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まれな疾患である孤立性上腸間膜動脈解離に対してステント治療が奏効した症例を経験したので報告する．51歳の男性が，突然の腹痛で来院した．CT上，上腸間膜動脈（superior mesenteric artery；以下，SMAと略記）の造影不良を認め，偽腔閉塞型のSMA解離が疑われ，緊急入院となった．血管造影でSMAの起始部から全長約65mmの解離病変を認めた．バルーン拡張を行い，再狭窄および解離の進行を予防する目的でステント留置術を施行した．SMA還流域全体の血流改善を認め，腹部症状も改善した．MDCTで腸管虚血像を認めず，抗凝固剤および抗血小板剤の使用で経過観察し，順調に回復した．孤立性SMA解離は，腸管壊死，動脈瘤（切迫）破裂を伴う場合は外科的治療の絶対適応となる．薬物療法を中心とした保存療法で軽快する例が多いが，ステント治療は，症例によっては有力な治療の選択肢になりえると考えられた．

はじめに: 腎細胞癌は，肺・骨などに転移を来しやすく，膵臓への転移は比較的少ない．このため，腎癌膵転移の治療方針，手術成績と予後については，現状まだまだ症例蓄積を要する段階である．方法: 当施設にて過去23年で13例の腎癌膵転移を経験し，うち8例に膵切除術を施行した．非切除症例も含め，その術式や予後，合併症などを検討した．結果: 膵切除8症例の術式は，膵体尾部切除4例，膵全摘2例，幽門輪温存膵頭十二指腸切除1例，膵中央切除1例であった．手術死亡はなく，術後合併症を2例に認めた．8症例中5例が生存中で，2例は無再発生存，median survival time（以下，MSTと略記）は152か月であった．膵転移切除術後の残膵再発を1例に認めた．非切除症例は5例あり，非切除理由としては，肺転移，骨転移，肝転移，下大静脈腫瘍栓などであった．非切除症例5例中，現在4例が死亡，予後は最短22か月から最長90か月，MSTは38か月であった．13例中6例が同時性膵転移であったが，同時性膵転移の中にも長期予後を認めている症例が含まれていた．結語: 腎細胞癌膵転移は，膵以外にコントロールできない転移巣がなければ，多発性・孤立性にかかわらず切除適応であると思われるが，その術式に関しては慎重に決定する必要がある．

This report concerns a 68-year-old man with an esophageal gastrointestinal stromal tumor (GIST) surgically resected after preoperative treatment. Endoscopic examination and the biopsy revealed the submucosal tumor in the lower esophagus to be c-kit gene positive, and we diagnosed the tumor as a GIST. Computed tomography showed a 124 × 74 × 115 mm mass with an unclear margin adjacent to the posterior wall of the left atrium and the inferior right pulmonary vein. As we judged the tumor to be locally advanced and unresectable because of its size and invasiveness, we started neoadjuvant therapy with imatinib mesylate to attain downstaging for complete surgical resection. After 3 months of the treatment, the size of the tumor was reduced to 84 × 52 × 85 mm, and it was free from the adjacent organs. Complete surgical resection was performed together with lower esophagectomy. The patient is alive without cancer 2 years after surgery.

Description Background: As the thoracic esophageal carcinoma has a high metastatic rate of upper mediastinal lymph nodes, especially along the recurrent laryngeal nerve (RLN), it is crucial to perform complete lymph nodes dissection along the RLN without complications. Although Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as the useful tool of visual nerve identification, the utilization of IONM during esophageal surgery has not become common. Here, we describe our procedures focusing on a lymphadenectomy along the RLN utilizing the IONM. Methods and Procedures: We first dissect ventral and dorsal side of the esophagus preserving the membranous structure (mesoesophagus), which contains tracheoesophageal artery, RLN and lymph nodes. We next identify the location of the RLN which runs in the mesoesophagus using IONM before visual contact. After that, we perform lymphadenectomy around the RLN preserving the nerve. To evaluate the efficacy of this method, we compared short term surgical outcome of our 36 consecutive cases (neural monitoring group; Nm) of esophagectomy in prone positioning with 56 of our historical cases (conventional method group; Cm). Results: In all 36 cases of Nm group, we could obtain the location information of the RLN before the visual contact. Although the operation time of thoracic part was significantly longer in Nm group compared to Cm group (281 min vs. 254 min each, P = 0.005), postoperative RLN paralysis according to postoperative laryngoscopy was seen in 3 cases (8.3%) after surgical operation in Nm group, which was significantly lower than that in the Cm group (18/56, 32.1%, P = 0.005). As a result, median postoperative hospital stay was significantly shorter in Nm group than Cm group (22 days vs. 39 days each, P = 0.0003). Conclusion: Mesentery-oriented lymph nodes dissection using IONM has substantial advantages to perform accurate and safe thoracoscopic esophagectomy. It could decrease the RLN paralysis and postoperative hospital stay after esophagectomy. Disclosure All authors have declared no conflicts of interest.

