Takashi Hatori

A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer

Background:This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer.Methods:Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m−2 over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles.Results:Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40–0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51–1.14); P=0.19).Conclusion:The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.

Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial.

PurposeAlthough the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up.MethodsPatients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio.ResultsThe surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P < 0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate.ConclusionLocally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

EBM-based Clinical Guidelines for Pancreatic Cancer (2013) Issued by the Japan Pancreas Society: A Synopsis

Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer

PurposeThe GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed.MethodsThe results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011.ResultsThe median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79–1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75–1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS.ConclusionOur survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer.Trial registrationClinicalTrials.gov: NCT00498225.

Health-related quality of life in a randomised phase III study of gemcitabine plus S-1, S-1 alone and gemcitabine alone for locally advanced or metastatic pancreatic cancer: GEST study

Objective: This study was performed to compare health-related quality of life (HRQOL) of gemcitabine plus S-1 (GS), S-1 alone and gemcitabine alone as first-line chemotherapy for locally advanced or metastatic pancreatic cancer in the GEST (Gemcitabine and TS-1 Trial) study and to assess the impacts of adverse events and tumour response on HRQOL. Methods: Patients were randomly assigned to receive gemcitabine alone (1000 mg/m2 weekly for 3 of 4 weeks), S-1 alone (80, 100 or 120 mg/day twice daily for 4 of 6 weeks) or GS (gemcitabine at 1000 mg/m2 weekly plus S-1 at 60, 80 or 100 mg/day twice daily for 2 of 3 weeks). HRQOL was assessed using the EuroQoL-5D (EQ-5D) questionnaire at baseline and weeks 6, 12, 24, 48 and 72. EQ-5D scores, quality-adjusted life months (QALMs), quality-adjusted progression-free months (QAPFMs) and time until definitive HRQOL deterioration (TUDD) were compared among the three groups. The impacts of adverse events and tumour response on EQ-5D scores were analysed. Results: Including EQ-5D scores after death as 0, the mean profile was significantly better in the GS than gemcitabine group (difference, 0.069; p=0.003), but not the S-1 group (difference, −0.011; p=0.613). The mean profiles until death were similar in the three groups. QALMs, QAPFMs and TUDD were significantly longer in the GS than gemcitabine group (p<0.001, p<0.001 and p=0.004, respectively), but not the S-1 group (p=0.563, p=0.741 and p=0.701, respectively). Fatigue, anorexia and tumour response were significantly associated with changes in EQ-5D scores. Conclusions: GS achieved better HRQOL than gemcitabine alone, resulting a good balance between overall survival and HRQOL benefits. S-1 alone provides HRQOL similar to that provided by gemcitabine alone. Preventing fatigue and anorexia and maintaining better response would improve HRQOL.

Right lateral decubitus approach to a laparoscopic modified Hassab's operation

The lateral approach is the standard for laparoscopic splenectomy. However, when the modified Hassabs operation is performed laparoscopically, the patient is placed in the supine position and then the right semi‐lateral or lateral decubitus position. Based on our experience with laparoscopic adrenalectomy and splenectomy, we laparoscopically performed the modified Hassabs operation with the patient in the right lateral decubitus position.

Evaluation of the Extended Radical Operation and Intraoperative Radiation Therapy for the Cancer of the Head of the Pancreas. Aspects of Mode of Extension and Recurrence.

通常型膵頭部癌切除282例を対象に, 進展・再発形式から拡大手術の評価と術中放射線療法の有効性を検討した.膵外への直接進展は93%に見られ, stage III, IVの進行癌が86%を占めた.拡大手術の治癒切除率は49%と有意に向上し, 術後合併症発生率, 手術死亡率はおのおの19%, 4%と安全に行われた.拡大手術の1生率, 3生率, 5生率は各々44%, 13%, 9%で, 5年生存例10例を得た.治癒切除例の再発形式は, 後腹膜再発, 肝転移が63%, 46%と高率であった.1988年以降, 術前進展度診断による適応選択を行い, 臨床病期IV期を拡大手術の適応外とした結果, 1987年以前に比べて生存率は有意差はないがやや良好である傾向が認められた.切除例に対する術中放射線療法は, 初期のプロトコールでは生存率・再発形式の面からは有効性は認められず, 現在は, 拡大手術と同様の適応選択を行ってprospective randomized studyにより術中放射線療法の有効性を検討している.

Indications of an Extended Radical Operation for the Carcinoma of the Head of the Pancreas.

膵頭部癌の術前進展度診断能, 治癒切除可能性から拡大手術の合理的な適応選択について検討した.対象はcomputed tomography, 血管造影が共に施行された通常型膵管癌75例である.膵癌取扱い規約による各進展因子の術前進展度正診率は, Aが92.0%と高く, PV, Rp, Plx, Sでは49.4%, 62.7%, 58.7%, 61.3%で, 浸潤のない例や高度進展例に比べ軽度進展例の診断は必ずしも容易ではなかった.治癒切除可能性は, A0で65.1%, PV0～2で46.4～86.4%, Rp0～2で50.0～100.0%, PlX0～2で45.8～91.7%であったが, A1～3, PV3, Rp3, PlX3では0～16.7%にすぎなかった. 局所高度進展例の術前診断は困難ではないが治癒切除の可能性は極めて低く, 拡大手術の適応外とすべきである. 軽度進展例の診断は必ずしも容易ではないが, 拡大手術で可及的に治癒切除を追求すべきである. 膵頭部癌のさらなる治療成績の向上のためには術前進展度診断に応じた合理的な適応選択が必要と考える.