佐田 尚宏

We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n = 1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19-9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words).

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are primary pancreatic neoplasms that can act as precursors to invasive adenocarcinoma of the pancreas. The peritumoral stroma has been increasingly recognized to play an important role in many types of tumors. Therefore, to investigate the clinicopathological significance of the peritumoral stroma in IPMNs, we examined the histological features of the peritumoral stroma in each subtype and histological grade of IPMNs. Eighty-two patients with IPMN, who underwent surgical resection, were reviewed clinicopathologically. Intraductal papillary mucinous neoplasms (86 lesions in total) were histologically subclassified into gastric (n = 51), intestinal (n = 22), pancreatobiliary (n = 11), and oncocytic (n = 2) subtypes. Peritumoral histological features between the gastric and intestinal subtypes were evaluated by each histological grade. The results showed that subepithelial edema and inflammatory cell infiltration were more commonly observed in the gastric subtype (74% and 79%, respectively) than in the intestinal subtype (12% and 25%, respectively) of low-grade IPMNs. On the other hand, mucus lakes were more commonly observed in the intestinal subtype (100%) than in the gastric subtype (0%) of high-grade IPMNs. In addition, pancreatobiliary subtype IPMNs tended to exhibit acute inflammation such as neutrophil predominance. This study showed that peritumoral histological features differed among subtypes of IPMNs from low-grade tumors. These differences suggest the possibility that each subtype of IPMNs has a distinct mechanism from an early stage of tumor progression, which is reflected in the properties of the peritumoral stroma.

OBJECTIVES: In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required. METHODS: Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. RESULTS: The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. CONCLUSIONS: After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed.

It has been suggested that total cholesterol levels and the use of statin medications are associated with the incidence of complications after gastrointestinal surgery. The aim of this study was to determine if preoperative total cholesterol levels are associated with a higher risk of postoperative infections and mortality. A total of 2211 patients undergoing general surgical procedures between December 2006 and November 2008 at Iizuka Hospital and between January 2010 and March 2012 at Jichi Medical University Hospital were reviewed. Multiple logistic regression models were used to evaluate serum total cholesterol and other variables as predictors of postoperative nosocomial infections. Serum total cholesterol concentrations lower than 160 mg/dl were associated with an increased incidence of superficial and deep incisional surgical site infections. Serum total cholesterol levels showed a reverse J-shaped relationship with the development of organ space surgical site infection and pneumonia. There was no discernible effect of serum cholesterol levels on the postoperative mortality observed in this cohort of patients. Decreased serum albumin was one of the strongest risk factors for the development of nosocomial infection after surgery. Postoperative pneumonia was not observed in patients taking statin medications whose cholesterol levels were <200 mg/dl. Serum total cholesterol may be a valid predictor of surgical outcome. Preoperative statin use may affect the development of postoperative pneumonia in patients with total cholesterol levels below 200 mg/dl.

PURPOSE: We hypothesized that a reduction in the size of the lymph nodes after neoadjuvant therapy for locally advanced rectal carcinoma would be associated with decreased lymph node metastases and/or a better prognosis. METHODS: Between March 2006 and April 2012, 71 patients with primary rectal cancer received neoadjuvant chemoradiation therapy (CRT). For all lymph nodes 5 mm or larger in size, the major and minor axes were measured on CT scan images, and the product was calculated. The lymph node size was determined before and after CRT. The patients were divided into three groups based on the lymph node size before and after treatment. Group A exhibited a reduction in size of 60% or more, Group B a reduction of less than 60% and Group C had no lymph node enlargement before treatment. RESULTS: The incidence of lymph node metastases on pathological examination was 15% in Group A and 50% in Group B (p = 0.006). The five-year disease-free survival in Group A was 84% compared with 78% in Group B (log rank p = 0.34). The five-year overall survival in Group A was 92% compared with 74% in Group B (log rank p = 0.088). CONCLUSIONS: A reduction in the size of enlarged lymph nodes after neoadjuvant therapy may be a useful prognostic factor for recurrence and survival.

BACKGROUND: Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines. METHODS: A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines. RESULTS: Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles. CONCLUSIONS: The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html.