Description Introduction Spontaneous esophageal rupture, also known as Boerhaave's syndrome, is an uncommon and potentially life-threatening condition that requires urgent surgical management. We report a case of spontaneous esophageal rupture that was successfully treated by primary closure and drainage laparoscopically. Case report The patient was a 49 year-old man with a history of liver cirrhosis. He experienced sudden-onset epigastric pain triggered by vomiting after drinking alcohol, and transported to our hospital. On admission, a thoracic CT scanning revealed mediastinal emphysema without pleural effusion. We diagnosed BS and performed an emergency operation. We chose laparoscopic trans-hiatal approach as it was thought to be minimally invasive compared with open thoracic surgery. Five trocars were placed in a similar way of gastric cancer surgery. We identified laceration on the left wall of the lower esophagus under assistance of intra-operative upper endoscopy, and conducted drainage and repair by primary closure with continuous barbed suture. Finally, an omental pedicle flap was applied for over sutured site. The operation time was 214 minutes and the amount of blood loss was 50 cc. In the post-operative course, intra-mediastinal abscess was observed and he required antibiotic therapy. However, the patient was discharged on the 16th post-operative day without a serious complication such as anastomotic leakage. Discussion Primary esophageal repair is the gold standard in Boerhaave's syndrome and the approach is usually left thoracotomy. However, if there is no perforation into the thoracic cavity as in our case, less invasive approach should be considered such as laparoscopic trans-hiatal approach. We could observe the lower esophagus completely under a good field of view in this approach. There are several treatments, and it should always be tailored to the patient's condition. Laparoscopic trans-hiatal approach is considered to be useful for the treatment of lower esophageal wall rupture. It is difficult to conduct a comparative study of the various methods that can be used to treat spontaneous esophageal rupture in cases that require emergent surgery, as the number of cases is limited. Therefore, the further accumulation of cases is necessary. Disclosure All authors have declared no conflicts of interest.

まれな症例である副乳頭カルチノイドの1例を経験したので報告する．症例は70歳の男性で，他疾患のフォローにて実施された上部消化管内視鏡検査にて十二指腸副乳頭部付近の不整隆起を指摘され当院へ紹介となった．上部消化管内視鏡検査，ERCP，生検などから副乳頭カルチノイドと診断し，亜全胃温存膵頭十二指腸切除術を実施した．術前検査および術中所見からはリンパ節転移は否定的であったが，病理組織学的検索で#13リンパ節に転移を認めた．副乳頭カルチノイドはまれな疾患であり，過去の報告は本邦内外を含めて17例のみである．通常，カルチノイドのリンパ節転移は深達度および腫瘍径と相関関係にあるとされ，治療選択の際にもこの2点が重要とされるが，副乳頭カルチノイドでは他部位に生じたカルチノイドに比べてリンパ節転移の頻度が非常に高く，通常であれば局所切除が考慮されるような症例に対しても，系統的リンパ節郭清を伴った術式が必要と考えられた．

肺多形癌の腹部転移巣を切除するも，術後3週間でほぼ術前と同じ大きさにまで再発増大を来した症例を経験したので報告する．症例は5か月前に肺多形癌を切除した既往のある50歳の男性で，食欲不振と倦怠感を訴え来院した．腹部CTにて左上腹部に腫瘍を認め，術前診断では消化管間質性腫瘍と判断した．入院後，腫瘍内への出血および自覚症状の増悪を認めたため，準緊急的に開腹腫瘍摘出術を実施した．病理組織学的検査結果は肺多形癌の大網転移であった．肉眼的な腫瘍の遺残は認めなかったが，術後19病日のCTにて術前とほぼ同じ大きさにまで再発増大した腫瘍を認めた．腫瘍はこの後も増大し，腫瘍の横隔膜および肝門部圧迫に伴う呼吸不全と閉塞性黄疸，および腫瘍内出血に伴う貧血より多臓器不全を来し，患者は術後46病日に永眠された．多形癌はまれではあるが，非常に発育が早く予後不良な腫瘍である．この腫瘍の腹腔内臓器転移について報告する．

