bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian Dysgerminoma with Massive Metastases to Para-Aortic Lymph Nodes
Authors: Takemori Masayuki , Ichimura Takaya , Nishimura Ryuichiro , Hasegawa Kazuo
Published: April 2003

We report on a 15-year-old female with left ovarian dysgerminoma accompanied by massive swelling of the para-aortic lymph nodes which was clearly demonstrated by preoperative magnetic resonance imaging (MRI). Metastasis to the para-aortic lymph nodes from dysgerminoma was confirmed by biopsies obtained during surgery. No study has previously reported dysgerminoma with massive para-aortic lymph node metastases clearly demonstrated by MRI. These preoperative MRI findings are presented here. The patient received six cycles of cisplatin-based combination chemotherapy with the BEP regimen (bleomycin, etoposide and cisplatin) after conservative surgery, and no residual para-aortic lymph nodes were detected by MRI or CT after the chemotherapy.
Osteochondroma of the Pubic Symphysis Associated with Sexual Disturbance
Authors: Hoshimoto Kazunori , Mitsuya Kazuhiro , Ohkura Takeyoshi
Published: April 2003

Osteochondroma of the pubic symphysis is a rare benign skeletal tumor. We report here a case of an osteochondroma of the pubic symphysis associated with a sexual disturbance, where a computed tomography scan clearly showed a tumor lesion of the pubic symphysis. The case is reported not only because of its rarity but also because it is important that gynecologists should bear this disease in mind, since a patient with this tumor may not visit an orthopedist but a gynecologist.
Altered Thiol Status in Preeclampsia
Authors: Kharb Simmi
Published: April 2003

Thirty preeclamptic, 30 normotensive pregnant and 25 healthy nonpregnant women were analyzed with regard to the antioxidant system (thiols and superoxide dismutase, SOD). In preeclampsia both plasma and lysate thiol levels were significantly lower compared to controls (p < 0.001). SOD levels were higher in normotensive pregnant women, but were lower in preeclamptic compared to nonpregnant women. This finding of antioxidant changes in the red blood cell suggests that red cell dysfunction is fundamental in the development of preeclampsia, and similar alterations in the balance of the thiol could be present across the endothelial cell membrane.
Sublingual Isosorbide Dinitrate in the Acute Control of Hypertension in Patients with Severe Preeclampsia
Authors: Martínez-Abundis Esperanza , González-Ortiz Manuel , Hernández-Salazar Francisco , Huerta-J-Lucas María Teresa
Published: April 2003

The objective of this study was to evaluate the effectiveness of sublingual isosorbide dinitrate (ID) in the acute control of hypertension in patients with severe preeclampsia. A randomized, double-blind clinical trial with a preinclusion period of response to hydration and rest was performed in 60 patients with severe preeclampsia. The treatment group (30 patients) received 5 mg of sublingual ID, a dose that could be repeated on a second occasion. The control group consisted of 30 patients who received placebo. Both groups continued with rest and hydration during the study. Maternal blood pressure and fetal heart rate were measured in all patients every 10 min until 1 h was completed. Treatment was considered effective when the diastolic blood pressure could be reduced to between 80 and 100 mm Hg. ID was effective in 56.6% of the patients in the first 10 min after its administration and in 96.6% from 40 to 60 min. In the treatment group the systolic and diastolic blood pressures dropped gradually from 171 ± 13 and 113 ± 8 mm Hg, respectively, to 136 ± 14 and 87 ± 9 mm Hg. In the placebo group, blood pressure was not reduced. There was no significant difference in fetal heart rate between both groups throughout the study. In conclusion, ID was shown to be effective in the acute control of hypertension in patients with severe preeclampsia, where high blood pressure persists after a period of rest and hydration.
Apoptosis in Human Term Placenta
Authors: Thiet Mari-Paule , Suwanvanichkij Voravit , Hasselblatt Kathleen , Yeh John
Published: April 2003

The objective of this study was to examine placentas after delivery from normal, healthy patients at term gestation. The placentas were from elective cesarean sections (n = 10, prior to the onset of labor) and spontaneous vaginal delivery (n = 10, after labor). We found that deoxyribonucleic acid laddering was present in all placentas and consistent with the pattern found in tissues that undergo apoptosis. Paraffin-embedded sections of placental villi stained by the in situ terminal deoxynucleotidyl transferase mediated biotinylated dUTP nick end labeling method revealed positive apoptotic nuclei in the placental villi. Reverse-transcriptase polymerase chain reaction demonstrated expression of messenger RNA for testosterone-repressed prostate message 2 and B cell lymphoma/leukemia-2 in the placenta. Our data demonstrate that apoptosis occurs in human term placenta.
A Severe Case of Myasthenia gravis during Pregnancy
Authors: Pijnenborg J.M.A. , Hansen E.C.M. , Brölmann H.A.M. , Oei S.G. , Andriessen P. , Dellemijn P.L.D.
Published: April 2003

Myasthenia gravis is characterised by muscle weakness and fatigability, particularly of the facial and extremity muscles, deteriorating during the day. During pregnancy, myasthenia gravis is rare and the course of illness is unpredictable. The present case illustrates that first diagnosed during pregnancy, recurrent exacerbations can appear and lead to life-threatening situations.
Coasting May Reduce the Severity of the Ovarian Hyperstimulation Syndrome in Patients with Polycystic Ovary Syndrome
Authors: Ohata Yorie , Harada Tasuku , Ito Masayuki , Yoshida Souichi , Iwabe Tomio , Terakawa Naoki
Published: April 2003