We report a rare case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis without other organ involvement. A 69-year-old-man was referred for the evaluation of jaundice. Computed tomography revealed thickening of the bile duct wall, compressing the right portal vein. Endoscopic retrograde cholangiopancreatography showed a lesion extending from the proximal confluence of the common bile duct to the left and right hepatic ducts. Intraductal ultrasonography showed a bile duct mass invading the portal vein. Hilar bile duct cancer was initially diagnosed and percutaneous transhepatic portal vein embolization was performed, preceding a planned right hepatectomy. Strictures persisted despite steroid therapy. Therefore, partial resection of the common bile duct following choledochojejunostomy was performed. Histologic examination showed diffuse and severe lymphoplasmacytic infiltration, and abundant plasma cells, which stained positive for anti-IgG4 antibody. The final diagnosis was IgG4 sclerosing cholangitis. Types 3 and 4 IgG4 sclerosing cholangitis remains a challenge to differentiate from cholangiocarcinoma. A histopathologic diagnosis obtained with a less invasive approach avoided unnecessary hepatectomy.

BACKGROUND: Although advanced esophageal squamous-cell carcinoma (ESCC) is treated using a multidisciplinary approach, outcomes remain unsatisfactory. The microenvironment of cancer cells has recently been shown to strongly influence the biologic properties of malignancies. We explored the effect of supernatant from esophageal fibroblasts on the cell growth and chemo-resistance of ESCC cell lines. METHODS: We used 22 ESCC cell lines, isolated primary human esophageal fibroblasts and immortalized fibroblasts. We first examined cell proliferation induced by fibroblast supernatant. The effect of supernatant was evaluated to determine whether paracrine signaling induced by fibroblasts can influence the proliferation of cancer cells. Next, we examined the effects of adding growth factors HGF, FGF1, FGF7, and FGF10, to the culture medium of cancer cells. These growth factors are assumed to be present in the culture supernatants of fibroblasts and may exert a paracrine effect on the proliferation of cancer cells. We also examined the intrinsic role of HGF/MET and FGFs/FGFR in ESCC proliferation. In addition, we examined the inhibitory effect of lapatinib on ESCC cell lines and studied whether the fibroblast supernatants affect the inhibitory effect of lapatinib on ESCC cell proliferation. Finally, we tested whether the FGFR inhibitor PD-173074 could eliminate the rescue effect against lapatinib that was induced by fibroblast supernatants. RESULTS: The addition of fibroblast supernatant induces cell proliferation in the majority of cell lines tested. The results of experiments to evaluate the effects of adding growth factors and kinase inhibitors suggests that the stimulating effect of fibroblasts was attributable in part to HGF/MET or FGF/FGFR. The results also indicate diversity in the degree of dependence on HGF/MET and FGF/FGFR among the cell lines. Though lapanitib at 1 μM inhibits cell proliferation by more than 50% in the majority of the ESCC cell lines, fibroblast supernatant can rescue the growth inhibition of ESCC cells. However, the rescue effect is abrogated by co-treatment with FGFR inhibitor. CONCLUSION: These results demonstrate that cell growth of ESCC depends on diverse receptor tyrosine kinase signaling, in both cell-autonomous and cell-non-autonomous manners. The combined inhibition of these signals may hold promise for the treatment of ESCC.

CONTEXT: Insulinomas, which are generally smaller than 2 cm, may be difficult to detect by routine imaging modalities including abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although preoperative detection of insulinomas is essential for operative planning, it is often challenging due to their small size. While arterial stimulation and venous sampling has been used in patients with insulinomas it has been largely supplanted by early-phase thin-slice computed tomography. CASE REPORT: We report three patients with insulinomas, which were not detected by routine computed tomography scan, but were successfully imaged using early-phase thin-slice computed tomography. Enucleation was performed in all patients based on preoperative imaging. All three patients had an unremarkable postoperative course. CONCLUSION: Early-phase thin-slice computed tomography is recommended for the preoperative identification of insulinomas. This non-invasive imaging technique should be considered before performing arterial stimulation and venous sampling.