はじめに：膵癌は予後不良の疾患であり，術後補助化学療法による予後の改善が期待されている．Gemcitabine（以下，GEM）による膵癌術後補助化学療法が，生存期間延長効果に寄与するかどうかを明らかにするため，GEMを用いた膵癌術後補助化学療法の治療成績とその解析を行い，主評価項目を全生存期間として検討した．対象と方法：1981年8月から2007年3月までに浸潤型膵管癌で当外科にて膵切除術を施行した症例213例（切除率55％）を対象とし，うち2002年1月から2007年3月までに，膵切除術後にインフォームドコンセントが得られた80症例をGEMによる化学療法群とし，術後補助療法なしに経過観察された133症例を経過観察群とした．結果：全生存期間でみると化学療法群では経過観察群に比べて有意に良好で（p=0.029；log-rank法），ハザード比は0.785（95％CI：0.642-0.949）であった．層別化因子では，癌遺残度R1例，リンパ節転移陽性例，門脈浸潤陽性例，神経叢浸潤陽性例，膵頭部癌例でそれぞれ経過観察群よりも，GEM投与群で有意に全生存期間延長効果が認められた．考察：膵癌術後GEM補助化学療法は生存期間延長効果があることが強く示唆された．画像診断上進行膵癌を疑っても積極的に切除を目指し，術後GEM補助化学療法を施行することは予後改善に寄与すると考えられる．

症例は67歳の男性で, 近医にて黄疸を指摘され当院紹介となった. 腹部造影CT上肝S5領域の帯状腫瘍陰影像と, 胆管腫瘍栓およびそれに伴う肝内胆管拡張を認めた. 経皮経肝胆管造影検査では胆管腫瘍栓は前区域枝から左肝管, 総肝管まで伸展していた. 胆管擦過細胞診では腺癌, 胆管腫瘍栓生検では肉腫の診断であり, 肝内胆管癌または肝肉腫の術前診断にて肝中央2区域切除・胆道再建・リンパ節郭清を施行した. 切除標本の病理組織学的検査所見では, 病変全体に高分化型腺癌と肉腫が混在し肉腫の一部には軟骨・類骨を認め肝癌肉腫と診断された. 術後16か月現在, 無再発生存中である. 肝癌肉腫は非常にまれな疾患であり, 我々が検索しえたかぎりでは17例を認めるのみで, 胆管腫瘍栓を伴った症例は本症例が初めてであった.

AIM: To retrospectively analyze factors affecting the long-term survival of patients with pancreatic cancer who underwent pancreatic resection. METHODS: From January 2000 to December 2011, 195 patients underwent pancreatic resection in our hospital. The prognostic factors after pancreatic resection were analyzed in all 195 patients. After excluding the censored cases within an observational period, the clinicopathological characteristics of 20 patients who survived ≥ 5 (n = 20) and < 5 (n = 76) years were compared. For this comparison, we analyzed the patients who underwent surgery before June 2008 and were observed for more than 5 years. For statistical analyses, the log-rank test was used to compare the cumulative survival rates, and the χ2 and Mann-Whitney tests were used to compare the two groups. The Cox-Hazard model was used for a multivariate analysis, and P values less than 0.05 were considered significant. A multivariate analysis was conducted on the factors that were significant in the univariate analysis. RESULTS: The median survival for all patients was 27.1 months, and the 5-year actuarial survival rate was 34.5%. The median observational period was 595 d. With the univariate analysis, the UICC stage was significantly associated with survival time, and the CA19-9 ≤ 200 U/mL, DUPAN-2 ≤ 180 U/mL, tumor size ≤ 20 mm, R0 resection, absence of lymph node metastasis, absence of extrapancreatic neural invasion, and absence of portal invasion were favorable prognostic factors. The multivariate analysis showed that tumor size ≤ 20 mm (HR = 0.40; 95%CI: 0.17-0.83, P = 0.012) and negative surgical margins (R0 resection) (HR = 0.48; 95%CI: 0.30-0.77, P = 0.003) were independent favorable prognostic factors. Among the 96 patients, 20 patients survived for 5 years or more, and 76 patients died within 5 years after operation. Comparison of the 20 5-year survivors with the 76 non-survivors showed that lower concentrations of DUPAN-2 (79.5 vs 312.5 U/mL, P = 0.032), tumor size ≤ 20 mm (35% vs 8%, P = 0.008), R0 resection (95% vs 61%, P = 0.004), and absence of lymph node metastases (60% vs 18%, P = 0.036) were significantly associated with the 5-year survival. CONCLUSION: Negative surgical margins and a tumor size ≤ 20 mm were independent favorable prognostic factors. Histologically curative resection and early tumor detection are important factors in achieving long-term survival.