The aim of our study was to determine the efficacy of postponing administration of human chorionic gonadotropin while continuing daily gonadotropin-releasing hormone agonist therapy (‘coasting’) to prevent the occurrence of severe ovarian hyperstimulation syndrome (OHSS) for patients with polycystic ovary (PCO) syndrome. Five patients with PCO who had been hospitalized due to severe OHSS in previous in vitro fertilization and embryo transfer or intrauterine insemination cycles at the Tottori University Hospital were included in the study. The rates of mature oocytes and fertilization were comparable between the cycles. A singleton pregnancy was achieved in a patient during the coasting cycle, and none of the women developed severe OHSS in coasting cycles. The results suggest that coasting may be an alternative method for reducing the severity of OHSS in patients with PCO.
Primary Peritoneal Carcinoma: A Report of Twelve Cases and a Review of the Literature
Authors: Cormio Gennaro , Di Vagno Giovanni , Di Gesù Giuseppe , Mastroianni Maria , Melilli Giovanni A. , Vimercati Antonella , Putignano Giuseppe , Loverro Giuseppe , Selvaggi Luigi
Published: April 2003

Primary peritoneal carcinoma (PPC) is rare tumor histologically identical to epithelial ovarian carcinoma (EOC); it is differentiated from EOC based on the extent of gross ovarian involvement and microscopic invasion of the cortex. We report 12 cases of PPC which were diagnosed in our Department during a 9-year period. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed in 9 patients, while 3 underwent only explorative laparotomy with bilateral salpingo-oophorectomy. All patients were treated with postoperative platinum-based chemotherapy. After a median follow-up of 42 months, only 5 patients are alive without disease. PPC is a rare tumor currently managed in the same way as ovarian cancer. Primary debulking surgery and chemotherapy represent the cornerstones of treatment. Considering the limited number of patients with PPC, no definitive conclusion can be drawn concerning the prognostic factors for survival.
Analysis of TH1 and TH2 Cells by Intracellular Cytokine Detection with Flow Cytometry in Patients with Ovarian Cancer
Authors: Aoki Yoichi , Tsuneki Ikunosuke , Sasaki Masaru , Watanabe Minoru , Sato Takaaki , Aida Hiroshi , Tanaka Kenichi
Published: April 2003

Objective: Our aim is to assess the immune status of patients with ovarian cancer by analyzing the ratio of T helper type 1 (TH1) to T helper type 2 (TH2) populations in peripheral blood lymphocytes (PBL). Methods: We examined TH1/TH2 ratios in PBL obtained from 21 ovarian cancer patients who had just received postoperative chemotherapy, by detecting the intracellular IFN-γ and IL-4 production with 3-color flow cytometry. Additionally, we evaluated the influence of a granulocyte-colony stimulating factor (G-CSF) injection on TH1 and TH2 populations for a rescue of granulocytopenia due to the chemotherapy. Results: We could not find any significant difference of the TH1/TH2 ratios in terms of age, International Federation of Gynecology and Obstetrics (FIGO) clinical stage and clinical tumor status. As for the clinical tumor status, however, the patients with residual cancer had a higher TH1/TH2 ratio, though it was not statistically significant (p = 0.15). Anticancer chemotherapy is also considered to lead to the immunosuppressive state of the patients. TH1 and TH2 populations of PBL in the patients during chemotherapy showed an unfavorable imbalance that was shifted from TH1 to TH2 10 days after anticancer drug administration (p = 0.049). G-CSF administration, on the other hand, was likely to induce a cell population shift from TH2 to TH1 assessed by the intracellular cytokine assay (p = 0.051), and never induced an unfavorable imbalance from TH1 to TH2 in the T cell population by a 1-day injection of G-CSF. Conclusion: Together, these data indicate that the TH1/TH2 ratio analyzed by intracellular cytokine flow cytometry seems to be a good indicator to assess the immune status in cancer.
Effect of Acupuncture Treatment on Uterine Motility and Cyclooxygenase-2 Expression in Pregnant Rats
Authors: Kim Jeong-sang , Shin Ki Hyoung , Na Chang Su
Published: April 2003

As the pregnancy stage advances, prostaglandin (PG) concentrations increase in the uterus, being responsible for the increased uterus contractility during labor. Therefore, regulating the concentration of the PGs in the uterus is important for controlling preterm delivery. In oriental medicine traditionally, an acupuncture of LI-4 controls for the function and motility of the uterus. In this study, acupuncture treatment on the LI-4 acupoint in nonpregnant and pregnant rats was evaluated for its efficacy in the expression of COX-2 enzyme and uterus motility. Whether the rats were pregnant or not, immunohistochemical localization of the COX-2 enzyme was primarily found in the uterine endometrium with weak localization in the uterine myometrium. The level of expression in these two locations was intensified by pregnancy but reduced by the LI-4 acupuncture. The infusion of PGF2α in pregnant rats caused and increased COX-2 expression in the myometrium while it caused a decreased expression in the endometrium. The uterus motility monitored during the LI-4 acupuncture reduced to 67.0% in nonpregnant rats, and to 75.0% in pregnant rats. PGF2α infusion in pregnant rats increased uterine motility to 117.3%. The significant reduction in uterus motility in pregnant rats supports the role of LI-4 acupuncture in inhibiting the expression of COX-2 enzyme that can be used to regulate complicated preterm labor.
F1α: A Novel Mucin Antigen Associated with Gastric Carcinogenesis
Authors: Yamashita Yoshito , Chung Yong-Suk , Sawada Tetsuji , Horie Ryuichi , Saito Takashi , Murayama Keiichi , Kannagi Reiji , Sowa Michio
Published: April 2003

