Kouichi Hirata

The effect of adjuvant and neoadjuvant chemo(radio)therapy on survival in 1,679 resected pancreatic carcinoma cases in Japan: report of the national survey in the 34th annual meeting of Japanese Society of Pancreatic Surgery

BACKGROUND Pancreatic carcinoma causes more than 20,000 deaths every year in Japan. The role of (neo-) adjuvant chemotherapy for pancreatic carcinoma is still controversial. METHODS At the 34th Annual Meeting of the Japanese Society of Pancreatic Surgery in 2007, questionnaires were distributed regarding the use of (neo-) adjuvant chemo(radio)therapy for pancreatic carcinoma between 2001 and 2005. RESULTS Sixty of the 146 member institutions responded to the questionnaires. There were a total of 1,846 cases of resected pancreatic carcinoma between 2001 and 2005. The study population had a greater proportion of males, and a mean age of 65.3 years (range 34-90 years). The lesion was located in the head of the pancreas in 1,204 cases (71.7%), in the body in 353 cases (21.0%), and in the tail in 111 cases (6.6%). Overall survival rates were 67.3% at 1 year, 36.0% at 2 years, and 23.9% at 3 years, respectively. Adjuvant chemotherapy (usually involving gemcitabine) was used in 66.0% of cases. The use of adjuvant chemotherapy was found to improve the overall survival rate. Interestingly, adjuvant chemotherapy only improved survival in late-stage (UICC stages IIB, III, and IV) but not early stage (IA, IB, and IIA) patients. Survival was treatment duration-dependent, with patients who received more than 12 months of therapy having a 3-year survival rate of 51.2%. CONCLUSION This high volume retrospective data indicated the promising effect of gemcitabine-based adjuvant chemotherapy and the rational duration of adjuvant chemotherapy should be determined in the future prospective studies.

Biological heterogeneity of the peptide-binding motif of the 70-kDa heat shock protein by surface plasmon resonance analysis

70-kDa heat shock protein family is a molecular chaperone that binds to a variety of client proteins and peptides in the cytoplasm. Several studies have revealed binding motifs between 70-kDa heat shock protein family and cytoplasmic proteins by conventional techniques such as phage display library screening. However, little is known about the binding motif based on kinetic parameters determined by surface plasmon resonance analysis. We investigated the major inducible cytosolic 70-kDa heat shock protein (Hsp70)-binding motif with the human leukocyte antigen B*2702-derived peptide Bw4 (RENLRIALRY) by using a Biacore system based on surface plasmon resonance analysis. The KD value of Hsp70-Bw4 interaction was 1.8 × 10-6 m. Analyses with truncated Bw4 variant peptides showed the binding motif of Hsp70 to be seven residues, LRIALRY. To further study the characteristics of this motif, 126 peptides derived from Bw4, each with single amino acid substitution, were synthesized and analyzed for Hsp70 binding affinity. Interestingly, the Hsp70 binding affinity was abrogated when the residues were substituted for by acidic (Asp and Glu) ones at any position. In contrast, if the substitute residue was aromatic (Trp, Tyr, and Phe) or an Arg residue at any position, Hsp70 binding affinity was maintained. Thus, this study presents a new binding motif between Hsp70 and peptides derived from the natural protein human leukocyte antigen B*2702 and may also elucidate some characteristics of the Hsp70 binding characteristic, enhancing our understanding of Hsp70-binding determinants that may influence diverse cellular and physiological processes.

CHANGES IN THE TREATMENT FOR ACUTE PANCREATITIS AFTER INTRODUCTION OF THE EVIDENCE-BASED PRACTICE GUIDELINES

2003年にエビデンスに基づいた急性膵炎の診療ガイドラインが作成された後，3年を経過し，日本腹部救急医学会急性膵炎診療ガイドライン再評価委員会は，関連団体に所属する医師にアンケートを実施し，ガイドライン前後での診療行為の変化などについての調査を行った．診療ガイドラインによってガイドラインに沿った診療行為の変化が多くの領域で認められた．ガイドライン前後（2002年と2004年）での重症膵炎症例数の増加（363例から524例）と死亡率の低下（10.2％から7.6％）が示唆された．しかしながら，関連領域の専門家であってもガイドラインを読んでいない医師も少なくなく，ガイドラインの普及がまだ十分でないことや，診療行為に変化をもたらしえない場合もあることが判明した．これらの結果や記述式の御提案を改訂版作成に役立てたいと考えている．また，現在，改訂作業が始まっており，フィードバックを頂き改変を行った後，2007年3月に改訂版を刊行する予定である．

A CASE OF SYNCHRONOUS FOUR COLORECTAL CANCER WITH INTUSSUSCEPTION

An 81-year-old man was seen at the hospital because of abdominal distention and severe constipation. An elastic hard tumor was palpable by the digital examination and it was downward with an increase in abdominal muscular pressure. Barium enema showed an intussusception of the sigmoid colon and made it release successfully. Total colonoscopy showed two tumors (Ip, Is) in the rectum, two (type 2, Ip) in the sigmoid colon, one (Ip) in the descending colon, one (Is) in the transverse colon and two (Ip, Is) in the ascending colon. Three of them were diagnosed as adenocarcinoma in their biopsy specimen. We performed low anterior resections for them and local resection for the other tumors under colonoscopy during operation. Pathohistological examination revealed adenocarcinamas in four lesions, with different depth of invasion each other (m, sm. mp, and ss). Other lesions were tubular or tubulo-villous adenoma with cellular atypia ranging from moderate to prominent.It has recently been reported that the hereditary factor seems to be involved in the etiology of multiple colorectal cancer. It is important to interview the patient about their family history and several gene analysis would be required for the patient with risk factors. In the case of multiple colorectal cancers, it is sometimes difficult to decide the extent of colectomy; partial or total colectomy in the number of lesions. Intraoperative colonoscopy is convenient and supportive technique in determining more adequate partial colectomy in the patients with low number of lesions.

A CLINICAL STUDY OF GASTRIC SARCOMAS

過去10年間に当教室で経験した胃肉腫17例について検討した.全胃悪性腫瘍769例の2.2%で, 悪性リンパ腫 (細網肉腫) 5例, 平滑筋肉腫11例, 癌肉腫疑1例である.悪性リンパ腫は胃内・浸潤型が多く, 転移はリンパ行性にあり予後が悪い.しかし, 腫瘍細胞が粘膜筋板までにとどまる, 早期胃癌に準ずると早期細網肉腫と考えられる1例のみが生存中である.これに対し平滑筋肉腫は胃外.限局型が多く, リンパ行性転移例はなかったが, 血行性転移は2例にあった.血行性転移の有無の可能性, あるいは予後の判定にはStoutらが唱えた腫瘍組織中における細胞分裂数による指標が臨床的に重要な意義があると考えられた.