Search

A 64-year-old female received modified FOLFOX6 therapy with continuous administration of a high concentration of 5-fluorouracil (5-FU) for recurrence of peritoneal dissemination after total gastrectomy. Twenty-nine hours after the administration, there was the sudden onset of altered consciousness and hepatic dysfunction accompanied by hyperammonemia. The consciousness and hepatic function improved the following day after treatment with branched-chain amino acid formulation, lactulose, fresh frozen plasma, and continuous hemodiafiltration. Thus, the diagnosis was 5-FU-induced hyperammonemia. Improvement of dehydration and renal dysfunction would be important for avoiding the risk of developing the side effects. Because recurrent gastric cancer is often a progressive condition, post-treatment might be promptly transferred to the other posterior regimen without 5-FU as required.

BACKGROUND Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2 = 0.870, 90% CI: 0.768-0.972). CONCLUSION The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

Objective: IgG4-related sclerosing cholecystitis is generally associated with IgG4-related sclerosing cholangitis and presents with diffuse, circumferential thickening of the gallbladder wall. We report a rare case of localized IgG4-related sclerosing cholecystitis without IgG4-related sclerosing cholangitis, which was difficult to differentiate from gallbladder cancer preoperatively. Patient: A 56-year-old man with suspected IgG4-related disease or gallbladder cancer was admitted to our ward. The serum IgG4 level was elevated at 721 mg/dL. Computed tomography (CT) demonstrated focal wall thickening of the gallbladder fundus. Drip infusion cholecystocholangiography with CT revealed no dilation, stenosis, or border irregularity of the bile duct. Results: For diagnostic and treatment purposes, cholecystectomy with wedge resection of the gallbladder bed was performed. The pathological diagnosis was IgG4-related sclerosing cholecystitis. Conclusion: It is difficult to differentiate IgG4-related sclerosing cholecystitis from gallbladder cancer in cases involving localized thickening of the gallbladder wall. In similar cases, surgical resection with cancer in mind might be performed based on present clinical knowledge.

We herein report the case of a 78-year-old woman with an intraductal tumor with scant mucin production in a moderately dilated main pancreatic duct that resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An endoscopic transpapillary forceps biopsy enabled an accurate preoperative diagnosis of the tumor as an oncocytic type intraductal papillary mucinous neoplasm (IPMN) of the pancreas microscopically showing papillary growth consisting of oncocytic cells with a typical mucin expression profile, although with few intraepithelial lumina containing mucin. This is the first case of an oncocytic type IPMN mimicking an ITPN that was able to be diagnosed preoperatively.

We present a case of acute esophageal necrosis (AEN) and two acquired esophageal stenosis cases which showed a similar clinical course after an episode of septic shock. Extensive stenosis of the distal esophagus developed in all cases, which were refractory to dilation therapy and required surgical intervention. The etiology of the latter two cases was deduced from the stenosis after septic shock-induced AEN. Since the diagnosis of AEN is based on its characteristic endoscopic findings which can only be confirmed at the onset of the disease, we therefore called these cases "septic shock-related esophageal stenosis" or abbreviated to "septic esophageal stenosis". Further study of similar cases is required for understanding the etiology and management of AEN and the relevant disorder which may cause esophageal stenosis.

Recently, the usefulness of the prone position for thoracoscopic esophagectomy has been demonstrated. Thoracoscopic resection of an esophageal submucosal tumor using a prone position also offers advantages over a lateral decubitus position. We describe 2 cases operated on using the prone position for the resection of esophageal submucosal tumor. Case 1 was a 35-year-old man, who was diagnosed with a 50×20 mm leiomyoma in the middle thoracic esophagus, and underwent right thoracoscopic tumor enucleation. Case 2 was a 61-year-old female, who had 45×30 mm esophageal schwannoma in the lower thoracic esophagus with symptoms of dysphagia, and underwent left thoracoscopic tumor enucleation. No complication was observed in both cases. Thoracoscopic esophageal submucosal resection with prone position may add the merits to conventional decubitus position, such as superior visualization, and less bleeding. The side of incision should be determined according to the location of the tumor and anatomic rationality.