In a previous study, we obtained a novel monoclonal antibody (F1α-75) directed against a synthetic mucin antigen termed F1α, and demonstrated that this antigen was expressed in a high percentage (80.2%; 89/111) of gastric carcinomas. In the present study, we compared the expression of F1α with that of sialyl-Tn antigen, a mucin antigen similar to F1α, in 54 human early gastric carcinomas, intestinal metaplasia and adenomatous polyps of the stomach to determine how differences in the expression of these antigens correlated with gastric carcinogenesis. The rate of expression of F1α in early gastric carcinoma tissues, 81.5%, was higher than that of sialyl-Tn antigen, 57.4%. No correlation was found between the rate of expression and histological type, depth of cancerous invasion or lymph node metastasis. Sialyl-Tn antigen was extensively expressed in 77.5% of specimens of complete intestinal metaplasia and in 78.6% of those of incomplete intestinal metaplasia; however, the expression of F1α in those specimens was rare and sporadic, with rates of only 25.0 and 27.7%, respectively. In adenomatous polyps, the rate of expression of F1α is 6.25% and that of sialyl-Tn antigen is 43.8%. Our findings indicate that F1α is a more specific antigen for gastric cancer than sialyl-Tn antigen, and that F1α is an antigen associated with carcinogenesis of the stomach.
Adjuvant Chemotherapy with Oral Tegaful and Uracil for Maxillary Sinus Carcinoma
Authors: Fujii Masato , Ohno Yoshihiro , Tokumaru Yutaka , Imanishi Yorihisa , Kanke Minoru , Kanzaki Jin , Inuyama Yukio
Published: April 2003

We have applied tegaful and uracil (UFT) treatment as adjuvant chemotherapy to patients after the completion of primary therapy. UFT was given per os at a dose of 300 or 400 mg/day for more than 1 year. A retrospective study was conducted on 15 patients, assessed as the UFT-treated group, and 24 patients assessed as the UFT-nontreated group. The 5-year survival rate in patients treated or not treated with UFT was 76.6 and 22.6%, respectively. Among those who underwent surgery in combination with other therapy, the 5-year survival rate was 74.1% with UFT and 27.3% without UFT. In patients receiving chemotherapy plus radiotherapy alone, the 5-year survival rate was 80.0% with UFT and 19.2% without UFT. In 23 patients with proven effects of neoadjuvant chemotherapy comprising 18 PR cases and 5 CR cases, a comparison was made between 10 patients treated with UFT and 13 patients not treated with UFT. As a result, the 5-year survival was 76.2 and 17.9%, respectively. In the patients with T3 disease, who occupied the majority, the 5-year survival rate was 71.4 and 23.8%, respectively. Adjuvant chemotherapy with UFT tends to show a substantial significant difference particularly in patients who were successfully treated with radiotherapy plus chemotherapy as the primary treatment. UFT was clearly shown to have a statistically significant effect, despite a small population. The findings of the present investigation point to the value of conducting further study to ascertain the effect of UFT by a randomized trial in a larger population.
Prognosis and Management Strategies of Lymphatic Neoplasias in the Elderly
Authors: Greil Richard
Published: April 2003

Lymphomas belong to the class of malignant diseases with the fastest increasing incidence. High-grade non-Hodgkin’s lymphomas (NHL) display a peak of incidence in the age group above 65. In the last few years, age has been recognized as a major risk factor for overall survival of high-grade NHL patients, and numerous attempts have been made to analyze the contribution of factors to the age-related worsening of prognosis in this disease, e.g. the biology of the disease on the one hand, and age-specific comorbidity or degree of cytotoxicity, reluctance in diagnosis and treatment and socioeconomic factors on the other. Furthermore, age-adapted treatment protocols have been designed and tested for their practicability and efficacy in the elderly. Very recently, large randomized prospective clinical trials have been carried out which support the idea that treatment with a curative intent is warranted even in the very elderly and that a successful attempt to cure requires the use of full-dose anthracycline-containing regimens closely similar to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). In addition, progress has been made in systematically defining maximally tolerated doses of the cytotoxic drugs and in specifically testing anthracyclines with reduced cardiotoxicity with an efficacy similar to that of doxorubicin, and further in investigating the advantage of applying hematopoietic growth factors and/or cardioprotective drugs in this older population. In limited stages of disease, three cycles of CHOP chemotherapy followed by involved field irradiation may be superior to radiotherapy and prolonged chemotherapy and may produce highly satisfying cure rates.
Paclitaxel in Cisplatin or Carboplatin-Pretreated Ovarian Cancer
Authors: Pectasides D. , Papadopoulou M. , Varthalitis J. , Mylonakis A. , Kostopoulou M. , Dimitriadis M. , Athanassiou A.
Published: April 2003

A phase II trial was conducted in order to assess the efficacy and toxicity of paclitaxel given at a dose of 175 mg/m2 in a 3-hour infusion every 3 weeks in patients with recurrent or cisplatin (CDDP) carboplatin-refractory ovarian cancer. Forty-two patients with a median age of 61 years (range 34–76 years) entered the study. Most patients had bulky disease. Thirty-three patients (78.5%) presented with stage III and IV diseases. Twenty-two patients (52.3%) had previously been treated with only 1 regimen and 20 patients (47.7%) with ≥2 regimens. The median treatment interval from the last previous therapy was 4.5 months (range 2–26 months). From 41 patients evaluable for response, 3 (7.3%) achieved a complete and 4 (9.8%) a partial response. All 3 complete and 2 out of the 4 partial responders had previously received ≥2 chemotherapeutic regimens. Grade 3–4 toxicities included granulocytopenia (35%), which was of short duration, neurotoxicity (9.75%) and alopecia (60.9%). Two patients with grade 4 neutropenia were hospitalized due to pneumonia, which was successfully treated by broad-spectrum antibiotics and administration of G-CSF. A severe hypersensitivity reaction occurred in 1 patient early during the first cycle, resulting in discontinuation of treatment. Median relapse-free survival was 6.9 months, median time to progression 6.2 months and median survival 13.2 months.In conclusion, paclitaxel given at a dose of 175 mg/m2 as a 3-hour infusion every 3 weeks appears to be an efficacious and well-tolerated treatment in patients with recurrent or CDDP/carboplatin-refractory ovarian cancer.
Correlation between Telomerase Activity and DNA Ploidy in Gastric Cancer
Authors: Okusa Yasushi , Shinomiya Nariyoshi , Ichikura Takashi , Mochizuki Hidetaka
Published: April 2003

