Japanese Journal of Clinical Oncology

Jung-Hyun Yang, Seok Jin Nam, Tae Seung Lee, Hae Kyung Lee, Sung Hoo Jung, Byung Tae Kim

doi: 10.1093/jjco/hye007pmid: 11256834

Background: Although axillary lymph node status is an important prognostic factor and axillary dissection is regarded as the gold standard for staging, it requires radical surgery which is accompanied by considerable postoperative problems such as lymphedema. This study was carried out to evaluate the diagnostic accuracy of preoperative positron emission tomography (PET) and intraoperative frozen biopsy of sentinel lymphadenectomy (SLND) in detecting axillary lymph node metastasis. Methods: We studied 18 patients who had preoperative PET and SLND for breast cancer in the Department of Surgery at Samsung Medical Center. They all had preoperative PET with a radiolabeled glucose analogue (( 18 F)FDG) to visualize primary tumors and metastatic nodes. Isosulphan blue dye was used for intraoperative SLND. Frozen and permanent biopsies were then compared after full axillary dissection. Results: In 18 cases, six had positive metastatic nodes in the permanent biopsy of full axillary dissection but were negative in three cases by preoperative PET. There was one false negative result by frozen biopsy of SLND which was later shown to be positive by permanent biopsy. The sensitivity and specificity of SLND and PET for detecting axillary node metastasis were 83, 100% and 50, 100%, respectively. Conclusion: Although both methods are good for axillary nodal status, the intraoperative frozen biopsy result of SLND was superior to preoperative PET in our preliminary study. Key words

Shuichi Okada, Hideki Ueno, Takuji Okusaka, Masafumi Ikeda, Junji Furuse, Yasushi Maru

doi: 10.1093/jjco/hye003pmid: 11256843

Background: Gemcitabine is the most promising new agent currently being tested in pancreatic cancer. The present study was conducted to confirm the tolerability of a weekly schedule of gemcitabine at a dose of 1000 mg/m 2 in Japanese patients with advanced pancreatic cancer. Methods: The primary end-point was to evaluate the frequency of dose-limiting toxicity. Gemcitabine 1000 mg/m 2 was administered over 30 min weekly in two schedules: gemcitabine ×3 every 4 weeks (Schedule 1) and gemcitabine ×7 followed by a week of rest and then gemcitabine ×3 every 4 weeks thereafter (Schedule 2). At least three patients entered each schedule and three additional patients were treated in the presence of dose-limiting toxicity. Results: Eleven chemo-naive patients with a good Karnofsky performance status of ≥80 points and distant metastasis were entered into this trial. In Schedule 1, no dose-limiting toxicity was observed in the three patients. In Schedule 2, the evaluation of dose-limiting toxicity was complete in six of the eight enrolled patients and two patients showed dose-limiting toxicity in this Schedule; one patient experienced both grade 4 leukocytopenia and grade 4 neutropenia, and both grade 4 neutropenia and grade 3 GOT/GPT increased in another patient. Two patients (18%) showed a partial response and a clinical benefit response was also achieved in two (29%) of the seven evaluable patients. Conclusion: Gemcitabine 1000 mg/m 2 weekly ×7 followed by a week of rest and weekly ×3 every 4 weeks thereafter may be tolerated in Japanese patients with advanced pancreatic cancer. Key words

Tatsuo Igarashi, Toyofusa Tobe, Hiroaki Kuramochi, Koichiro Akakura, Tomohiko Ichikawa, Satoshi Hamano, Noriyuki Suzuki, Yuzo Furuya, Haruo Ito

doi: 10.1093/jjco/hye004pmid: 11256835

Background: Estimation of survival probability of individual patients with metastatic renal cell carcinoma was difficult owing to diverse prognostic factors. We analyzed serum immunosuppressive acidic protein (IAP) levels and the cutoff value, then tested its validity for assessing patients’ prognoses. Methods: Serum IAP was measured longitudinally in 84 patients with metastatic disease. Before therapy, cutoff levels of IAP were tested every 20 µg/ml between 600 and 1200 µg/ml. The prognostic importance of IAP and its cutoff level was estimated. Results: The cutoff level of IAP was set at 800 µg/ml for 40 patients who had metastatic disease with the primary tumor in situ and for 44 patients with recurrent disease. IAP was found to be a significant prognostic factor for both patient groups. Conclusions: Serum IAP is an important prognostic factor for patients with metastatic renal cell carcinoma. Stratification of patients according to prognosis is feasible using the cutoff level. Key words

Manabu Kuriyama, Yoshito Takahashi, Masafumi Sahashi, Yoshinari Ono, Takuji Tanaka, Hiroyuki Shimizu, Shinichi Ohshima

doi: 10.1093/jjco/hye008pmid: 11256836

Objective: This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer. Methods: A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores. Results: A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values <40 ng/ml showed a good indication for this endocrine chemotherapy. Conclusion: This endocrine chemotherapy was confirmed to be tolerable and significantly effective in the delay of disease progression, which leads to longer survival in patients with prostate cancer. Key words