INTRODUCTION: Gastric outlet obstruction is characterized by the retention of gastric contents. Removal of gastric contents is an important part of the treatment strategy. The use of a nasogastric tube alone can result in inadequate removal of gastric contents. We treated a patient with advanced gastric cancer and gastric outlet obstruction with pancrelipase to aid in the removal of gastric contents. PRESENTATION OF CASE: The patient is an 81-year-old man with a Type 3 gastric cancer nearly circumferentially involving the antrum, resulting in gastric outlet obstruction. A nasogastric tube was placed for four days, but drainage of gastric contents was inadequate. Pancrelipase was then given orally for four days, and gastric contents were evacuated. The patient underwent distal gastrectomy with Roux-en-Y reconstruction and was discharged from the hospital on postoperative day 14. DISCUSSION: This report suggests that pancrelipase may be beneficial in the treatment of patients with gastric outlet obstruction. CONCLUSION: Pancrelipase allowed gastric contents to be evacuated in a short period of time in a patient with gastric outlet obstruction.

INTRODUCTION: Radical resection of bile duct carcinoma may require resection of hepatic arteries. Preoperative segmental embolization of the hepatic artery for resection of hilar cholangiocarcinoma has been reported. We report a patient with bile duct carcinoma infiltrating the proper hepatic artery. PRESENTATION OF CASE: A 66-year old male with jaundice was diagnosed with mid-distal bile duct carcinoma. A replaced left hepatic artery originated from the left gastric artery. Pylorus-preserving pancreaticoduodenectomy (PPPD) with combined resection of hepatic artery was planned. To promote the development of collateral blood flow after excision of the hepatic artery, preoperative segmental embolization of the proper hepatic artery was performed. The patient underwent PPPD with concurrent resection of the common hepatic, right hepatic, and middle hepatic arteries without arterial reconstruction. He received adjuvant chemotherapy with gemcitabine for six months and is alive three years after surgery without tumor recurrence. DISCUSSION: The growth of collateral vessels after selective embolization of the proper hepatic artery has been used for hilar lesions and bile duct lesions. Resection of the hepatic artery without the need for complex arterial reconstruction, allowing a radical resection, may have contributed to this patient's relatively unremarkable recovery and long-term survival. Retroperitoneal mobilization of the pancreatic head and duodenum must be limited as important collaterals may originate in that area. CONCLUSION: Preoperative segmental embolization of the hepatic artery before PPPD for a patient with a replaced left hepatic artery encouraged the growth of collateral blood supply, allowing radical resection including the vessels and obviated the need for arterial reconstruction.

INTRODUCTION: We report a patient with a rapidly progressing recurrence of hepatocellular carcinoma (HCC) with a portal vein tumor thrombus after radiofrequency ablation of the original lesion, then treated with transcatheter arterial infusion. Radical hepatic resection demonstrated a complete pathological response. PRESENTATION OF CASE: A 60-year old male with alcoholic cirrhosis and gastric varices was diagnosed with HCC measuring 12mm in segment 8. He underwent laparoscopic radiofrequency ablation, but recurred three months later. The lesion progressed rapidly and the right portal vein was occluded. He then underwent transcatheter arterial infusion with miriplatin and iodized oil, which was effective in reducing the size of the main lesion and portal vein tumor thrombus. Right anterior sectionectomy was then performed. Pathologically, there were no viable HCC cells in either the main lesion or the portal vein thrombus. He is alive two years and nine months after surgery without recurrence. DISCUSSION: A rapidly progressing HCC recurrence with portal vein tumor thrombus is usually associated with a poor prognosis. No effective treatments have been reported in this situation except hepatic resection. In this patient the tumor was effectively reduced after three courses of transarterial miriplatin and subsequent radical hepatic resection. This is the first report to achieve a complete pathological response for such an aggressive recurrence after initial radiofrequency ablation. CONCLUSION: This strategy may result in long-term survival of patients with rapidly progressing recurrent HCC with portal vein thrombus, and further study is warranted.