Background/objectives Our institution has utilized a duodenum-preserving pancreas head resection (DPPHR) procedure for management of low-grade malignant lesions within the head of the pancreas, but this has resulted in a higher rate of postoperative complications, including pancreatic fistula and ischemic bile duct injury. To avoid these complications we recently modified DPPHR to resect all the parenchyma around the pancreatic head and to preserve the epicholedochal plexus around the bile duct. The goal of this study was to investigate outcomes with postoperative complications and disease control following this modified procedure. Methods Twenty-one consecutive patients underwent DPPHR between 1994 and 2011. Patients were retrospectively classified into one of two groups: the conventional DPPHR group (cDPPHR) or the modified DPPHR group (mDPPHR). Perioperative factors and postoperative complications were compared between these two groups. Results The median age of the 21 patients was 61 (23–77) years, and the median follow-up period was 51 months. Intra-operational blood loss was significantly smaller and duration of hospital stay was significantly shorter in the mDPPHR group than in the cDPPHR group, respectively. The rate of pancreatic fistula was markedly lower in the mDPPHR group (2/13; 15%) than in the cDPPHR group (7/8; 88%) ( P = 0.0022). For neoplastic lesions, the surgical margin was negative in all cases, and local recurrence has not occurred in either group. Conclusions For selected patients, modified DPPHR may provide clinical benefits in terms of less complications associated with shorter hospital stay.

In several clinical situations, including resection of malignant or benign biliary lesions, reconstruction of the biliary system using the Roux-en-Y jejunum limb has been adopted as the standard procedure. The basic technique and the procedural knowledge essential for most gastroenterological surgeons are described in this article, along with a video supplement. Low complication rates involving anastomotic insufficiency or stricture can be achieved by using proper surgical techniques, even following small bile duct reconstruction. Using the ropeway method to stabilize the bile duct and jejunal limb allows precise mucosa-to-mucosa anastomosis with interrupted sutures of the posterior row of the anastomosis. Placement of a transanastomotic stent tube is the second step. The final step involves suturing the anterior row of the anastomosis. In contrast to the lower extrahepatic bile duct, the wall of the hilar or intrahepatic bile duct can be recognized within the fibrous connective tissue in the Glissonean pedicle. The portal side of the duct should be selected for the posterior wall during anastomosis owing to its thickness. Meticulous inspection to avoid overlooking small bile ducts could decrease the chance of postoperative intractable bile leakage. In reconstruction of small or fragile branches, a transanastomotic stent tube could work as an anchor for the anastomosis. Electronic supplementary material The online version of this article (doi:10.1007/s00534-011-0475-5) contains supplementary material, which is available to authorized users.

Extensive intraepithelial spread of bile duct carcinoma is a common feature, seen in approximately 18% of all cases. However, this spread is rarely accompanied by bile duct strictures. We herein describe three cases of bile duct carcinoma with multiple bile duct strictures due to extensive intraepithelial spread. In all three cases, the spread of intraepithelial cancer extended into the epithelium of the peribiliary glands along the intrahepatic bile ducts with marked fibrosis on histopathological examination. It is speculated that peribiliary gland involvement by superficially spreading bile duct cancer and subsequent obstructive glandular inflammation with fibrosis might cause intrahepatic bile duct strictures even without interstitial cancer invasion.

