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Objective To identify the risk factors for incisional surgical site infection (SSI) in patients undergoing emergency surgery for colorectal perforation. Summary of Background Data Emergency surgery for colorectal perforation carries an especially high risk of incisional SSI. Although the risk factors of incisional SSI after colorectal surgery have been analyzed, no study has focused exclusively on patients with colorectal perforation. Methods Patients with colorectal perforation who underwent emergent surgery from 2010 to 2015 were enrolled. The factors associated with the occurrence of postoperative incisional SSI were evaluated. Results We enrolled 108 patients with colorectal perforation who underwent an emergency operation. Of these, 13 patients who died within 30 days after surgery were excluded. The mean age of the 95 study patients was 70 ± 13 years; 48 (51%) patients were male. The incisional SSI group comprised 26 patients (27%). Multivariate logistic regression analysis showed that stoma creation [odds ratio: 11.34; 95% confidence interval: 2.06–214.14] was an independent risk factor for incisional SSI. However, none of the clinical indicators of severe peritonitis and sepsis, including body temperature, systolic blood pressure, heart rate, preoperative white blood cell count, and C-reactive protein, were associated with the occurrence of incisional SSI. Conclusions Stoma creation was an independent risk factor for postoperative incisional SSI. Therefore, in this patient population, meticulous postoperative wound management is essential.

Acute appendicitis is the most common general surgical problem encountered during pregnancy. Laparoscopic appendectomy (LA) is widely accepted as a minimally invasive procedure for acute appendicitis. However, LA during the third trimester is associated with problems, including technical difficulty, risk of preterm delivery, and fetal loss. We successfully managed three cases of LA during the third trimester between 2011 and 2016. None of the cases required conversion to an open procedure, and none of the patients had postoperative complications and/or fetal loss. We reviewed the literature using the PubMED database from 2007 to 2016 to acquire further evidence and identified 6 reports and 17 cases. The conversion rate was 11.8% (2 cases), the complication rate was 6.67% (1 case), and the preterm delivery rate was 20% (3 cases); no fetal loss was observed. Our study and literature review highlights the role of LA as a potentially feasible treatment approach for appendicitis during the third trimester.

The objective of this study was to identify preoperative factors predicting operative difficulty in patients who underwent laparoscopic cholecystectomy for acute cholecystitis within 24 hours after hospital admission. Many reports have described the superiority of performing laparoscopic cholecystectomy in the early phase of acute cholecystitis. Recently, even earlier cholecystectomy within 24 hours after hospital admission has been recommended. However, the factors that influence surgical difficulty in this patient population have not been well scrutinized. We analyzed patients who underwent laparoscopic cholecystectomy for acute cholecystitis within 24 hours of hospital presentation from 2007 to 2015. The primary outcome was the operation time. We also analyzed the amount of blood loss and the rate of conversion to open surgery. Seventy-three patients were enrolled. Mean age at surgery was 66 ± 16 years, and 52 patients were male. The mean operation time was 128 ± 59 minutes. Body mass index ≥25 kg/m2 [odds ratio (OR) = 3.6; 95% confidence interval (CI): 1.4–30.9] and dirty fat sign on preoperative computed tomography (OR = 5.3; 95% CI: 1.0–34.2) were significantly associated with increased operative time. Dirty fat sign was also significantly associated with increases in the amount of blood loss and conversion rate. Surgery should be performed more carefully in patients with these risk factors in laparoscopic cholecystectomy for acute cholecystitis performed within 24 hours of hospital presentation.

For hepatocellular carcinoma (HCC), the superiority of anatomical resection (AR) over non-anatomical resection (NR) is still controversial. In this study, we assessed the potential benefits of AR for HCC.We enrolled 173 consecutive patients with HCC who underwent hepatectomy in our hospital from August 2003 to May 2013 and compared the outcomes for the AR group (n = 125) with those for the NR group (n = 48).The median observational period was 790 days. The 1- and 2-year overall survival (OS) rates were 92.1 and 85.8 %, respectively; the 1- and 2-year disease-free survival (DFS) rates were 78.2 and 63.0 %, respectively. The AR and NR groups did not significantly differ in the OS or DFS. However, the 2-year DFS was significantly better for the AR group than the NR group among HCV patients (68.2 vs. 32.2 %; P = 0.004) and patients with alpha-fetoprotein (AFP) within the normal range (20 ng/ml; 76.7 vs. 60.9 %; P = 0.031), total bilirubin0.8 mg/dl (70.8 vs. 47.0 %; P = 0.034), and tumors 2-5 cm in diameter (82.0 vs. 62.5 %; P = 0.025).If a patient is HCV-negative, has low AFP, low total bilirubin, or a tumor diameter of 2-5 cm, AR is recommended.