The survival curve of patients who undergo surgical resection of pancreatic cancer displays a steep decline within 1 year and a relatively slow decline thereafter. The patients with a short survival time may have identifiable clinicopathologic factors that lead to rapid relapse. We analyzed clinicopathologic factors in 133 patients who underwent margin-negative pancreatoduodenectomy with extended radical lymphadenectomy for invasive ductal carcinoma of the pancreas to detect factors that could be responsible for the short survival. Tumor size, invasion of the anterior pancreatic capsule, retroperitoneal invasion, portal venous invasion, major arterial invasion, and metastasis to the para-aortic lymph nodes were variables associated with survival time in univariate analysis. Metastasis to the para-aortic lymph nodes was the single independent factor with a significant association with mortality in multivariate analysis. Some 84% of the patients who had positive para-aortic lymph nodes died within 1 year, versus 46% of the patients with negative nodes. Although tumors that involve the para-aortic lymph nodes may technically be resectable, the expected postoperative survival time for most patients is less than 1 year. If para-aortic nodal metastasis is detected, alternative treatment strategies should be considered.

血小板減少を呈した巨大脾過誤腫の1例を経験したので報告する. 症例は24歳の男性で, 2005年3月全身倦怠感があり, 血小板減少を指摘され紹介された. 骨髄生検で造血系腫瘍は否定され, 腹部CTで巨大脾腫瘍による血小板減少と診断された. エコーで腫瘍は脾臓のほぼ全体を占め, 内部不均一であり, 腫瘍内に血流シグナルを認めた. 単純CTではまだらな低吸収域, 造影CTでは腫瘍実質と考えられる高吸収域内に低吸収域がモザイク状に多発していた. MRIではT1強調でムラのある低信号, T2強調で高信号の中に高～低信号の結節を多数認めた. 以上より, 脾腫瘍内に血栓が多発しているものと考え脾臓摘出術を施行した. 摘出標本では大部分が腫瘍と器質化した血栓で占められており, 重量2,650g, 大きさ22×17×12cmで, 病理診断は赤脾髄型過誤腫であった. 本腫瘍は脾過誤腫としては, 文献で調べうるかぎり最大の大きさであった.

We report a case of localized primary sclerosing cholangitis (PSC) which was difficult to distinguish from gallbladder carcinoma. A 75-year-old woman with elevated serum bilirubin was hospitalized and underwent endoscopic nasobiliary drainage (ENBD). There was no history of diseases such as gallbladder stone, pancreatitis, or ulcerative colitis. Cholangiography through the ENBD tube showed localized stenosis of the common bile duct; the gallbladder could not be seen. Angiography showed no encasement of the hepatic artery. Ultrasonography showed a tumor in the cystic duct, and the tumor had invaded the gallbladder and common bile duct. We diagnosed gallbladder carcinoma on radioimaging, and performed an S4aS5 subsegmentectomy of the liver and resection of the extrahepatic biliary tree. Pathologically, no malignant cells were detected, and fibrosis around bile ducts and infiltration of inflammatory cells into hepatic tissue were found. It is well known that PSC is sometimes difficult to differentially diagnose from cholangiocarcinoma. Our case is of high interest because ultrasonography showed findings suggestive of gallbladder carcinoma. It is therefore necessary to keep the possibility of PSC in mind for the diagnosis and treatment of such localized biliary stenosis.

