pattern). 3‐D‐EUS was performed in 89 patients with esophageal varices. Subsequently, ligation was performed in 44 patients, while sclerotherapy with 5% ethanolamine oleate was applied in 45 patients in a prospective randomized trial. Clinical outcome was assessed.

Results:  Based on the 3‐D‐EUS data, 41 patients (46.1%) were classified as type 1, 12 (13.5%) as type 2, seven (7.9%) as type 3 and 29 patients (32.6%) as type 4. The cumulative recurrence‐free probability at 24 months after treatment was 28.9% for ligation versus 71.1% for sclerotherapy (P < 0.05) in type 1, while the respective probabilities were 72.9% versus 50.0% (NS) for type 2 varices, 100% versus 100% (NS) for type 3 varices and 61.9% versus 64.8% (NS) for type 4 varices.

Conclusions:  Classification of the vascular pattern of esophageal varices by 3‐D‐EUS enabled us to clarify the criteria for selection of endoscopic procedure. Ligation is indicated for patients who have collaterals, such as paraesophageal veins running parallel to the varices, as the blood flow can be diverted to these blood vessels and controlled by localized ligation.
Clinical role of endoscopic ultrasonography for the diagnosis of early colorectal cancer and selecting the treatment procedure
Authors: Kobayashi Kiyonori , Kida Mitsuhiro , Katsumata Tomoe , Yoshizawa Shigeru , Yokoyama Kaoru , Sada Miwa , Igarashi Masahiro , Saigenji Katsunori
Published: September 2003

Background:  Accurate evaluation of the depth of tumor invasion, including the degree of submucosal invasion, is a prerequisite to selecting the treatment procedure for early colorectal cancer (CRC). The purpose of the present study was to evaluate the significance of endoscopic ultrasonography (EUS) for diagnosing the depth of invasion of early CRC and selecting the treatment procedure. We concurrently estimated the usefulness of three‐dimensional EUS (3‐D‐EUS) compared with that of conventional EUS.

Methods:  We studied 413 consecutive early CRC for which the depth of invasion was examined by EUS. They consisted of 239 lesions of mucosal cancers and 174 lesions of submucosal cancers (sm cancers). We divided sm cancers into two groups, sm‐slight cancers (38 lesions) and sm‐massive cancers (136 lesions), according to the degree of infiltration in the vertical direction in the submucosa. The diagnostic accuracy of the depth of cancerous invasion by EUS and the characteristics of tumors that were difficult to image by EUS were examined. For 59 lesions, the depth of invasion was concurrently evaluated by 3‐D‐EUS to compare the clinical usefulness of this diagnostic tool with that of conventional EUS.

Results:  In 364 lesions (88%) of early CRC, we could diagnose the depth of invasion by EUS. Differentiation between mucosal or sm‐slight cancers, which were generally treated by endoscopic resection or local excision, and sm‐massive cancers, which were suitable for radical operation, was possible in 90%. A total of 49 lesions (12%) could not be imaged by EUS. Difficulty in imaging often occurred with lesions located proximally to the transverse colon and with protruded‐type lesions. The accuracy rate of 3‐D‐EUS for differentiating between mucosal or sm‐slight cancers and sm‐massive cancers, including difficult‐to‐image lesions, was 86%. This figure was slightly, but not significantly higher, than the accuracy rate of 73% for conventional EUS (P = 0.07). However, the concurrent application of 3‐D‐EUS was considered useful in 31 of the 59 lesions (53%) evaluated by both techniques.

Conclusion: EUS is useful for evaluating the depth of tumor invasion and selecting the treatment procedure for early CRC. The concurrent use of 3‐D‐EUS may further improve diagnostic accuracy and decrease the number of difficult‐to‐image lesions.
Association of testicular undescent induced by prenatal flutamide treatment with thickening of the cremaster muscle in rats
Authors: Matsuno Yoshiharu , Komiyama Masatoshi , Tobe Toyofusa , Toyota Naoji , Adachi Tetsuya , Mori Chisato
Published: September 2003

Background and Aims:  Previously, in cryptorchid rats, which were induced by prenatal exposure to flutamide, we found a thickening of the cremaster muscle. This study was undertaken to quantify the increase of the cremaster muscle thickness in the cryptorchid rats, and to examine its possible relationship with the proliferation of muscle cells.