Telomerase has been reported to be activated in most immortal cells and human cancers. In the present study, we assessed the correlation between telomerase activity and cellular DNA ploidy level in gastric cancer. Telomerase activity was determined semiquantitatively using the telomeric repeat amplification protocol assay, a polymerase-chain-reaction-based assay, in surgical specimens of primary tumors obtained from 36 patients with gastric cancer. No correlation was observed between telomerase activity and the proliferating cell nuclear antigen labeling index. In contrast, a positive linear correlation was observed between telomerase activity and the DNA index (r = 0.59; p < 0.01). Tumor cells with aneuploid patterns showed higher telomerase activity than those with diploid patterns (27.6 ± 5.8 vs. 5.8 ± 1.1%; p < 0.01). Telomerase activity of tumors with liver metastases was significantly higher than activity of those without metastases (34.5 ± 16.6 vs. 11.8 ± 2.4; p < 0.05). There was a trend toward a lower survival rate in 9 patients with a telomerase activity of 20% or higher compared to 27 patients with telomerase activity lower than 20%. These results suggest that the telomerase activity of gastric cancer tissue may reflect the malignant potential of the tumor.
Does Dexamethasone Enhance the Efficacy of Alizapride in Cis-Platinum-Induced Delayed Vomiting and Nausea?
Authors: Münstedt K. , Wunderlich I. , Blauth-Eckmeyer E. , Zygmunt M. , Vahrson H.
Published: April 2003

At the present time 5-HT3 antagonists in combination with corticosteroids represent the best prophylaxis and treatment of acute vomiting and nausea in highly emetogenic cancer chemotherapy. However, 24 h after chemotherapy 5-HT3 antagonists are no longer superior to benzamides for prevention of delayed symptoms. All recommendations for use of corticosteroids in delayed nausea and vomiting basically rely on one small study by Kris et al. [J Clin Oncol 1989;7:108–114]. Since the use of corticosteroids in cancer chemotherapy remains controversial, this single-blind, randomised, prospective trial was initiated to re-evaluate the benefits of corticosteroids during the days after chemotherapy. Thus patients treated for ovarian cancer received 5 mg tropisetron (Navoban®) plus 20 mg dexamethasone for the prevention of acute vomiting and nausea in cis-platinum-containing chemotherapy (50 mg). Twenty-four hours after the beginning of chemotherapy 49 patients were randomised to receive 3 × 100 mg alizapride (Vergentan®) plus a placebo medication (group A) and 47 patients to receive 3 × 100 mg alizapride plus 3 × 4 mg dexamethasone (group B) for 3 days depending on the incidence of acute vomiting beginning on day 2. The well-being of both groups was compared using objective and subjective parameters (Rotterdam Symptom Checklist). Major control of acute vomiting was achieved in 87.5% of the cases. The study was stopped after this interim analysis of 96 patients revealed no advantage of corticosteroids during the days after chemotherapy. Significant differences between both groups were detected only on a few days (day 6: objective nausea in favour of group A, day 4: objective vomiting in favour of group B, day 6: objective vomiting in favour of group A, day 3: constipation in favour of group A, days 4 and 5: difficulty concentrating in favour of group A, day 3: dry mouth in favour of group B). In contrast to acute nausea and vomiting the addition of corticosteroids is not beneficial in the prevention of delayed nausea and vomiting. Until better stretegies are available the best prophylaxis of delayed symptoms is the control of acute nausea and vomiting using 5-HT3 antagonists plus corticosteroids. The use of benzamides has to be considered efficacious in the prevention of delayed vomiting and nausea.
Pleural and Bone Marrow Metastasis from Supratentorial Oligoastrocytoma Grade III
Authors: Finsterer J. , Breiteneder S. , Mueller M.R. , Wogritsch C. , Vesely M. , Kleinert R. , Pendl G. , Mamoli B.
Published: April 2003

We report a 62-year-old man with symptomatic metastasis to the pleural cavity and the bone marrow from a supratentorial oligoastrocytoma grade III, 24 years after the initial symptoms. Before tumor dissemination, the patient underwent brain surgery four times in 5 years. Six months after the last treatment, extraneural dissemination to the right pleural cavity was discovered. Despite resection of the pleural metastasis, local and distant spread to the bone marrow developed. The patient died 5 months after the occurrence of extraneural tumor metastasis. It is speculated that repeated brain surgery and extended survival may promote extraneural dissemination of supratentorial oligoastrocytoma grade III.
Strontium-89 Chloride in the Treatment of Bone Metastases from Breast Cancer
Authors: Baziotis N. , Yakoumakis E. , Zissimopoulos A. , Geronicola-Trapali X. , Malamitsi J. , Proukakis Ch.
Published: April 2003