Background Because the thoracic esophageal carcinoma has a high metastatic rate to the upper mediastinal lymph nodes, especially along the recurrent laryngeal nerves (RLN), it is crucial to perform a complete lymphadenectomy along the RLN without complications. Although intraoperative neural monitoring (IONM) during thyroid surgery has gained widespread acceptance as a useful tool for visual nerve identification, 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 Eighty-seven patients who underwent prone esophagectomy between December 2009 and September 2017 were included in this study. We divided patients into two groups: neural monitoring group (Nm, n = 31) and conventional method group without IONM (Cm, n = 56). We first dissect around the esophagus, preserving the membranous structure; mesoesophagus, which contains tracheoesophageal artery; RLN; and lymph nodes (mesenterization). In Nm group, we next identify the location of the RLN, which runs in the mesoesophagus using IONM before visual contact. Next, we perform lymphadenectomy around the RLN, preserving the nerve itself. Early surgical outcomes were retrospectively compared between two groups. Results In all 31 cases in the Nm group, we detected the location of the RLN before the visual contact. The sensitivity and specificity of the IONM to detect the RLN paralysis were 67% and 96%, respectively. Postoperative RLN paralysis was observed in 3 cases in the Nm group (9.7%), which was lower than that in the Cm group (32.1%, p = 0.03). Clavien-Dindo grade 2 and over aspiration were seen in 2 (Nm, 6.5%) and 16 (Cm, 28.6%) cases (p = 0.01), respectively. The postoperative hospital stay was shorter in the Nm group (22 days, median) than in the Cm group (39 days, median, p = 0.0002). The number of dissected mediastinal lymph nodes was similar in both groups (25 vs. 20, median, p = 0.12). Conclusions The combination of IONM and the concept of the mesoesophagus have substantial advantages in allowing accurate and safe mediastinal lymphadenectomy during prone esophagectomy.

Acute appendicitis is the most common general surgical problem encountered during pregnancy. Laparoscopic appendectomy (LA) is widely accepted as a minimally invasive procedure for acute appendicitis. However, LA during the third trimester is associated with problems, including technical difficulty, risk of preterm delivery, and fetal loss. We successfully managed three cases of LA during the third trimester between 2011 and 2016. None of the cases required conversion to an open procedure, and none of the patients had postoperative complications and/or fetal loss. We reviewed the literature using the PubMED database from 2007 to 2016 to acquire further evidence and identified 6 reports and 17 cases. The conversion rate was 11.8% (2 cases), the complication rate was 6.67% (1 case), and the preterm delivery rate was 20% (3 cases); no fetal loss was observed. Our study and literature review highlights the role of LA as a potentially feasible treatment approach for appendicitis during the third trimester.

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．

Although 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. Patients 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. The 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. Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

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.

食道切除手術後の低栄養状態は, 合併症発生に重大な影響を及ぼすため, 早期の経腸栄養が望ましいが, 減圧用胃管と経管栄養チューブを同時に経鼻留置するのは困難である. そこでわれわれは, 経管栄養と胃管の減圧が同時に可能なdouble elementary diet tube (W-ED tube) を開発した. W-ED tubeは16Fr径, 150cm長の2重管構造で, 管腔の一方は栄養用にチューブの先端付近に開孔 (栄養孔) している. もう一方の管腔は, 60cm口側に胃管減圧用の数個の側孔 (ドレナージ孔) を持つ. これまでに食道切除後の30症例に試用したが, 早期から経管栄養が開始でき, 良好な経過であった. 術後縫合不全のため長期間中心静脈栄養されていた症例でも, 栄養状態の改善と減圧により, 速やかに瘻孔が閉鎖できた. 結語 : 食道切除後の早期経腸栄養と吻合部の減圧のためにW-ED tubeは有用であると考えられた.