To evaluate the prognostic impact of surgical intervention for initially-unresectable pancreatic ductal adenocarcinomas with long-term favorable responses to chemotherapy.Twelve patients with initially-unresectable pancreatic ductal carcinomas who underwent radical surgery after a favorable response to chemotherapy for six months or longer in principle were enrolled in this study. We retrospectively reviewed the charts of these 12 patients and performed a survival analysis.Initially, the included patients were unable to undergo resection secondary to locally-advanced disease in eight patients and metastatic disease in four patients. The length of preoperative therapy was five to 44 months (median 12). The operative procedure included resection of the area initially involved by tumor and regional major vessels. The postoperative mortality and morbidity rates were 0% for patients with locally-advanced disease and 50% in those with metastatic disease. R0 resection was achieved in nine patients (75%) and pathological CR was seen in one patient. Estimated overall five-year survival from initial therapy was 50.0%. The survival rate (0% at 5 years) of the four patients with metastatic disease as the cause of initial unresectability was significantly worse than that (100% at 5 years) of the eight patients with locally-advanced disease (P = 0.0014).Surgical intervention should be considered for patients with initially-unresectable pancreatic cancers who demonstrate long-term favorable responses to chemotherapy. R0 resection may significantly contribute to cure, especially in patients with initially locally-advanced disease. Large cohort prospective studies will be necessary to demonstrate the efficacy of this strategy.

Gallbladder cancer (GBC) often invades the hepatic hilum and even small tumors can cause obstructive jaundice. Operative intervention for GBC with obstructive jaundice is sometimes not recommended because it is associated with a poor prognosis. However, the extended procedure is recommended for patients with hilar cholangiocarcinoma (HC). We therefore compared the postoperative survival of patients with GBC invading the hepatic hilum with that with HC. Between 1998 and 2008, 27 patients with GBC invasion of the hepatic hilum (hGBC) and 124 with HC underwent surgical resection with curative intent in the Department of Surgical Oncology, Hokkaido University Graduate School of Medicine. This study included patients with GBC without peritoneal dissemination and liver or para-aortic lymph node metastasis. Extended right hemihepatectomy and extrahepatic bile duct resection comprise the treatment of choice for GBC with hilar invasion (hGBC). We aimed to achieve R0 outcomes by aggressive vascular resection and/or concomitant resection of directly invaded organs around the GBC along with extended right hemihepatectomy. We analyzed 27 patients with hGBC (age 58–83 years; median 71 years; male:female 13:14) and 124 with HC (age 45–80 years; median 69 years; male:female 94:30). The 3- and 5-year survival rates of 43 and 24% for hGBC and 58 and 38% for HC, respectively, did not differ significantly (p = 0.14). Preoperative obstructive jaundice was a complication in 22 (81%) and 95 (77%) patients with hGBC and HC, respectively. The 5-year survival rates were 40 and 36%, respectively, which did not differ significantly (p = 0.61). The 5-year survival rates after extended right hemihepatectomy to resect the tumor with curative intent were 34 and 34% for hGBC and HC, which did not differ significantly (p = 0.14). The prognosis after curative resection of GBC with hilar invasion is similar to that of HC in selected patients. Aggressive surgery for advanced GBC with hilar invasion might increase survival rates.

It is important to predict the development of clinically relevant pancreatic fistula (grade B/C) in the early period after pancreaticoduodenectomy (PD). This study has been carried out as a project study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHPBS) to evaluate the predictive factors associated with clinically relevant pancreatic fistula (grade B/C).The data of 1,239 patients from 11 medical institutions who had undergone PD between July 2005 and June 2009 were retrospectively analyzed to review patient characteristics and perioperative and postoperative parameters.A drain amylase level4,000 IU/L on postoperative day (POD) 1 was proposed as the cut-off level to predict clinical relevant pancreatic fistula by the receiver operating characteristic (ROC) curve. The sensitivity, specificity, and accuracy of this cut-off level were 62.2, 89.0, and 84.8%, respectively. A multivariate logistic regression analysis revealed that male [odds ratio (OR) 1.7, P = 0.039], intraoperative bleeding1,000 ml (OR 2.5, P = 0.001), soft pancreas (OR 2.7, P = 0.001), and drain amylase level on POD 14,000 IU/L (OR 8.6, P 0.001) were the significant predictive factors for clinical pancreatic fistula.The four predictive risk factors identified here can provide useful information useful for tailoring postoperative management of clinically relevant pancreatic fistula (grade B/C).