PURPOSE: Ghrelin may lead to weight gain by appetite stimulation. This prospective study investigated the association between weight loss and the ghrelin levels in patients after gastrectomy. METHODS: Thirty-three males and eight females were enrolled in the study. The average age was 66 years. Measurements of the serum ghrelin level and an appetite questionnaire were performed preoperatively and at one, three, six and 12 months postoperatively. RESULTS: The preoperative serum total ghrelin level was 51.6 ± 31.9 (fmol/ml ± SD), and that at one, three, six and 12 months postoperatively was 16.9 ± 9.0, 21.2 ± 16.0, 28.0 ± 19.1 and 29.6 ± 20.6 (fmol/ml ± SD), respectively. The appetite score was 2.02 ± 1.09 points at 1 month, and increased significantly to 2.61 ± 1.00 by 12 months. CONCLUSIONS: The ghrelin levels were reduced after gastrectomy and did not recover by 12 months postoperatively. Further studies are needed to evaluate these results as the basis of a therapeutic trial.

アルコール摂取(多飲)は急性膵炎、慢性膵炎の成因として最も頻度が高い。他の成因と異なり、アルコール性膵炎は断酒・禁煙で発症・進展の予防が可能で、生活指導が重要な疾患である。その一方で「アルコール性」を規定するエタノール摂取量の明確な基準はなく、その発症・進展の機序についても不明な点が多い。慢性膵炎臨床診断基準2009では慢性膵炎をアルコール性と非アルコール性に分類し、発症前、発症早期に治療介入ができるように慢性膵炎疑診、早期慢性膵炎の診断基準を設定した。急性膵炎でも高リスク群であるアルコール多飲者の実際の発症率は低率で、遺伝子異常(SPINK1、PRSS1など)など、他の要因が深く関与していることが想定されている。アルコール性急性膵炎、慢性膵炎の診断・治療は、他の成因によるものと大きく変わるところはなく、介入治療は改訂アトランタ分類2012による膵炎局所合併症の新分類に応じた適切な時期・手技で行うことが推奨される。(著者抄録)

A 54-year-old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin-producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high-grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.

BACKGROUND: The sentinel lymph node (SLN) biopsy technique using superparamagnetic iron oxide (SPIO) as a tracer instead of radioisotopes has been described. To further advance this technique, we evaluated preoperative SPIO-MR sentinel lymphography to facilitate the accurate identification of the lymphatic pathways and primary SLN. METHODS: A prospective study was performed in ten patients with breast cancer and clinically negative axillary lymph nodes. None of the patients received preoperative chemotherapy. After 1.6 ml of SPIO (ferucarbotran) was injected in the subareolar breast tissue, sentinel axillary lymph nodes were detected by MRI in T2*-weighted gradient echo images and resected using the serial SPIO-SLN biopsy procedure with a handheld magnetometer. RESULTS: In one patient, gadolinium-enhanced MR imaging was performed at the same time as SPIO-MR lymphography, and this patient was excluded from further analysis. In all patients (9/9) SLNs were detected by SPIO-MR sentinel lymphography and successfully identified at surgery. The number of SLNs detected by lymphography (mean 2.7) significantly correlated with SLNs identified at surgery (mean 2.2). One patient had nodal metastases. In one patient, skin color changed to brown at the injection site and resolved spontaneously. There were no severe reactions to the procedure or complications in any patient. CONCLUSIONS: This is the first study to evaluate SPIO both as a contrast material in MR sentinel lymphography and as a tracer in SLN biopsy using an integrated method. The acquired three-dimensional imaging demonstrated excellent image quality and usefulness to identify SLN in conjunction with SLN biopsy.