Sixty-four patients with painful metastatic breast cancer in bone were treated with 2 MBq/kg of strontium-89 chloride as a single intravenous injection. Patients were followed with records of medication, hematology parameters, serial bone and Sr-89 bremsstrahlung images and with a point pain score scale (10–0). The response was assessed during a 6-month period of follow-up. Fifty-two of 64 patients (81%) showed at least a moderate improvement. Eighteen out of the 52 responders showed a dramatic decrease in bone pain (35%), 21 (40%) presented a satisfactory response and in 13 cases (25%) the response was moderate. Only 12 patients (19%) from the whole group did not feel any improvement on pain palliation. A statistically significant decrease of pretreatment levels of platelets and leukocyte counts was observed after 4–6 weeks of therapy in 50 (70%) patients. Although most patients showed no change in their bone scans after 3 months of treatment, an obvious improvement was observed in 3 of them. Furthermore no additional painful metastases on their bone scintigraphic images were observed. The selective strontium-89 local uptake in metastatic sites was also confirmed directly by bremsstrahlung scans which were absolutely comparable to the respective 99mTc bone scans. Precautions have been taken against Sr-89 contamination from the patients’ blood or excretions.
A Case Control Study on Risk Factors Involved in Inflammatory Breast Recurrence afterBreast-Conserving Surgery
Authors: Nishimura Reiki , Koyama Hiroki , Kasumi Fujio , Takashima Shigemitsu , Kobayashi Shunzo , Komaki Kansei , Ohkawa Tomohiko , Shin Eisei , Kodama Hiroshi , Fukutomi Takashi , Nishi Tsunehiro , Sonoo Hiroshi , Sano Sohmei , Kimishima Izo , Nakaue Kazuhiko , Nakamura Seigo , Kusama Mikihiro , Okumura Kenzo
Published: April 2003

Recurrence that poses the biggest problem after breast-conserving surgery is local recurrence. Particularly, in the case of inflammatory breast recurrence which is rare but has a specific pathologic nature, it is important to elucidate the pathology and risk factors and to consider appropriate countermeasures. In the present study, we classified 133 cases of recurrence following breast-conserving surgery, collected from 18 key hospitals/institutes in Japan. Recurrence types were divided into three groups, namely, inflammatory breast recurrence, noninflammatory breast recurrence and distant metastasis only, and the risk factors involved in recurrence were investigated by the case control study allotting 2 controls to each case. The study population consisted of 9 cases of the inflammatory type, 64 cases of the noninflammatory type and 60 cases of distant metastasis. The significant risk factor for inflammatory breast recurrence was positive lymph node metastasis, which was significantly more frequent in lymphatic invasion-positive cases unlike in the distant metastasis group. The positive surgical margin and nonradiation therapy which have been shown to be significant risk factors for noninflammatory breast recurrence were entirely unrelated with inflammatory breast recurrence. In addition, the inflammatory-type recurrence time was as short as about 12 months irrespective of whether radiation therapy was performed or not. The inflammatory type was accompanied with local wide extension (cancerous embolus of the dermal lymphatic vessels), and distant metastasis (lymphangitis carcinomatosa) at the time of recurrence, and further surgery was impossible in most cases, with a significantly poorer prognosis than the other recurrence types. These findings suggest that this recurrence corresponds to the so-called ‘occult’ case of primary inflammatory breast carcinoma. We think it important to predict this recurrence by close pathological examination, particularly in patients with lymph node metastasis, and to consider appropriate measures.
Clinical Significance of Combined Immunohistochemical Detection of CD44v and Sialyl Lex Expression for Colorectal Cancer Patients Undergoing Curative Resection
Authors: Yamaguchi Akio , Goi Takanori , Seki Kenichiro , Ohtaki Norio , Maehara Masanori , Kobayashi Ttaizo , Niimoto Syuichi , Katayama Kanji , Hirose Kkazuo , Nakagawara Gizo , Matsukawa Shigeru
Published: April 2003

To evaluate their prognostic value, the expressions of CD44v and sialyl LeX (SLX) in colorectal cancers were studied immunohistochemically. Tissue specimens were reacted with monoclonal antibodies (mAb) CD44-1V and CSLEX-1. Of the 145 colorectal cancer patients undergoing curative resection, 59 (40.7%) were positive for mAb CD44-1V, and 40 (27.6%) were positive for mAb CSLEX-1. There was a significant correlation between the combined expression of SLX and CD44v8–10 and lymph node metastasis. The patients with tumors negative for CD44v8–10 and SLX had the most favorable prognoses. Conversely, the patients with tumors positive for both CD44v8–10 and SLX had a high recurrence rate and the poorest prognoses. In a multivariate analysis using the Cox regression model, the combined expression of SLX and CD44v8–10 emerged as an independent prognostic indicator. These results suggested that the combined expression of CD44v8–10 and SLX may be a biologic marker of prognostic significance.
Clinical Evaluation of Pancreatitis-Associated Protein as a Serum Marker of Hepatocellular Carcinoma: Comparison with α-Fetoprotein
Authors: Montalto G. , Iovanna J.L. , Soresi M. , Dusetti N. , Carroccio A. , Barthelemy-Bialas S. , Cartabellotta A. , Dagorn J.C.
Published: April 2003