A considerable amount of evidence collected from several experimental systems and clinical studies with nonsteroidal Anti-inflammatory drugs (NSAIDs) indicates that Cox-2 may play a major role in colorectal tumorigenesis, but little information about Cox-2 expression in pancreatic tumors is available. In this study, we investigated Cox-2 expression by means of both immunohistochemical analysis and immunoblot analysis in pancreatic tumors.Fifty invasive ductal adenocarcinomas and 26 intraductal papillary-mucinous tumors (IPMTs) were used for immunohistochemical analysis, and five pancreatic cancer tissues and five pancreatic cancer cell lines for immunoblot analysis.Cox-2 was expressed in 72% of the invasive ductal adenocarcinomas, 31% of intraductal papillary-mucinous adenocarcinomas, and none of intraductal papillary-mucinous adenomas. The expression rate of Cox-2 in intraductal papillary-mucinous adenocarcinomas was significantly higher than that in intraductal papillary-mucinous adenomas, and that in invasive ductal adenocarcinomas was significantly higher than that in intraductal papillary-mucinous carcinomas. However, there was no significant correlation between Cox-2 expression and the prognosis and clinicopathological factors. Immunoblot analysis identified Cox-2 in all of pancreatic cancer tissues and 60% of cell lines.The biological role of cyclooxygenase-2 (Cox-2) in carcinoma cells should be investigated with reference to the cancer progression of the pancreas.

Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range,220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than 3(1/2) years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases.

The preoperative determination of thelocalization of a small insulinoma is sometimesdifficult using routine imaging techniques. We have usedthe selective arterial calcium injection (SACI) test todetermine the location of the tumor preoperatively. Thepathophysiologic basis of the SACI test is based on theresponsiveness of insulinomas to calcium injected intothe feeding artery. In this study, we demonstrated the in vitro response of the insulinoma cellsto the extracellular calcium challenge by usingprimary-cultured insulinoma cells. Human insulinomacells were obtained from three patients. MIN6 cells(normal pancreatic B cells) were used as a control;their insulin response to various stimuli resembles thatof normal B cells. The insulin secretory dynamics inresponse to extracellular calcium were observed using a perfusion system. Second, the change ofthe concentration of cytosolic free calcium([Ca2+]i) was monitored byfluorometry using fura-2/AM. When the concentration ofextracellular calcium ([Ca2+]o) was changed from 2.54 mM to 10 mM, insulinsecretion from the insulinoma cells was markedlyincreased within 6 min (10- to 18-fold at maximum), andrapidly returned to the basal level; at the same time, [Ca2+]i was immediatelyelevated and reached a peak within 1 min. In contrast,in the MIN6 cells, the insulin secretion and [Ca2+]iwere not significantly changed when[Ca2+]o was switched to 10 mM. The results of these in vitro experiments agreedwith the clinical results of the SACI test. The positiveresponse of the insulinoma to the SACI test is probablydue to the different response of insulinoma cells to the extracellular calcium challengecompared with normal B cells. The role of[Ca2+]i may be important in themechanism underlying the SACI test.

Endocrine tumor of the pancreas is potentially malignant. A multicenter analysis of these tumors was conducted to clarity the present status of their surgical management and the subsequent long-term surgical results. The Japan pancreatoduodenectomy (JPD) study group carried out the study; 368 patients were enrolled and variables related to tumor characteristics, surgery, and survival were retrospectively analyzed. There were 222 patients with functioning tumor and 143 patients with nonfunctioning tumor. Malignant tumor was found in 140 of 368 (38%) of the patients, and 63/140 (45%) of these patients had metastatic lesion; the most common site of the metastasis was liver 34/136 (25%), followed by regional lymph nodes 26/136 (19%). Pancreatic resection was performed in 91% of patients with nonfunctional tumor and in 83% of those with malignant tumor, and 73% of the pancreatic resections were done with lymph node dissection. The overall 5-year actuarial survival rate was 76% in patients with malignant tumor. The actuarial 5-year survival rate was 93% in the patients without metastasis and 83% in patients who received curative resection. Multivariate analysis showed that the presence or absence of synchronous metastasis was the sole significant prognostic factor. The results suggest that: (i) malignant endocrine tumor of the pancreas is a curable malignancy when pancreatic resection with lymph node dissection is adopted and (ii) that synchronous metastasis is the dominant prognostic factor.