Methods:  To obtain cryptorchid rats, pregnant Wistar rats were subcutaneously injected with flutamide (100 mg/kg per day) during gestational days 16–17. Serial sections of the scrotum, containing the testis and cremaster muscle, were prepared from the control and cryptorchid rats that were 2–6 weeks of age, and stained with hematoxylin–eosin for morphometry, or stained with antibody against the proliferating cell nuclear antigen (PCNA) to analyze the cell proliferation ability.

Results:  The thickened cremaster muscle was always associated with cryptorchid testis and, in the case of unilateral cryptorchidism, the cremaster muscle of the contralateral (descended testis) side exhibited normal thickness. The average thickness of the affected cremaster muscle was 0.80 and 1.89 mm at 4 and 6 weeks of age, respectively, although that of the normal muscle was 0.28 and 0.33 mm at the same time period, respectively.

Conclusion:  Our results showed that the cremaster muscle of the cryptorchid rats was significantly thicker than that of the control rats. The immunohistochemical analysis revealed that a thickened cremaster muscle contained many PCNA‐positive nuclei even at 4 weeks of age, in contrast to the control, which had only a few positive nuclei. Our present study indicates that continuous proliferation of the muscle cells associated with cryptorchid testis increases the thickness of cremaster cells in rats exposed to flutamide prenatally. (Reprod Med Biol 2003; 2: 109–113)
Infertile women without sensitization to an appropriate amount of sperm do not produce sperm‐immobilizing antibodies in their sera
Authors: Shibahara Hiroaki , Kikuchi Kumiko , Shiraishi Yasuko , Suzuki Mitsuaki , Shigeta Minoru , Koyama Koji
Published: September 2003

Background and Aim:  The factors that affect sperm immobilizing antibody production in some women are not fully understood. This study was performed to investigate if production of sperm immobilizing antibodies in women is associated with their husbands’ sperm count.

Methods:  The sperm immobilization test (SIT) was performed on 221 infertile women whose husbands had normal semen characteristics according to the criteria by WHO; 160 patients were treated by intracytoplasmic sperm injection (ICSI) because of poor semen characteristics, and 1013 virgin female children acted as the controls.

Results:  A significant difference of the incidence in SIT was observed between the virgin female children and the women whose husbands had a normal sperm count (P < 0.0001). There was also a significant difference of the incidence in SIT between the women treated by intracytoplasmic sperm injection (ICSI) because of a severe male factor and those whose husbands had a normal sperm count (P < 0.05).

Conclusions:  These results indicate that production of sperm immobilizing antibodies in women begins after they have been exposed to a large enough amount of sperm. However, the precise amount of sperm required to produce the antibodies is not clarified by the present study. (Reprod Med Biol 2003; 2: 105–108)
G2/M transition of pig oocytes: How do oocytes initiate maturation?
Authors: Miyano Takashi , Lee Jibak , Fulka Josef
Published: September 2003

In the ovary, mammalian oocytes resume meiosis and mature to the second metaphase when they are stimulated with gonadotrophins. Similarly, oocytes can mature in vitro when they are liberated from ovarian follicles and cultured under appropriate conditions. Early in the process of maturation, oocytes undergo dramatic but well‐ordered changes at the G2/M transition in the cell cycle including: (i) chromosome condensation; (ii) nucleolus disassembly; (iii) germinal vesicle breakdown (GVBD); and (iv) spindle formation in the first metaphase (MI‐spindle). These events have been thought to be induced by MPF (maturation‐promoting factor or M‐phase promoting factor), now known as Cdc2 kinase or Cdk1 kinase, which consists of a catalytic subunit, Cdc2, and a cyclin B regulatory subunit. In fact, nuclear lamins are phosphorylated by Cdc2 kinase, and nuclear membrane breakdown occurs concomitantly with the activation of Cdc2 kinase in the M‐phase of both somatic cells and oocytes. Based on the classical and recent studies of the pig oocyte, however, the chromosomes start to condense and the nucleolus disassembles before full activation of Cdc2 kinase, and the MI‐spindle is formed after activation of both Cdc2 kinase and MAP kinase; another kinase known to become activated during oocyte maturation. These findings suggest that chromosome condensation and nucleolus disassembly in oocytes are induced by either some kinase(s) other than Cdc2 kinase and MAP kinase or some phosphatase(s). The accumulation of new results regarding the molecular nature of oocyte maturation is important for improving the reproductive technologies in domestic animals as well as in humans. (Reprod Med Biol 2003; 2: 91–99)
Identification of complexes of gelatinase A and tissue inhibitor of metalloproteinase‐2 in human follicular fluid
Authors: Shimokawa Ken‐Ichi , Katayama Masatoki , Matsuda Yoshifumi , Takahashi Hidenobu , Hara Izumi , Sato Hirohisa
Published: September 2003