This study evaluated the significance of serum pancreatitis-associated protein (PAP) assay, as a marker of hepatocellular carcinoma (HCC), in comparison and combined with α-fetoprotein (AFP) assay. Sixty-five patients with HCC, 59 with liver cirrhosis (LC) and 68 asymptomatic controls (C) were studied. PAP and AFP values significantly increased from C to LC and HCC group (p < 0.0001). The area under receiver-operating characteristic (ROC) curve for the two markers was not statistically different. At 100% specificity, ROC analysis gave a cut-off level for AFP of 166 IU/l with 40% sensitivity, and a cut-off level of 240 µg/l for PAP with 23% sensitivity. Diagnostic accuracy of combined AFP and PAP assay was significantly higher than AFP alone. Sensitivity according to tumor size also improved using the combined assay, especially for tumors <5 cm. Stepwise logistic regression indicated that AFP, but not PAP, was associated with an increased risk of developing HCC. These data confirm that PAP production is increased only in some cases of HCC and that the combined PAP and AFP assays do not significantly improve specificity over AFP assay alone. Consequently, PAP assay can only be recommended in cases of justified suspicion of HCC with negative AFP.
Italian Guidelines for the Management of Infectious Complications in Pediatric Oncology: Empirical Antimicrobial Therapy of Febrile Neutropenia
Authors: Viscoli C. , Castagnola E. , Caniggia M. , De Sio L. , Garaventa A. , Giacchino M. , Indolfi P. , Izzi G.C. , Manzoni P. , Rossi M.R. , Santoro N. , Zanazzo G.A. , Masera G.
Published: April 2003

The Italian Association for Paediatric Haematology and Oncology prepared a guideline document aimed at unifying and rationalising as much as possible the management of febrile neutropenia in children with cancer, because of the potential impact of these procedures on hospital costs and on the development of antibiotic resistance. Before starting anti-infective therapy, at least 2 blood cultures, a throat swab, urine-culture, and cultures from any suspected infected site, should be performed. Routine chest X-rays at onset of febrile neutropenia are probably not necessary, in absence of respiratory signs. At the present time, the safer option probably remains the combination of a beta-lactam and an aminoglycoside, and treating febrile neutropenia outside of hospital should be considered an investigational approach. The choice of the most appropriated regimen for each institution should be based also on the local bacteriological statistics and patterns of bacterial resistance. Antibiotic toxicity and cost should be other important factors. Every subsequent addition or substitution of antibiotics should be based on objective signs of clinical deterioration. The only accepted empirical modification is empirical antifungal therapy, while the empirical addition of a glycopeptide antibiotic cannot be recommended.
Immunohistochemical Investigation of Thymidylate Synthase in Cervical Cancer
Authors: Suzuki Mitsuaki , Okabe Hiroyuki , Tsukagoshi Shizuka , Kawai Toshiro , Fukushima Masakazu , Sato Ikuo
Published: April 2003

We prepared a polyclonal antibody against recombinant human thymidylate synthase (TS) to evaluate its use in immunohistochemical analysis. Formalin-fixed, paraffin-embedded sections of specimens of cervical tissue were prepared from 35 patients with cervical cancer. The TS immunoreactivity was studied by employing the peroxidase-labeled antibody method with our prepared antibody. At the same time, the TS activity was determined with the 5-fluoro-2′-deoxyuridylate (FdUMP)-TS-binding assay in fresh-frozen specimens of these cervical cancers. We observed a positive correlation (r = 0.658) between the degree of TS immunoreactivity and the TS activity in the binding assay of 9 patients with grade 4 (strongly positive) TS immunoreactivity, while 7 patients (78%) exhibited a TS activity of 5 pmol/g tissue or greater. Nine patients with a TS immunoreactivity of grade 1 (negative to weakly positive) showed a TS activity <5 pmol/g tissue. The difference between the two groups was statistically significant (p < 0.01). TS expression was easily detected by the immunohistochemical technique which will allow the assessment of the relationship between TS activity and patient outcome.
Tumor Angiogenesis as a Prognostic Predictor in Colorectal Carcinoma with Special Reference to Mode of Metastasis and Recurrence
Authors: Choi Hong Jo , Hyun Moon Soo , Jung Ghap Joong , Kim Sang Soon , Hong Sook Hee
Published: April 2003

Tumor angiogenesis has proved to be a useful prognostic determinant for patients with various solid tumors. In this study, we investigated the quantitative expression of angiogenesis in colorectal carcinoma to determine how angiogenesis correlates with clinicopathologic factors and prognosis. One hundred twenty-seven specimens resected from patients with primary colorectal carcinoma were investigated immunohistochemically using a polyclonal antibody against factor-VIII-related antigen, and areas with the highest vascular density at the invasive tumor margin were counted at 200 times magnification. The microvessel count, defined as angiogenesis density (AD), became significantly higher with increase in histologic grade (p = 0.02) and Dukes stage (p = 0.001). AD was also significantly higher in patients with lymph node metastasis (p = 0.005), lymphatic invasion (p = 0.042), vascular invasion (p < 0.001), and liver metastasis (p = 0.0004) than in those without. In addition, patients with synchronous distant hematogenous metastasis in stage D disease showed significantly higher AD than patients with nonhematogenous metastasis (p = 0.006). When 27 cases of disease recurrence after surgical resection with curative intent were stratified according to mode of spread, AD in cases with a hematogenous pattern of relapse proved to be significantly higher than in cases with nonhematogenous spread (p < 0.001). No significant differences were, however, found in AD when they were subdivided as to operative nodal status (p = 0.39 and 0.08 in the node-negative and the node-positive group, respectively). Multivariate analysis indicated that AD was an independent prognostic factor (p = 0.0004) in colorectal carcinoma. Quantitative evaluation of tumor angiogenesis at the invasive tumor margin is suggested to be a good prognostic indicator and a useful predictor for hematogenous spread and recurrence in patients with colorectal carcinoma.
Overexpression of Transforming Growth Factor-β1 in Scirrhous Carcinoma of the Stomach Correlates with Decreased Survival
Authors: Kinugasa Shoichi , Abe Shun’ichi , Tachibana Mitsuo , Hishikawa Yoshitaka , Yoshimura Hiroshi , Monden Naomi , Dhar Dipok Kumar , Nagasue Naofumi , Nagaoka Saburo
Published: April 2003