Nam Kyu Kim, Jin Sik Min, Jea Kun Park, Seong Hyun Yun, Jin Sil Sung, Hyun Chul Jung, Jae Kyung Roh

doi: 10.1093/jjco/hye009pmid: 11256837

Background: Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. Methods: Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m 2 ) and leucovorin (20 mg/m 2 ) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) ( n = 14). Oral doxifluridine (700 mg/m 2 /day) and leucovorin (20 mg/m 2 ) were given daily during radiation treatment ( n = 14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging ) and NR (no response). Results: Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm ( p = 0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence during the follow-up periods were 1/14 (7.1%) in the IV arm and 2/14 (14.3%) in the Oral arm, respectively ( p = 0.307). One local recurrence was observed in the Oral arm. Conclusion: Even though the results were not entirely reliable owing to the small number of patients enrolled, oral doxifluridine-based chemotherapy as preoperative chemoradiation for advanced rectal cancer did not show any significant advantages over intravenous infusion. Key words

Hiroshi Matsubara, Atsushi Makimoto, Jun Takayama, Takeshi Higa, Takeshi Saito, Yoshinobu Kanda, Ryuji Tanosaki, Shin Mineishi, Mutsuro Ohira, Yoichi Takaue

doi: 10.1093/jjco/hye001pmid: 11256838

Background: The benefits of allogeneic peripheral blood stem/progenitor cell transplantation (PBSCT) over bone marrow transplantation (BMT), if any, have not been seriously evaluated in a pediatric population. We report here our experience with this procedure and demonstrate rapid engraftment to reduce procedure-related complications and enhanced allogeneic immune reaction to reduce leukemic relapse. Methods: The feasibility of PBSCT was reviewed retrospectively. Four patients (2 AML and 2 ALL, aged 8–18 years) underwent allogeneic PBSCT for relapsed leukemia after primary allogeneic BMT ( n = 2), for active hepatosplenic fungal abscess ( n = 1) or for refractory relapse with conventional chemotherapy ( n = 1). Four healthy donors (aged 10–49 years) received granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day by subcutaneous injection for 5 days. An individualized cytoreductive regimen was used before transplantation. Results: No significant toxicities were observed in normal donors on G-CSF treatment or at collection of PBSC. After PBSCT, no significant acute toxicities were observed and the median duration to an absolute granulocyte count of 0.5 × 10 9 /l and a platelet count of 20 × 10 9 /l was 16 and 21 days, respectively. Although none of our patients developed acute graft-versus-host disease (GVHD), two developed chronic GVHD involving the liver and skin. Among those who developed chronic GVHD, one died of recurrent disease and another died of pneumonia 235 days after PBSCT. The two remaining patients have been alive without evidence of disease with follow-ups of 193 and 123 days, respectively. Conclusions: Allogeneic PBSCT can be a safe procedure in a pediatric population with fewer acute complications, although the potential risk of G-CSF treatment in normal donors should be seriously weighed against the existing risks of marrow aspiration under general anesthesia. The risk of chronic GVHD may need to be balanced against a possible graft-versus-leukemia benefit in patients at higher risk of leukemic relapse. Key words

Hidenori Kawasaki, Kanji Nagai, Tomoyuki Yokose, Junji Yoshida, Hironobu Ohmatsu, Yutaka Nishiwaki

doi: 10.1093/jjco/hye005pmid: 11256839

We report a case of a 46-year-old man with a 7 mm lung adenocarcinoma with mediastinal nodal involvement and lymphangiosis carcinomatosa. The resected right middle lobe contained a 7 mm well-differentiated papillary adenocarcinoma and lymphatic vessels towards the hilum were severely involved. The disease was pathologically diagnosed as T1N2M0. Six months after the operation, malignant pleural effusion and multiple bone metastases developed and he died 21 months after the operation. This case indicates that even a very small-sized lung cancer, 1 cm or smaller, could be biologically highly malignant. Key words

Katsumi Takano, Yoshihito Ichikawa, Hajime Tsunoda, Masato Nishida

doi: 10.1093/jjco/hye002pmid: 11256840

Uterine inversion caused by uterine sarcoma is a rare condition with 12 reported cases to date according to a MEDLINE search. We report two cases of this rare condition. A 71- and a 72-year-old woman presented with uterine sarcomas rapidly extruded into the vagina. In both cases, magnetic resonance imaging (MRI) scans showed U-shaped uterine cavities and the pedicles of these tumors were attached to the uterine fundi. Pathological examination confirmed a leiomyosarcoma and a heterologous carcinosarcoma. Uterine inversion can occur when uterine sarcoma rapidly increases in size and extrudes into the vagina. MRI should be performed in the diagnosis of this rare combination. Key words

Shin Mineishi, Takeshi Saito, Yoshinobu Kanda, Ryuji Tanosaki, Kensei Tobinai, Yoichi Takaue

doi: 10.1093/jjco/hye006pmid: 11256841

G-CSF administration may not affect the rate of engraftment unless sufficient numbers of stem cells are transplanted. However, there might be some cases in which neutrophil recovery is delayed after stem cell transplantation despite a relatively fast recovery of platelet counts and total white blood cell counts. This delayed engraftment might be observed in either autologous or allogeneic stem cell transplantation. Here we report four cases with delayed neutrophil engraftment which subsequently improved with administration of a minimal dose of G-CSF. As the response occurred on the day following G-CSF administration, a mobilization defect is suspected to be the mechanism of this delayed engraftment. Key words

doi: 10.1093/jjco/31.1.46pmid: N/A

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