Background and Aims:  Ovulation involves considerable tissue remodeling in normal ovarian function. These processes are expected to involve matrix metalloproteinases (MMP). Follicular rupture is caused by the degradation of the basement membrane between the thecal and granulose layers, as well as disruption of the extracellular matrix (ECM) at the site of rupture. We report on the existence of the complexes of progelatinase A (proMMP‐2), MMP‐2 and a tissue inhibitor of metalloproteinase‐2 (TIMP‐2) using zymographic and immunological techniques in human follicular fluid (HFF).

Methods and Results:  Partial purification of the complexes was achieved by using gelatin affinity column chromatography. The peak (tubes 68–73) in this chromatography showed gelatinase activities by gelatin‐zymography, and also an inhibition by EDTA (metalloproteinase inhibitor). The molecular weights of the gelatinase activities were approximately 72 and 67 kDa, and were consistent with standard proMMP‐2 and MMP‐2, as found by using gelatin‐zymography. Similarly, the band in this peak was consistent with standard recombinant full‐length TIMP‐2, as found by the use of western blot analysis, and the molecular weight of the band was approximately 21 kDa.

Conclusion:  As proMMP‐2, MMP‐2 and TIMP‐2 exist in the peak from the gelatin affinity column, we expected that these form the complexes. These results indicate that the complexes of proMMP‐2/TIMP‐2 and MMP‐2/TIMP‐2 exist in HFF. (Reprod Med Biol 2003; 2: 115–119)
Two‐step consecutive transfer of early embryos and blastocysts
Authors: Kyono Koichi , Fukunaga Noritaka , Chiba Setsuyo , Nakajo Yukiko , Fuchinoue Kohei , Yagi Akiko , Araki Yasuhisa
Published: September 2003

Aim:  To evaluate and confirm the merit of two consecutive transfer attempts of early embryos and blastocysts.

Methods:  A total of 685 patients underwent routine in vitro fertilization (IVF) cycles. The study population consisted of three groups: (i) Group 1, early stage embryos were transferred (460 patients; 567 cycles); (ii) group 2, blastocysts were transferred (88 patients; 105 cycles); and (iii) group 3, a two‐step (consecutive) transfer was performed on 137 women (141 cycles). Specifically, a standard embryo transfer was performed on day 3, together with a two‐step (consecutive) transfer of blastocysts. After the early embryo transfer, an extended culture of supernumerary embryos was conducted, followed by a second transfer of blastocyst(s).

Results:  No significant differences were found in the three groups with regards to either pregnancy or implantation rates for groups 1, 2, or 3; pregnancy: 34.6, 29.9, and 33.6%, respectively; implantation: 18.6, 15.9, and 15.1%, respectively. The miscarriage rate for each group was also not significant; 20.4, 30.8 and 28.6% for groups 1, 2 and 3, respectively. The multiple pregnancy rate of the three groups was 30.4, 30.8 and 35.7%, respectively, and these were not found to be significant results.