The growth, invasiveness and metastasis of human cancers are determined not only by cancer cells, but also by their microenvironment. Activated stromal fibroblasts promote tumor progression by secreting growth factors. In the present study, we focused on interrelations between cancer and fibroblasts, the main component of tumor stroma. We retrospectively analyzed the relations of mortality to clinical, pathological, and α-smooth muscle actin (α-SMA) characteristics in 97 consecutive patients with esophageal squamous cell carcinoma (ESCC). In vitro, we used TE-11, KYSE150 and KYSE220 ESCC cell lines and isolated esophageal stromal fibroblasts, some of which were immortalized. Migration assays were conducted to assess the effects of fibroblasts on cancer-cell migration and 3-dimensional organotypic cultures. In vivo, TE-11 and KYSE220 cells plus immortalized fibroblasts were co-transplanted subcutaneously in Nod/Scid mice to assess the effects of fibroblasts on tumorigenicity. Clinicopathologically, the α-SMA expression of cancer stroma was correlated with venous invasion (p<0.01), nodal involvement (p=0.02), recurrence (p=0.01), and was a predictor of survival in patients with stage I and II ESCC (p=0.04). In vitro, the presence of fibroblasts strongly promoted the migration of TE-11, KYSE150 and KYSE220 cells. On organotypic culture, stromal invasion was observed only in the presence of immortalized fibroblasts. In vivo, tumors developed or grew in a fibroblast‑dependent manner after implantation. Our findings provide evidence that stromal fibroblasts and tumor cells interact to promote tumor progression in ESCC. In patients with earlier stage ESCC, α-SMA may be a predictor of mortality. Inhibition of paracrine systems associated with tumor fibroblasts may slow or reverse tumor progression, potentially leading to the development of new targeted therapies.

BACKGROUND: The goal of this study is to examine changes in pancreatic perfusion due to pneumoperitoneum using perfusion CT in vivo. METHODS: Three pigs were studied. Under general anesthesia, pneumoperitoneum was induced to 16 mm Hg. Perfusion CT scans were acquired at a rate of 1 image per 2 seconds for 60 seconds. Scans were repeated 5 days later without pneumoperitoneum using the same protocol, in the same animals. The time density curve, color map, peak enhancement, time to peak, blood flow, blood volume, and permeability were evaluated. RESULTS: In the presence of pneumoperitoneum, peak enhancement in radiodensity was decreased and time to peak was increased, and both blood flow and blood volume decreased. However, there was no consistent change in permeability observed. CONCLUSION: This study demonstrates that pneumoperitoneum quantitatively results in decreased blood flow and blood volume to the pancreas in an in vivo animal model.

A 41-year-old woman was admitted with upper abdominal pain, vomiting and fever. Abdominal CT scan showed a colo-duodenal fistula with inflammatory thickening of the transverse colon. The patient's general health was poor because of hypoalbuminemia and coagulopathy. Endoscopy showed a fistula at the lower duodenal angle and the stomach was filled with refluxed stool. Ileostomy and percutaneous endoscopic gastrostomy were performed at that time and a double lumen gastro-jejunostomy inserted through the gastrostomy to allow both gastric drainage and distal enteral feeding. Nutrition support was gradually converted from parenteral to enteral feeding. Colonoscopy showed stenosis of the transverse colon with a colo-colonic fistula near the stenosis. Two months later, right hemi-colectomy and closure of the colo-duodenal fistula were performed. The resected specimen showed stenosis and a fistula in the transverse colon due to Crohn's disease. The colo-colonic fistula was present and the colo-duodenal fistula had almost closed due to fibrosis. The postoperative course was uneventful and the patient was discharged after administration of infliximab. Use of a double lumen gastro-jejunostomy tube was effective in improving the patient's general condition. This therapeutic strategy allowed the safe conduct of major resection in a high-risk patient.

Rational treatment for neoplasms of the duodenal papilla (NDPs) is still controversial, especially for early stage lesions. Total papillectomies are indicated in patients expected to have adenomas, adenocarcinoma in an adenoma, or mucosal adenocarcinomas with no lymph node metastases. However, the preoperative pathological evaluation of NDPs is still challenging and often inaccurate, mainly because of the complicated anatomical structures involved and the possibility of an adenocarcinoma in an adenoma. Herein, we introduce a new method of total papillectomy, the extraduodenal papillectomy (ExDP). In this method, papillectomy is undertaken from outside of the duodenum, instead of resection from the inside through a wide incision of the duodenal wall as is done in conventional transduodenal papillectomy (TDP). The advantages of ExDP are precise and deeper cutting of the sphincter and shorter exploration time of the tumor compared to conventional TDP. We demonstrate three representative patients, all of whom had an uneventful postoperative course. One of them subsequently underwent a pylorus preserving pancreatoduodenectomy after detailed postoperative pathological evaluation. Including that patient, no recurrence has occurred with 37-46 months of follow-up. In conclusion, ExDP is regarded as a "total biopsy" for early stage borderline lesions and a feasible, less demanding alternative method for the treatment of NDPs.