Background Incisional surgical site infection (SSI) is one of the most frequent complications that occur after colorectal surgery. Surgery for colorectal perforation carries an especially high risk of incisional SSI because fecal ascites contaminates the incision intraoperatively, and in patients who underwent stoma creation, the incision is located near the infective origin and is subject to infection postoperatively. Although effectiveness of the preventive SSI bundle of elective colorectal surgery has been reported, no study has focused exclusively on emergency surgery for colorectal perforation. Methods Patients with colorectal perforation who underwent emergency surgery and stoma creation from 2010 to 2015 at our center were consecutively enrolled in the study. In March 2013, we developed the preventive incisional SSI bundle for patients with colorectal perforation undergoing stoma creation. The effectiveness of the bundle in these patients was determined and the rates of incisional SSI between before and after March 2013 were compared. Results We enrolled 108 patients with colorectal perforation who underwent emergency operation during the study period. Thirteen patients were excluded because they died within 30 days after surgery, and 23 patients without stoma were excluded; thus, 72 patients were analyzed. There were 47 patients in the pre-implementation group and 25 patients in the post-implementation group. The rate of incisional SSI was significantly lower after implementation of preventive incisional SSI bundle (43 % vs. 20 %, p = 0.049). Postoperative hospital stay was significantly shorter after implementation of the bundle (27 vs. 18 days respectively; p = 0.008). Conclusions The preventive incisional SSI bundle was effective in preventing incisional SSI in patients with colorectal perforation undergoing emergency surgery with stoma creation.

Introduction Even after surgery and intensive postoperative management, the mortality rate associated with colorectal perforation is high. Identification of mortality markers using routinely available preoperative parameters is important. Methods We enrolled consecutive patients with colorectal perforation who underwent operations from January 2010 to January 2015. We divided them into a mortality and survivor group and compared clinical characteristics between the two groups. Additionally, we compared the mortality rate between different etiologies: malignant versus benign and diverticular versus nondiverticular. We used the χ2 and Mann–Whitney U tests and a logistic regression model to identify factors associated with mortality. Results We enrolled 108 patients, and 52 (48 %) were male. The mean age at surgery was 71 ± 13 years. The postoperative mortality rate was 12 % (13 patients). Multivariate logistic regression analysis showed that a high patient age (odds ratio [OR], 1.09; 95 % confidence interval [CI], 1.020–1.181) and low preoperative systolic blood pressure (OR, 0.98; 95 % CI, 0.953–0.999) were independent risk factors for mortality in patients with colorectal perforation. In the subgroup analysis, there was no significant difference between the malignant and benign group (11.8 % vs. 23.9 %, respectively; p = 0.970), while the diverticular group had a significantly lower mortality rate than the nondiverticular group (2.6 % vs. 17.1 %, respectively; p = 0.027). Conclusions Older patients and patients with low preoperative blood pressure had a high risk of mortality associated with colorectal perforation. For such patients, operations and postoperative management should be performed carefully.

For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy.We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28).One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008).For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.

A 7 1-year-old man presented to our hospital with constipation and abdominal pain. Computed tomography of the abdomen and colonoscopy revealed advanced cancer of the transverse colon. The biopsy specimen indicated a highly differentiated adenocarcinoma. The patient underwent extended right hemicolectomy with regional lymph node dissection. Pathological examination showed a neuroendocrine carcinoma (NEC) with concurrent adenocarcinoma of the transverse colon and regional lymph node metastases of the NEC and adenocarcinoma. The histopathological examination confirmed a diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) in accordance with the 2010 WHO Classification of Tumors of the Digestive System. Liver and lung metastases were identified 8 months after the surgery. We administered chemotherapy including 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX) plus bevacizumab, with limited therapeutic effect, as the disease progressed despite treatment. The patient chose best supportive care 13 months after the surgery. Several studies have reported that most patients with adenoendocrine cell carcinoma, including MANEC, experience relapse within 1 year after surgery, and few patients remain disease-free for long periods after surgery. The optimal strategy for the management of MANEC is variable owing to its rarity; only 2 cases of MANEC in the colon, including the present case, have been reported in Japan. It is thus important to gather more evidence on this disease and its management.

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.

症例は82歳,男性.血清アミラーゼ値上昇の原因精査のため当院へ紹介となった.腹部超音波検査,腹部造影CT検査,超音波内視鏡検査にて膵体部に約1cmの腫瘤性病変とその尾側の膵管拡張を認めた.内視鏡的逆行性膵管造影検査では,膵管は膵体部にて途絶していた.膵体部癌の診断のもと,尾側膵亜全摘を行った.病理組織学的検査では,高分化型管状腺癌, intermediate type, INFβ, ly1, v0, ne0, mpd(+)14mm, Pb, TS1: 9mm, nodular type, RP(+), T3, N1 (11p, 1/16個), M0, Stage IIIであった.主膵管内進展は膵頭部の方向へ14mmに及んだ.小膵癌症例に対しても,リンパ節郭清を伴ったいわゆる標準手術によりR0を目指し,膵切離に際しては術中迅速病理検査による膵管断端の確認が必要と思われる.

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.