A retrospective study of 50 patients with scirrhous carcinoma of the stomach who had undergone surgery was performed to elucidate whether immunohistochemical overexpression of transforming growth factor-β1 (TGF-β1) could predict the patients’ survival. To evaluate the proliferative activity of the tumor, the proliferating cell nuclear antigen (PCNA) index was used. Expression of TGF-β1 was low in 27 patients and high in 23. Clinicopathological characteristics were not significantly different between the two groups with high and low TGF-β1 expression. Tumors with higher TGF-β1 expression had higher PCNA indices (p = 0.0467, unpaired Student’s t test). The 5-year survival rate was 40.4% for the low TGF-β1 group and 28.7% for the high TGF-β1 group (p = 0.0388, log rank test). By multivariate analysis, pT, residual tumor, and TGF-β1 were the independent prognostic factors. These results suggest that immunohistochemical expression of TGF-β1 is one of the useful predictors for estimating the patients’ survival in scirrhous carcinoma of the stomach particularly of the T3 and T4 stages.
Frequent Amplification of C-erbB2 (HER-2/Neu) Oncogene in Cervical Carcinoma as Detected by Non-Fluorescence in situ Hybridization Technique on Paraffin Sections
Authors: Sharma A. , Pratap M. , Sawhney V. Malhotra , Khan I.U. , Bhambhani S. , Mitra A.B.
Published: April 2003

Sixty primary untreated squamous cell carcinomas were studied for C-erbB2 gene amplification by non-fluorescence in situ hybridization technique. Amplified tumour cells showed intranuclear dark brown, often paired signals under light microscopy. Twenty-two out of 60 tumours (36.6%) showed signs of amplification of different degree (+ to ++++). Considerable heterogeneity of C-erbB2 amplification per cell was seen within each amplified tumour. The proportion of amplified cells ranged between 10 and 90% in these tumours. The arrangement of C-erbB2 in clusters in most amplified tumours suggests that C-erbB2 amplification occurs intrachromosomally. No significant difference in the frequency of amplification was observed according to clinical stage or the histological patterns of the tumours. The results of the present study showed frequent amplification of C-erbB2 in cervical carcinoma on paraffin sections. This technique was found to be more sensitive than the Southern blot technique which could detect amplification in 14% of the tumours of the same cohort.
Hemolytic-Uremic Syndrome during Therapy with Estramustine Phosphate for Advanced Prostatic Cancer
Authors: Tassinari Davide , Sartori Sergio , Panzini Ilaria , Ravaioli Alberto , Iorio Domenico
Published: April 2003

3 weeks after commencing treatment with estramustine phosphate, typical manifestations of hemolytic-uremic syndrome occurred in a 66-year-old patient with prostate cancer. Urinary tract obstructions were excluded and no renal damage could be identified. An improvement in renal function was achieved by stopping estramustine phosphate and infusing adequate amounts of fluids and electrolytes. Anemia and thrombocytopenia also progressively improved after the discontinuation of chemotherapy. Nausea and vomiting, hepatotoxicity, impotence, reduced libido and hypercalcemia are major side effects of estramustine phosphate, and would be difficult to explain our observations without considering the role played by estramustine phosphate. Our observations suggest that estramustine phosphate might play either a direct role or produce a side effect within the context of latent paraneoplastic syndrome. The improvement in renal function which occurred when treatment stopped might confirm our hypothesis.
Gross Pathologic Types of Hepatocellular Carcinoma in Italy
Authors: Stroffolini Tommaso , Andreone Pietro , Andriulli Angelo , Ascione Antonio , Craxì Antonio , Chiaramonte Maria , Galante Domenico , Manghisi Onofrio Giuseppe , Mazzanti Roberto , Medaglia Cinzia , Pilleri Giampaolo , Rapaccini GianLudovico , Albanese Maddalena , Taliani Gloria , Tosti MariaElena , Villa Erica , Gasbarrini Giovanni
Published: April 2003

The prevalence and independent predictors of the different macroscopic types of hepatocellular carcinoma (HCC) were assessed in 1,073 unselected patients of 14 hospitals in Italy from May 1996 to May 1997. Solitary HCC was the most common cancer type (44.6%), followed by multinodular (44.2%), diffuse (8.4%) and massive (2.8%) types. After adjustment for the influence of confounders by multiple logistic regression analysis, Child-Pugh grades B and C were found to be independent predictors of multinodular (odds ratio, OR, 2.0; 95% confidence interval (CI) = 1.5–2.6) and diffuse (OR 2.6; 95% CI = 1.6–4.4) HCC types. These findings indicate that the majority of HCC cases are not detected at a potentially treatable stage. Delayed detection of HCC is associated with a higher likelihood of the multinodular or diffuse gross pathologic type.
Carboplatin, Methotrexate and 5-Fluorouracil in Combination with Medroxyprogesterone Acetate (JMF-M) in the Treatment of Advanced or Recurrent Endometrial Carcinoma: A Hellenic Cooperative Oncology Group Study
Authors: Bafaloukos D. , Aravantinos G. , Samonis G. , Katsifis G. , Bakoyiannis C. , Skarlos D. , Kosmidis P.
Published: April 2003