症例は66歳の女性で，嘔吐と体重減少を主訴に当院を受診した．腹部CTにて十二指腸周囲，肝十二指腸間膜，小網に至る気腫像，胃十二指腸下行脚部の著明な拡張，水平脚部のcaliber changeを認めた．さらに，多量の腹腔内free airと十二指腸周囲の後腹膜ガス像も認めたため，上腸間膜動脈症候群による腸管気腫症および上部消化管穿孔の診断で緊急手術を施行した．術中所見では胃十二指腸の拡張，および十二指腸気腫を認めたが穿孔所見や腹水は認めなかった．経胃腸瘻造設のみ行い，術後経過は良好であった．腸管気腫症の原因は多岐にわたり，時にfree airを伴い消化管穿孔との鑑別が困難なことがある．患者の臨床所見と腸管気腫症の成因を詳細に検討し治療方針を決定することが重要で，審査腹腔鏡も選択肢の一つと考えられた．

Purpose: This retrospective study evaluates the clinical course and outcomes of patients who underwent surgery for strangulated hernias. Methods: Among 520 groin hernias from 2001 to 2012, 51 inguinal and 42 femoral hernias were strangulated and operated emergently at a tertiary referral center. Perioperative factors, patient profiles, and time interval to surgery (Ttotal = time from onset to surgery, T1 = time from onset to initial evaluation, T2 = time from the first hospital to the tertiary center, T3 = time from admission at the tertiary center to surgery, Ttotal = T1 + T2 + T3) were analyzed in patients with strangulation, then compared between two groups, the bowel resection (BR) group and the non-bowel resection (NBR) group. Results: T1, T2 and Ttotal in the bowel resection group were significantly longer than those in the non-bowel resection group (P &lt  0.05). Patients who presented initially to the tertiary center (T2 = 0) had a significantly lower resection rate than patients transported from other hospitals (24 vs. 44 %, P = 0.048). There was no significant difference in morbidity between the BR and NBR groups (35 vs. 24 %, P = 0.231). Conclusions: The elapsed time from onset to surgery, especially T1 and T2, is the most important prognostic factor in patients with strangulated groin hernias. Early diagnosis and transportation are essential for good outcomes.

Pancreatic islet transplantation has received widespread attention as a promising treatment for type 1 diabetes. However, islets for transplantation are subject to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here we found that protein fractions secreted by mesenchymal stem cells (MSCs) were capable of activating preserved islets. A conditioned medium from the supernatant obtained by culturing adipose tissue MSCs (derived from wild-type Lewis rats) was prepared for 2 days in serum-free medium. Luc-Tg rat islets to which an organ preservation solution was added were then incubated at 4°C with fractions of various molecular weights prepared from the conditioned medium. Under the treatment with some of the fractions, by 4 days the relative luminescence intensities (representative of the ATP levels of the cold-preserved islets) had increased to over 150% of their initial values. Our novel system may be able to restore isolated islets to the condition they were in before transport, culture, and transplantation.