乳癌症例においてICG蛍光測光を用いて乳腺リンパ流路を観察し,センチネルリンパ節生検 (SNB) への応用を試みた. 2004年7月から11月の乳癌初回手術39例41乳房を対象とし,乳輪皮内にICG液を注入後,励起光を照射しCCDカメラにてリンパ流路を蛍光イメージとして観察し, SNBへの応用も試みた. 1) リンパ流路:腋窩方向へのリンパ流は88%,胸鎖関節方向へは27.5%,乳腺外側方向へは30%,傍胸骨方向へは32%に認められた. 2) 35乳房でSNBを施行した.腋窩小切開部位で蛍光を発する染色リンパ節を確認しセンチネルリンパ節とした.染色が軽度で脂肪織内に埋没していても,蛍光イメージの観察から容易にリンパ節を同定でき,同定率は94.3% (33/35) であった. ICG蛍光測光では乳房における多方向へのリンパ流が観察されリンパ節の同定が容易であり,色素法によるSNBの欠点を補う有用な方法と思われる.

Though the outcome of resection for locally invasive pancreatic cancer is still poor, it has gradually improved in Japan, and the 5-year survival is now about 10%. However, the advantage of resection over radiochemotherapy has not yet been confirmed by a randomized trial. We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter randomized design.Patients with pancreatic cancer who met our preoperative criteria for inclusion (pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery, or without distant metastasis) underwent laparotomy. Patients with operative findings consistent with our criteria were randomized into a radical resection group and a radiochemotherapy group (200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy) without resection. The 2 groups were compared for mean survival, hazard ratio, 1-year survival, quality of life scores, and hematologic and blood chemical data.Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group. There was 1 operative death. The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival (62% vs 32 %, P=.05), mean survival time (17 vs 11 months, P.03), and hazard ratio (0.46, P=.04). There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection.Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection.

Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to-mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)β, and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.

Many cancers are resistant to Fas-mediated apoptosis despite the expression of Fas. To investigate the mechanisms by which Fas signals are attenuated, we focused on decoy receptor 3 (DcR3). DcR3 is a soluble receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily and overexpresses in some forms of cancers. Exogenous DcR3 inhibits Fas-mediated apoptosis in Fas-sensitive Jurkat cells. In our study, we examined the expression and function of DcR3 in pancreatic cancers. TaqMan RT-PCR showed that DcR3 mRNA was highly expressed in pancreatic cancer cell lines (71%) and tissues (67%). Its expression significantly correlated with cancer invasion to veins. Western blotting showed that the DcR3 protein was produced and secreted in 4 of 6 cell lines. The protein expressions were compatible with the mRNA expression. Five of 7 pancreatic cancer cell lines became sensitive to agonistic anti-Fas antibody (CH-11) to various extents, without Fas upregulation, when exposed to CH-11 for 48 hr after pretreatment with IFNγ. Four of 7 pancreatic cancer cell lines were inhibited from growing, compared to control cells, when cocultured with membrane-bounded Fas ligand (mFasL) transfected lymphomas for 48 hr after pretreatment with IFNγ. DcR3 reduced this growth inhibition when added exogenously. Regression analysis showed that the DcR3 expression significantly correlated with the sensitivity to mFasL, and not to CH-11. These results suggest that DcR3 is highly expressed in many pancreatic cancers and endogenous DcR3 blocks the growth inhibition signals mediated by mFasL. DcR3 can be a candidate target molecule for the therapeutic intervention. © 2003 Wiley-Liss, Inc.

In a patient with cancer of the hypopharynx and cervical esophagus reconstruction was performed with a free Sigmoid colon autograft. The feeding vessels of this autograft were anastomosed by microvascular surgery. A reconstructed esophagus made from a free Sigmoid colon has less peristalsis than one from a free jejunum. Therefore, our patient did not have swallowing difficulties after the beginning of oral feeding 2 weeks after operation. From this aspect, Sigmoid colon autografts seem to be better than jejunum autografts in the reconstruction Qf the hypopharynx and cervical esophagus.

The intravenous calcium injection test has been reported to be useful for the diagnosis of gastrinoma. However, the mechanism underlying calcium-evoked gastrin release is not fully understood. We investigated the mechanism of calcium-stimulated gastrin release from gastrinoma cells in vitro with a particular focus on the calcium-sensing receptor (CaR). Human gastrinoma cells were taken from mechanically minced gastrinoma tissues obtained at surgery. In the perifusion system, high [Ca2+]o induced gastrin release from gastrinoma cells. As [Ca2+]o increased, [Ca2+]i rapidly increased, as monitored by fluorometry. The response was not inhibited by nifedipine, a blocker of the voltage-dependent calcium channel. Reverse transcriptase-polymerase chain reaction and subsequent Southern blot hybridization revealed the presence of the CaR gene in human gastrinoma tissues. Moreover, the expression of CaR in gastrinoma tissues was confirmed by immunohistochemistry. Our results demonstrated that CaR was expressed in human gastrinoma cells and could be involved in the mechanism of calcium-evoked gastrin release.

Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin alpha(V)beta3 and acts as an angiogenic inhibitor. A novel cyclic RGD peptide, cyclo(-RGDf==V-) (f==V), was synthesized and its biological activities were characterized and compared with its analogs, cyclo(-RGDfV-) (fV) and cyclo(-RGDf-MeV-) (fMeV). It bound to integrin alpha(V)beta3 with almost the same affinity as the fV and fMeV analogs. All three compounds inhibited the adhesion and growth of HUVEC cells in a dose-dependent manner in vitro. Out of three, fMeV had the strongest effect, f==V was almost as strong as fMeV, and fV had the least effect. However, in vivo, f==V significantly decreased the intratumoral microvessel density (MVD) in the DLD-1 (human colon cancer cell) inoculated mice, while fMeV had little effect. These results suggest the potential usefulness of the cyclo(-RGDf==V-) as an antiangiogenic agent for clinical use in the future.

In this study, we examined whether or not a small peptide derived from p16(INK4A) protein with the antennapedia carrier sequence could inhibit the growth of pancreatic cancer cells through the inhibition of cell cycle progression. Growth inhibition by the p16-derived peptide was observed in a time- and dose-dependent manner in AsPC-1 and BxPC-3 cells (p16-negative and pRb-positive), whereas Saos-2 cells (p16-positive and pRb-negative) showed no inhibitory effect. In AsPC-1 and BxPC-3 cells, the proportion of cells in the G(1) phase markedly increased 48 h after treatment with 20 microM p16-derived peptide. Cell-cycle analysis of Saos-2 cells showed little change during the entire period of treatment. Immunoblot analysis showed inhibition of pRb phosphorylation after treatment of BxPC-3 with 10 microM p16 peptide. Furthermore, the p16 peptide caused a decrease in cyclin A at later times of treatment. These results demonstrate that the p16-derived peptide can inhibit the growth of p16-negative and pRb-positive pancreatic cancer cells by means of G(1) phase cell cycle arrest resulting from the inhibition of pRb phosphorylation. Restoration of p16/pRb tumor-suppressive pathway by re-expression of p16(INK4A) may play a therapeutic role in the treatment of pancreatic cancer.

Background. The Japanese Pancreas Society Registry Committee obtained data on 16 071 patients with pancrea-tic cancer diagnosed from 1981 to 1996. This is the largest multi-institutional retrospective study of the Japanese experience to describe the extent of disease and survival.

BACKGROUND Positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) has been used for the evaluation of various tumors, but accumulation in inflammatory lesions makes it a controversial modality. The aim of this study was to investigate the usefulness of delayed scanning in differentiation between malignant and benign lesions in the pancreas. METHODS Forty-seven patients with suspected pancreatic carcinoma were studied by FDG-PET. All patients received approximately 370 megabequerels of FDG after a transmission scan, and an emission scan was performed 1 hour and 2 hours later for all patients. A subset of 19 patients was also scanned at 3 hours postinjection. The standardized uptake value (SUV) was determined, and the retention index was calculated by dividing the increase in the SUV between 1 hour and 2 hours postinjection by the SUV at 1 hour postinjection. RESULTS Of 27 malignant lesions, the SUVs of 22 lesions increased at 2 hours postinjection, whereas the FDG uptake in 17 of 20 benign lesions decreased. The SUVs at 3 hours postinjection were higher than those at 2 hours postinjection in 9 of 14 malignant lesions and in 2 of 5 benign lesions. Malignant lesions showed a higher retention index than benign lesions (mean ± standard deviation: 12.36 ± 13.37 and −7.05 ± 17.28, respectively; P < 0.0001). Applying an SUV of 2.5 at 1 hour postinjection with the cut-off value for the differentiation between malignant and benign lesions caused one false negative result and seven false positive results, with a diagnostic accuracy of 83.0% (39 of 47 patients). However, combining the retention index with the SUV obtained at 2 hours postinjection provided a higher diagnostic accuracy (91.5%; 43 or 47 patients) than the SUV alone. The false negative rate remained constant when the retention index was taken into account. Images at 3 hours postinjection usually were unhelpful in differentiating further between malignant lesions and benign lesions. CONCLUSIONS The current data suggest that delayed FDG-PET scanning at 2 hours postinjection may contribute to differentiation between malignant and benign lesions in the pancreas. Cancer 2000;89:2547–54. © 2000 American Cancer Society.