Conclusion:  No significant difference was found between the three groups with regards to the pregnancy, implantation, multiple pregnancy and miscarriage rates. The multiple pregnancy rate was highest in the two‐step (consecutive) transfer group. This difference was not regarded to be highly significant. (Reprod Med Biol 2003; 2: 133–137)
Activation of protein kinase C inhibits the secretion of platelet‐activating factor acetylhydrolase by human decidual macrophages
Authors: Narahara Hisashi , Utsunomiya Hiroko , Nishida Masakazu , Nasu Kaei , Kawano Yasushi , Miyakawa Isao
Published: September 2003

Background and Aims:  Platelet activating factor (PAF), a potent phospholipid mediator, has been implicated in a number of reproductive processes through ovulation to parturition. To clarify the regulatory mechanism of PAF metabolism in the decidua, we have investigated the effect of activation of protein kinase C (PKC) on the secretion of PAF‐acetylhydrolase (PAF‐AH), a PAF‐inactivating enzyme, by human decidual macrophages.

Methods:  Decidual macrophage populations were isolated from human decidua by using enzymic digestion, Ficoll–Paque centrifugation, or flow cytometric sorting. The cells were treated with a PKC activator (TPA), H‐7, dibutyryl cyclic adenosine monophosphate (AMP), Bis‐(o‐aminophenoxy)‐ethane‐N,N,N’,N’‐tetraacetic acid, tetra (acetoxymethyl)‐ester (BAPTA/AM) and/or nifedipine. The activity of PAF‐AH secreted in the culture medium was assayed.

Results:  The PKC activator, TPA, inhibited the PAF‐AH secretion by decidual cells in a dose‐dependent manner. The TPA also decreased the enzyme secretion by flow cytometrically purified macrophages. The inhibitory effect of TPA was blocked by a PKC inhibitor, H‐7. Protein kinase A (PKA) activation by dibutyryl cyclic AMP was without effect on the enzyme secretion. Calcium channel blockers, BAPTA/AM and nifedipine had no effect on the PAF‐AH secretion.

Conclusion:  It is suggested that the TPA‐induced inhibition of PAF‐AH secretion may be mediated, in part, by a PKC‐dependent signal transduction, and that activation of PKC may result in the increase in the local concentration of PAF in the decidua because of its inhibitory effect on the PAF‐AH secretion by decidual macrophages. (Reprod Med Biol 2003; 2: 121–126)
Clinical experience of vasoepididymostomy using a triangulation technique
Authors: Hibi Hatsuki , Ohori Tadashi , Amano Toshiyasu , Yamada Yoshiaki , Honda Nobuaki , Fukatsu Hidetoshi , Asada Yoshimasa
Published: September 2003

Background: Although the number of patients receiving vasoepididymostomies is gradually increasing, these individuals are limited in the recent advanced assisted reproductive technology (ART) era. A novel technique involving vasoepididymostomy with epididymal tubular invagination has been reported. We attempted to define the results of this method and to compare them with the conventional end‐to‐side technique in patients with suspected epididymal obstruction and no previous history of vasectomy.

Methods and Results: Eight eligible triangulation end‐to‐side vasoepididymostomy procedures performed on five azoospermic patients exhibiting either unilateral or bilateral epididymal obstruction are described. The overall patency rate following operation was 100% (five of five). Two pregnancies were achieved by natural intercourse and one was accomplished via artificial insemination. A single pregnancy was obtained with an intracytoplasmic sperm injection using frozen‐thawed sperm collected during the operation.

Conclusion: Vasoepididymostomy, using the triangulation technique for epididymal obstruction, resulted in an earlier patency in all patients. This method may afford advantages when compared with the conventional end‐to‐side approach; however, larger subject populations are required in order to assess further the efficacy of this procedure. In addition, long‐term follow up is necessary. (Reprod Med Biol 2003; 2: 101–104)
Erectile Dysfunction and Vascular Disease
Authors: Braatvedt G.
Published: September 2003

By M. Kirby. Oxford: Blackwell Publishing, 2003. 126 pp. $A57.15 (paperback). ISBN 1‐4051‐0753‐7
Management of the HIV‐infected patient
Authors: McCormack J.
Published: September 2003

Edited by S. Crowe, J. Hoy and J. Mills. London, Martin Dunitz, 2002. 618 pp. $A376.20 (hardback). ISBN 1‐901865‐28‐2.
Migraine: diagnosis and management
Authors: Goadsby P. J.
Published: September 2003