Metastasis to the breast from extramammary malignancies is rare. This is the third case report of metastatic breast cancer from esophageal cancer. We report the clinical, radiographic, and pathologic findings of a 57-year-old woman who underwent esophagectomy for esophageal cancer and developed metastatic cancer 2 years later. Pathologic examination of a resected specimen of the breast revealed squamous cell carcinoma invading the mammary glands. Estrogen receptor and axillary lymph node metastasis were negative with immunostaining. She is alive 6 months after the modified radical mastectomy.

Both Zollinger-Ellison syndrome (ZES) and Helicobacter pylori infection are major etiologic factors for peptic ulcer. The aim of this study was to investigate the effect of H. pylori infection on ZES with special reference to acid secretion. Sixteen patients with ZES were selected (median age, 59 years; range, 39–66 years; M/F, 9/7), and H. pylori status, ulcer location, gastric acid secretion, serum pepsinogen (PG) I and II concentrations, and PG I/II ratio were determined. The seroprevalence of H. pylori infection was 50%, whereas active H. pylori infection was seen in only 25% of the patients. Thirteen patients had duodenal ulcer (DU), 1 had gastric ulcer (GU), and 2 had both GU and DU. DU was seen in both H. pylori-positive and H. pylori-negative patients, whereas GU was found only in H. pylori-positive patients. Both basal and maximal acid outputs were significantly lower in H. pylori-positive patients than in H. pylori-negative patients (P < 0.05). Moreover, both serum PG I and the PG I/II ratio were significantly lower in H. pylori-positive patients than in H. pylori-negative patients. These results indicate that ZES is an independent risk factor for DU, but H. pylori infection may play some role in the development of GU in ZES. In patients with ZES, H. pylori infection may reduce both hypersecretion from parietal cells and PG I secretion from chief cells, and hyperacidity of the stomach in ZES may have eradicated H. pylori in some patients.

Background. The growth of both cancer cells and fetal tissue is rapid; however, cancer cells de-differentiate and proliferate in a disorderly manner, whereas fetal tissues differentiate and proliferate in an orderly manner. Thus, there may be both common and different factors that are involved in the process of the uncontrolled cell growth of pancreatic cancers and the development of the fetal pancreas. The common part of the mechanisms should be in the regulation of the cell cycle, resulting in rapid proliferation via such mechanisms as growth stimulation and avoidance of apoptosis. Therefore, in the current study we investigated the expression of apoptosis-related proteins in fetal pancreatic tissues. Methods. Sixteen human embryonic and fetal pancreatic tissues obtained between 6 and 32 wk of gestation were used. We immunohistochemically examined the protein expression of Bcl-2, Bcl-XL, Mcl-1, and Bax. Further, the expression of insulin, glucagon, and proliferting cell nuclear antigen (PCNA), and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining were examined. Results. In embryonic and fetal pancreatic tissues, Bcl-2 was not detected in any type of pancreatic cell (acinar, ductal, or islet). Bcl-XL was expressed in all types of pancreatic cells throughout the gestation. Mcl-1 was expressed in all types of pancreatic components, and strongly expressed in the margin of the islets. Bax, a pro-apoptotic protein, was expressed in all components. PCNA was strongly expressed in the embryonic and fetal pancreas, especially in early stages of gestation; however, TUNEL staining was negative in all samples. At least one antiapoptotic protein was expressed in all types of pancreatic cells. Conclusion. The results of the current study indicate that active proliferation and avoidance of apoptosis take place in embryonic and fetal pancreatic tissues, which may be controlled by particular combinations of apoptosis-related proteins. Among these proteins, Bcl-XL and Mcl-1 may play an important role in the proliferation and differentiation of the embryonic and fetal pancreas.