Twenty-three patients with advanced or recurrent endometrial carcinoma entered a prospective study of chemotherapy which consisted of carboplatin (300 mg/m2), methotrexate (30 mg/m2), and 5-fluoruracil (500 mg/m2) given on day 1, in a 3-weekly schedule, in combination with medroxyprogesterone acetate (MPA): 300 mg daily, p.o., until progression (JMF-M regimen). None had received prior chemotherapy and/or hormonotherapy for metastatic disease. Ten patients had received radiotherapy. Response to treatment was evaluated every two courses. Objective response was seen in 17 of the 23 patients (74%, 95% confidence interval = 52–90%), with 2 long-lasting complete responses (9%). The median response duration was 10+ months (3–45+). The median survival was 16+ months (2–45+). The 2 complete responders, the first in the lung and the second in groin nodes, are without evidence or recurrence after 32 and 45 months, respectively. The regimen was given on an outpatient basis and was well tolerated. The major toxic effects were myelosuppression (less than 14% leukopenia, anemia and thrombocytopenia). The MPA-related side effects were: weight gain (22%), hypertension (17%) and thromboplebitis (17%). In 2 patients, consolidation treatment with MPA was discontinued because of thromboplebitis. In conclusion, the JMF-M regimen is highly active with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.
Prediction of Response to 5′-Deoxy- 5-Fluorouridine (5′-DFUR) in Patients with Inoperable Advanced Gastric Cancer by Immunostaining of Thymidine Phosphorylase/Platelet-Derived Endothelial Cell Growth Factor
Authors: Koizumi Wasaburo , Saigenji Katsunori , Nakamaru Naomi , Okayasu Isao , Kurihara Minoru
Published: April 2003

Background: No reliable method is available for predicting the response to chemotherapy in patients with gastric cancer. The anticancer drug 5′-deoxy-5-fluorouridine (5′-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase). We studied the relation between the expression of dThdPase in tumor tissue and the response to treatment with 5′-DFUR to determine if this enzyme can be used to predict the response to chemotherapy. Methods and Materials: We performed endoscopic biopsy and studied the expression of dThdPase by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with inoperable advanced gastric carcinomas before they received multiple-drug chemotherapy, including 5′-DFUR. The relation between the expression of dThdPase and the response to chemotherapy was studied. We also studied the characteristics of positive cells against anti-dThdPase monoclonal antibody. Results: The response rate among patients whose tumors were positive for dThdPase expression (56.8%, 21/37) was higher than that among patients whose tumors were negative for dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing dThdPase were sporadically seen surrounding cancer nests in some patients. Multiple-antibody immunostaining suggested that these spindle-shaped cells were perivascular mesenchymal cells. The response rate was 82.4% (14/17) among patients with spindle-shaped cells strongly positive for dThdPase, as compared with 29.2% (7/24) among those with spindle-shaped cells weakly positive or negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells darkly stained with dThdPase was the factor most strongly related to the response to chemotherapy (odds ratio = 35.513, p = 0.0027). Conclusions: The expression of dThdPase in stromal spindle-shaped cells may be a useful index in predicting the response to 5′-DFUR in patients with gastric cancer.
MUC1 Expression in Intramucosal Colorectal Neoplasms
Authors: Tanimoto Tatsuro , Tanaka Shinji , Haruma Ken , Yoshihara Masaharu , Sumii Koji , Kajiyama Goro , Shimamoto Fumio , Kohno Nobuoki
Published: April 2003

Purpose: The mucin core peptide MUC1 often is detectable in colorectal carcinoma (CRC) tissue and cell lines. However, whether MUC1 in CRC correlates with tumor histogenesis and progression is unclear. We studied the relationship between MUC1 expression in intramucosal CRC and clinicopathologic features, expression of Ki-67, and p53 protein, and apoptosis. Methods: The intramucosal CRC we studied included 140 endoscopically or surgically resected lesions, including 106 low-grade carcinomas and 34 high-grade carcinomas. De novo carcinoma, defined as carcinoma with no adenomatous component, represented 9 of 140 tumors. Three macroscopic types were identified: 57 lesions were polypoid, 55 were superficial and flat, and 28 were granular-type laterally spreading tumors (G-LST). MUC1, Ki-67, and p53 expression were examined immunohistochemically. Apoptotic cells were identified by in situ DNA nick end labeling. Results: MUC1 expression in high-grade carcinomas was significantly more frequent (p < 0.01) than in low-grade carcinomas; expression in adenomas was almost nil. MUC1 expression in polypoid carcinomas was significantly more frequent (p < 0.05) than in superficial carcinomas or G-LST. MUC1 expression in carcinomas with p53 expression was significantly more frequent (p < 0.01) than in carcinomas not expressing p53. No significant correlation was found between expression of MUC1 and Ki-67 labeling index. MUC1 was expressed more frequently in carcinomas with relatively high apoptotic index (p < 0.01). MUC1 expression did not differ between de novo carcinomas and those developing from adenomas. Conclusions: The results suggest that MUC1 is likely to be expressed in the course of colorectal carcinoma development when p53 protein is overexpressed and apoptosis is prominent.
Proliferative Activity of Hürthle Cell Thyroid Tumours
Authors: Cör Andrej
Published: April 2003

To improve our understanding of the basic biological mechanisms of Hürthle cell tumours (HCT), proliferative activity in 20 HCT was determined by Ag-NOR (nucleolar organiser regions) counting and by immunohistochemical markers proliferating cell nuclear antigen (PCNA) and MIB-1. Ten surgically removed Hürthle cell adenomas (HCA) and 10 Hürthle cell carcinomas (HCC) were used for the study. For comparison, a group of 10 thyroid adenomas without Hürthle cells (SA) was also evaluated. There were significant differences in the percentages of PCNA- and MIB-1-positive nuclear areas between HCA and HCC as well as between SA and HCA. The mean number of Ag-NORs per nucleus showed no significant differences between our groups. However, determination of percentages with 5 or more Ag-NORs per nucleus within one focal plane of sections was more useful for the differentiation between thyroid tumours included in our study. The combination of three types of cell kinetic markers may provide insight into the still poorly understood relationships among karyological abnormalities, enhanced proliferation speed, clonal expansion and invasiveness of HCT.