Abstract

Migraine is the most common form of disabling primary headache and affects approximately 12% of studied Caucasian populations. Non‐pharmacological management of migraine largely consists of lifestyle advice to help sufferers avoid situations in which attacks will be triggered. Preventive treatments for migraine should usually be considered on the basis of attack frequency, particularly its trend to change with time, and tract­ability to acute care. Acute care treatments for migraine can be divided into non‐specific treatments (general anal­gesics, such as aspirin or non‐steroidal anti‐­inflammatory drugs) and treatments relatively specific to migraine (ergotamine and the triptans). The triptans − sumatriptan, naratriptan, rizatriptan, zolmitriptan, almotriptan, eletriptan and frovatriptan − are potent serotonin, 5‐HT1B/1D, receptor agonists which represent a major advance in the treatment of acute migraine. Chronic daily headache in association with analgesic overuse is probably the major avoidable cause of headache disability in the developed world. (Intern Med J 2003; 33: 436−442)
Clinical and economic benefits of ramipril: an Australian analysis of the HOPE study
Authors: Smith M. G. , Neville A. M. , Middleton J. C.
Published: September 2003

Abstract

Background:  The Heart Outcomes Prevention Evaluation (HOPE) study has demonstrated that ramipril 10 mg/day for 5 years in an at‐risk population results in clinically and statistically significant reductions in the occurrence of cardiovascular death, myocardial infarction (MI), stroke and revascularization procedures. The likely impact of the intervention in Australia, in terms of the number of potential events avoided and the cost per life‐year saved, has previously not been determined.

Aims:  To assess the clinical and economic impacts of the use of daily ramipril in the Australian at‐risk popu­lation from the perspective of the public health‐care budget.

Methods: The clinical benefits were calculated from endpoints used in the trial, which were converted to the ‘number needed to treat’. These were then applied to the at‐risk population, which was determined nationally from the relevant Australian statistics. The result of this calculation is the potential number of events avoided in Australia.

The economic benefits were established by undertaking an incremental cost‐effectiveness analysis. The economic model considered the clinical benefits and the costs (and cost offsets) arising from ramipril 10 mg/day therapy for 5 years. Life‐years saved was determined by calculating the difference in total years survived between the ramipril and control arms of the study. Net costs divided by life‐years saved is the cost per life‐year saved, and this is reported in Australian dollars as the incremental cost effectiveness.

Results:  The clinical benefits over a 5‐year period were expressed as the number of potential events avoided and comprised approximately: 9188 strokes; 14 658 MI; 14 317 revascularization procedures; and 12 534 cardiovascular‐related deaths, nationally. The incremental cost‐effectiveness analysis showed the estimated cost per life‐year saved to be $A17 214.

Conclusion:  The use of ramipril 10 mg/day over a 5‐year period in the at‐risk Australian population could prevent many thousands of cardiovascular events, including 12 534 cardiovascular‐related deaths. The cost per life‐year saved compares favourably to other health care interventions. (Intern Med J 2003; 33: 414−419)
Use of fluorodeoxyglucose positron emission tomography scans in patients with advanced germ cell tumour following chemotherapy: single‐centre experience with long‐term follow up*
Authors: Karapetis C. S. , Strickland A. H. , Yip D. , Steer C. , Harper P. G.
Published: September 2003

Abstract

Aims:  Fluorodeoxyglucose positron emission tomog­raphy (FDG‐PET) may detect residual or recurrent malignancy in patients with germ cell tumours (GCT) following chemotherapy. The objective of the present study was to evaluate the use of FDG‐PET in the setting of advanced GCT, and to determine the influence of FDG‐PET on subsequent patient management.

Methods:  A computerized search of the patient database of the Department of Medical Oncology, Guy's Hos­pital, London, United Kingdom, and a manual search of medical records, were conducted. All male patients with metastatic or extragonadal GCT treated with chemotherapy between July 1996 and June 1999 inclusive were identified. Data from patients that had a PET scan following chemotherapy were analysed. Reported PET scan findings were compared with subsequent clinical management and patient outcome.