It has generally been recognized that for adenocarcinoma of the pancreas, surgical resection provides the only chance for cure. In this study, we have analyzed the long-term survival of 141 patients with invasive ductal adenocarcinoma of the pancreas who received macroscopically curative resection. Multivariate analysis demonstrated that comprehensive stage of the tumor, curability of the resection, and adjuvant radiation therapy were independent prognostic factors. Pancreatectomy in this study was done with an extensive retroperitoneal clearance of para-aortic lymph node and nerve tissues, so-called extended resection. Survival curves of these patients revealed that the R0 resection is essentially necessary for long-term survival. Survival curve without microscopic lymph node metastasis was significantly better than that with node metastasis; however, 3 patients with node metastasis have been alive for more than 3 years. The survival curve of the patients who received adjuvant radiation therapy was better than of those who underwent surgery alone, and postoperative regional chemotherapy with continuous 5-FU infusion decreased hepatic metastases within 6 months. The results suggest that local recurrence of pancreatic cancer might possibly be controlled by extended resection and adjuvant irradiation, and early development of hepatic metastases might be controlled with regional chemotherapy.

We investigated the role of neutrophils and the involvement of apoptosis in cerulein-induced acute pancreatitis. Male Sprague-Dawley rats were divided into 2 groups. In the control group, acute pancreatitis was induced by subcutaneous injections of cerulein. In methotrexate-treated group, the rats received intraperitoneal injections of methotrexate to produce neutrophil depletion before the injections of cerulein. The rats were sacrificed at the indicated time points until 72 h after the first injection of cerulein. Neutrophil depletion ameliorated pancreatic edema and vacuole formation in acinar cells during the early stages of cerulein-induced acute pancreatitis. Electron microscopy, DNA gel electrophoresis and in situ nick end-labeling revealed the involvement of apoptosis in acinar cells in cerulein-induced acute pancreatitis. Furthermore, the number of apoptotic acinar cells in neutrophil-depleted rats showed an about 2-fold increase during the late stages when compared with those in the control rats. Our results suggest that neutrophil depletion in cerulein-induced pancreatitis leads to amelioration of pancreatic injury during the early stage, and enhancement of apoptosis by neutrophil depletion occurs during the late stage.

Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700 +/- 4300 IU/day), and recovered on days 9-15 (48,000 +/- 8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440 +/- 260 IU/day) and BT-PABA test results were low (45 +/- 17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient, rs = 0.715, P0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.

Clinical trial of intraoperative radiation and external-beam radiation combined with twice-weekly gemcitabine for the treatment of locally advanced pancreatic cancer

(BACKGROUND) Agonistic anti-Fas antibody (CH-11) has been reported to have little growth inhibiting potency to almost all pancreatic cancer cell lines (PCCs). DcR3 is antagonistic soluble receptor against Fas ligand, which belongs to a new TNF superfamily. Genomic amplification and mRNA expression of DcR3 have been reported in colon and lung cancers. However no information is available of the DcR3 status in PCCs. Here in the study we examined the effect of CH-11 in the presence of IFN,yand DcR3 genomic amplification and mRNA expression in PCCs. (METHORD) 1) PCCs (AsPC-1, BxPC-3, Capan-2, CFPAC-1, HPAC, MIA PaCa-2) were incubated with various concentrations of CH-11 after pretreatment with IFN~. Attached ceils were harvested and counted using Coulter Counter. 2) Genomic DNA was extracted from PCCs and quantitative PCR was performed using TaqMan system. The ratio of DNA copy number of DcR3 to beta actin was calculated. 3) mRNA was isolated from subconfluent PCCs and converted to cDNA. Quantitications of mRNA of DcR3 and beta actin were carried out with TaqMan RT-PCR. (RESULT) 1) CH-11 suppressed the growth of PCCs except for AsPC-1 to various extents when pretreated with IFN-/. 2) BxPC-3 and HPAC showed DcR3 genomic amplification (2.6 + 0.4, 2.9 + 0.4 times). Genomic amplification of DcR3 and the sensitivity to CH-11 were not correlated in PCCs. 3) Capan-2 and CFPAC-1 strongly expressed DcR3 mRNA. DcR3 mRNA expression and the sensitivity of CH-11 were not correlated in PCCs. Furthermore genomic amplification and mRNA expression of DcR3 were not correlated each other in PCCs. (CONCLUSION) Agonistic anti-Fas antibody inhibited the growth of pancreatic cancer cell lines in the presence of IFN~. Several pancreatic cancer cell lines strongly expressed DcR3 mRNA, while DcR3 genomic amplification and mRNA expression are not related to the sensitivity to CH-11 in pancreatic cancer cells. The expression of DcR3 is not involved in the inhibitory effect of CH-11 on pancreatic cancer cell growth.