BACKGROUND: The double-stapling technique (DST) for esophagojejunostomy using the transorally inserted anvil (OrVil; Covidien Japan, Tokyo, Japan) is one of the reconstruction methods used after laparoscopy-assisted total gastrectomy (LATG). This technique has potential advantages in terms of less invasive surgery without the need to create a complicated intraabdominal anastomosis. METHODS: From 2008 to 2011, 262 patients with gastric cancer underwent total gastrectomy and reconstruction with a Roux-en-Y anastomosis, and 52 patients underwent LATG with DST. A retrospective analysis then was performed comparing the patients who experienced postoperative stenosis after LATG-DST (positive group) and the patients who did not (negative group). A comparative analysis was performed among patients comparing conventional open total gastrectomy and LATG, and multivariate analysis was performed to evaluate risk factors for the development of anastomotic stenosis. RESULTS: A minor leak was found in 1 patient (1.9 %), and 11 patients experienced anastomotic stenosis (21 %) after LATG with DST. Among the patients with anastomotic stenosis, three (3/4, 75 %) anastomoses were performed with the 21-mm end-to-end anastomosis (EEA) stapler, and eight anastomoses were performed (8/47, 17 %) with the 25-mm EEA stapler. The median interval to the diagnosis of anastomotic stenosis was 43 days after surgery. The patients with stenosis needed endoscopic balloon dilation an average of four times, and the rate of perforation after dilation was 13 %. The clinical and operative characteristics did not differ between the two groups. Anastomotic stenosis after open total gastrectomy occurred in two cases (0.98 %). Multivariate analysis showed that the size of the EEA stapler and the use of DST were risk factors for anastomotic stenosis. CONCLUSION: Esophagojejunostomy using DST with OrVil is useful in performing a minimally invasive procedure but carries a high risk of anastomotic stenosis.

BACKGROUND: Some hospitals lack facilities for radioisotopes in sentinel node biopsy. A novel method is used with a superparamagnetic tracer and a magnetometer instead of a radioisotope. METHODS: Thirty patients were included in the study after obtaining IRB approval. Superparamagnetic iron oxide and patent blue dye were injected in the subareolar breast tissue. Following a few minutes of massage to promote migration of the iron tracer and blue dye throughout the lymphatic vessels, the axillary lymph nodes were detected transdermally using a handheld magnetometer and followed by standard axillary dissection in all patients. RESULTS: Of 30 patients evaluated, sentinel lymph nodes were identified in 90% (27/30) using both blue dye and magnetic tracer. Sentinel lymph nodes were identified using the magnetic method in 23/30 (77%) and blue dye in 24/30 (80%). There was one false-negative sentinel node, resulting in an overall sensitivity of 6/7 (86%). CONCLUSIONS: This is the first study to use a magnetic tracer to identify sentinel lymph nodes in patients with breast cancer. This new technique may alter the role of radioisotopes with further refinement and experience.

We report a case of acquired hemophilia A (AHA) after esophageal resection. The patient was an 80-year-old woman whose preoperative activated partial-thromboplastin time (APTT) was well within the normal range, at 34.9 s. She underwent thoracic esophagectomy and gastric pull-up for superficial esophageal cancer (operative time, 315 min; intraoperative blood loss, 245 ml). Intrathoracic and subcutaneous bleeding occurred spontaneously on postoperative day (POD) 39. The APTT was prolonged, at 140 s, and factor VIII inhibitor was 36 Bethesda U/ml. Treatment with recombinant activated factor VII, prednisolone, and cyclophosphamide resulted in remission within 2 months. This case supports an association between surgery and the triggering of factor VIII inhibitors. The diagnosis of AHA requires clinical acumen and must be considered in any patient with bleeding and a prolonged APTT.

We report on a 53-year-old male with esophageal cancer. He had no evidence of distant metastasis, and received a subtotal esophagectomy. Histopathologically, the tumors were contiguous with Barrett's epithelium. Undifferentiated carcinoma components existed independently of differentiated adenocarcinoma components. Undifferentiated carcinoma was present proximal to the esophagogastric junction. Both tumors had invaded the submucosa and were associated with a prominent lymphoid stroma. Metastasis from undifferentiated carcinoma was found in the paraesophageal lymph nodes. Immunohistochemically, both components were negative for 34bE12 and positive for CAM5.2 and showed nearly identical staining patterns for p53, indicating that the tumors were derived from Barrett's epithelium. Because the undifferentiated carcinoma did not express CK20 or carcinoembryonic antigen, the properties of adenocarcinoma had apparently been lost during the process of tumor cell progression. This is the first report of undifferentiated carcinoma associated with Barrett's esophagus with adenocarcinoma.