Results:  A total of 30 patients with metastatic testicular GCT and three patients with extragonadal GCT were treated with chemotherapy. Of these, 15 patients (12 testicular; three extragonadal; 10 non‐seminoma; and five seminoma) were investigated following chemo­therapy with at least one FDG‐PET scan. Seven patients had two or more PET scans, and a total of 26 FDG‐PET scans was performed. The most frequent indication for PET scan was evaluation of a residual mass (11 patients). Three patients had an FDG‐PET to evaluate thymic prominence. Minimum follow up from first PET scan was 18 months. Three of 26 PET scans had false positive findings. Four PET scans yielded findings of equivocal significance with repeat PET scan recommended. Relapse of disease occurred in three patients; two of whom had normal previous PET scans and one had a previous equivocal result. PET had an impact on patient management in only one case where it ‘prompted’ surgical excision of a residual mass. Normal PET scans provided reassurance in patients with residual small masses but did not alter their subsequent ­management.

Conclusions:  A residual mass was the most common indication for PET. For the majority of patients PET did not have a discernible influence on clinical management. Oncologists should exercise caution in their interpretation of PET scan findings and guidelines for the appropriate use of PET in testicular cancer management need to be developed. Prospective trials are required to define the clinical role of PET in this setting. (Intern Med J 2003; 33: 427−435)
Snapshot of acute asthma: treatment and outcome of patients with acute asthma treated in Australian emergency departments
Authors: Kelly A.‐M. , Powell C. , Kerr D.
Published: September 2003

Abstract

Aims: To characterize presentations due to acute asthma at Australian emergency departments (ED), including their severity, treatment and disposition.

Methods: This prospective, observational study involved 38 departments of emergency medicine throughout ­Australia participating in the Snapshot of Asthma Study Group project 2000 and 2001. Data were collected for patients presenting with acute asthma between 21 August 2000 and 3 September 2000, and 20 August 2001 and 2 September 2001 and included demographics, severity classification, treatment and disposition.

Results: There were 1340 acute asthma presentations in the study periods. Of these presentations, 67% were for children aged <15 years. Asthma severity (according to the Australian National Asthma Guidelines classifi­cation) was ‘mild’ in 49% of cases; ‘moderate’ in 45% of cases; and ‘severe’ in 6% of cases. Treatment administered included: (i) salbutamol to 90%, (ii) ipratropium bromide to 59% and (iii) corticosteroids to 71%. Only six patients received aminophylline. Spacer use for sal­butamol was rare (1%) in adults and only moderate (43%) in children. Sixty‐five percent of patients were discharged home from the ED. Less than 1% of patients required ventilatory assistance, of which half was provided non‐invasively. One percent of patients were admitted to the intensive‐care unit or high‐dependency unit.

Conclusion: Overall adherence to treatment guidelines was good. There appears to be underuse of spacers and corticosteroids in some groups and overuse of ipra­tropium bromide. The majority of patients are treated and discharged from the ED. (Intern Med J 2003; 33: 406−413)
Long‐term outcome of antiandrogen monotherapy in advanced prostate carcinoma: 12‐year results of a phase II study
Authors: Serretta V. , Daricello G. , Dispensa N. , Allegro R. , Pavone C. , Pavone‐Macaluso M.
Published: September 2003

OBJECTIVE

To present the long‐term outcome of patients with locally advanced or metastatic prostate carcinoma treated by first‐line antiandrogen monotherapy.

PATIENTS AND METHODS

From 1983 to 1990, 41 patients with advanced prostate carcinoma were treated with flutamide monotherapy until progression or the appearance of toxicity. Twenty‐five patients (61%) had T3‐T4N0M0 and 16 (39%) T2–4N0–3M1 prostate carcinoma. Consensus criteria were adopted to evaluate the response. Plasma testosterone and sexual function were recorded for the first 3 years.

RESULTS

Flutamide was administered for up to 147 months; seven patients (17%) interrupted the treatment because of toxicity. There was an objective response in 17 (41%) patients; 20 (49%) had stable disease while four (10%) progressed. There were objective responses, lasting up to 150 months, in 82% of those with M0 and in 18% with M1 disease (P = 0.05). The median time to progression in patients with an objective response and stable disease was 45 and 16 months, respectively (P < 0.001). Thirty‐one patients (76%) died from prostate cancer and 10 (24%) from unrelated diseases. The median survival was 67 and 36 months in patients with an objective response and stable disease, respectively (P < 0.001). There was an improvement in performance status in 85% and reduction in bone pain in 83% of the patients; sexual activity was maintained in 63%.

CONCLUSION

Monotherapy with flutamide is well tolerated. Objective responses are more frequent in patients with locally advanced disease. Patients with an objective response within 6 months have a prolonged progression‐free and overall survival.
Surface modification to improve in vitro attachment and proliferation of human urinary tract cells
Authors: Marcovich R. , Seifman B. , Beduschi R. , Wolf J.S.
Published: September 2003

OBJECTIVE

To evaluate the attachment and proliferation of cultured human urinary tract cells to culture plates surface‐modified by photochemical immobilization of extracellular matrix (ECM) proteins.

MATERIALS AND METHODS

Human uroepithelial (UEC) and smooth muscle (SMC) cells were harvested from ureter and expanded in culture; 24‐well culture plates surface‐modified by photochemical covalent immobilization of ECM proteins were then seeded with UEC or SMC. To characterize cellular attachment, cells were incubated on surface‐modified plates for 30 and 90 min. For proliferation assays the cells were incubated for 3–12 days. Standard tissue culture plates with no surface modification and sham‐modified plates served as controls. Differential attachment and proliferation on the various surfaces were assessed using analysis of variance with Fisher's posthoc test for multiple comparisons.

RESULTS

Attachment at 30 and 90 min of both UEC and SMC on plates surface‐modified with ECM proteins was significantly greater than in control plates. Surface‐modification with collagen resulted in significantly greater cellular attachment than with either laminin or fibronectin. UEC proliferation was also significantly greater than in control plates by surface‐modification with collagen and fibronectin, but not with laminin. SMC proliferation was significantly better after surface modification than on sham‐ modified plates, but was no better than standard plates.

CONCLUSIONS

Covalent photochemical immobilization of ECM proteins to potential growth surfaces enhances the attachment of cultured UEC and SMC and the proliferation of UEC. This technique might be useful in modifying surface properties of synthetic polymer‐based materials in a controlled and defined manner, giving them the capacity to promote and sustain the growth of urinary tract cells. This may lead to development of alternative methods of tissue engineering in the urinary tract.
Bladder wall tension during physiological voiding and in patients with an unstable detrusor or bladder outlet obstruction
Authors: Bross S. , Braun P.M. , Michel M.S. , Juenemann K.P. , Alken P.
Published: September 2003

OBJECTIVE

To develop and evaluate a new clinical method for measuring bladder wall tension (BWT) on detrusor contraction during physiological voiding and under pathological conditions, as in experimental trials during subvesical obstruction the ability to generate pressure increases, whereas the contractile force per cross‐sectional area of detrusor muscle decreases.

PATIENTS AND METHODS

In all, 24 patients were divided into three equal groups: group 1 (mean age 58, sd 8.6 years) comprised men with bladder outlet obstruction in accordance with the Abrams‐Griffiths nomogram; group 2 (four men and four women, 56, sd 7.2 years) had detrusor instability; and group 3 (54, sd 9.6 years) had normal bladder emptying. BWT, as the detrusor force per cross‐sectional area of bladder tissue (in N/cm2), was calculated after a urodynamic evaluation and ultrasonographic estimate of bladder wall thickness.

RESULTS

In all patients it was possible to measure BWT; the mean (sd) maximum BWT in group 1 was 9.8 (3.9) N/cm2, in group 2 during bladder instability was 11.7 (2.6) N/cm2 and in group 3 was 2.8 (0.5) N/cm2.

CONCLUSIONS

Estimating BWT in humans is possible by combining a urodynamic evaluation with an ultrasonographic estimate of bladder wall thickness. Further clinical research should elucidate the clinical relevance of BWT under comparable conditions.