Background/Aims: Distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) is routinely accompanied by complete resection of the bilateral celiac ganglions and the circumferential plexus of the superior mesenteric artery. The postoperative condition including bowel movement, nutritional status, and tolerance to adjuvant chemotherapy has never been studied. Methods: 40 patients who underwent DP-CAR were enrolled in this study. Postoperative bowel function was estimated by the requirement of anti-diarrheal agents. Changes of nutritional parameters including body weight and laboratory data for 1 year after surgery were evaluated. Results: 15 (38%) patients needed no anti-diarrheal agent after a median follow-up period of 39 months. The other patients were well controlled for their bowel movement with anti-diarrheal drugs. 13 patients who received adjuvant chemotherapy tolerated it well despite hematologic toxicity in 7 patients who received gemcitabine. Postoperative body weight was significantly decreased and reached a plateau value at postoperative month 3. The values of laboratory data indicating nutritional status were significantly lower at 1 month after surgery and recovered between 3 and 12 months. Conclusion: The patients who underwent DP-CAR scarcely suffered from intractable diarrhea and could achieve a feasible nutritional status after surgery to be able to receive adjuvant chemotherapy.

Background/Purpose: Radical resection for hilar cholangiocarcinoma is still associated with significant morbidity and mortality. The aim of this study was to analyze short-term surgical outcomes and to validate our strategies, including preoperative management and selection of operative procedure. Methods: We surgically treated 146 consecutive patients with hilar cholangiocarcinoma with a management strategy consisting of preoperative biliary drainage, portal vein embolization, and selection of operative procedure based on tumor extension and hepatic reserve. Major hepatectomy was conducted in 126 patients, and caudate lobectomy or hilar bile duct resection in 20 patients. Results: The overall 5-year survival rate was 35.5%, with overall in-hospital mortality and morbidity rates of 3.4% and 44%, respectively. Hyperbilirubinemia (total bilirubin > 5 mg/dL, persisted for > 7 postoperative days) and liver abscess were the most frequent complications. Five among 9 patients with liver failure (total bilirubin > 10 mg/dL) encountered in-hospital mortality. Four out of 5 mortality patients had suffered circulatory impairment of the remnant liver due to other complications. Multivariate analysis revealed that operative time is a single independent significant predictive factor (odds ratio, 1.005; 95% confidence interval, 1.000-1.010, P = 0.04) for postoperative complications. Conclusions: Aggressive resection for hilar cholangiocarcinoma, performed in accordance with strict management strategy, achieved acceptable low mortality. Prolonged operative time was a risk for morbidity following hepatobiliary resection.

Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is a common entity. In colorectal liver metastasis, microscopic tumor invasion into the intrahepatic portal vein is also usually observed, but the incidence of macroscopic tumor thrombus in the first branch and trunk of the portal vein is rare. Most reported cases of PVTT from colorectal cancer had concomitant metastatic nodules in liver parenchyma, and the PVTT was continuous with the liver nodule, like PVTT in HCC. We present a case of PVTT from colorectal cancer with no definite metastatic nodules in liver parenchyma. A 58-year old man underwent laparoscopic high anterior resection for rectosigmoid carcinoma accompanied by bulky tumor thrombus in the branch of the inferior mesenteric vein. Six months later, he received left lobectomy and left caudate resection for liver metastasis. The resected specimen demonstrated there was no metastatic nodule in liver parenchyma and that the left portal system was filled with the tumor thrombus. The patient is alive with no sign of recurrence 66 months after hepatectomy. Even if there is a macroscopic PVTT from colorectal cancer, a better prognosis may be expected when the tumor can be completely resected en-bloc by anatomic hepatectomy including PVTT.

3回の開腹歴がある79歳の女性が, イレウスの診断で当院内科に入院となった. 同日イレウス管の挿入が行われたが, 十二指腸水平脚近位にとどまり, より遠位に進めることが困難であった. 翌々日, 症状の改善なく, イレウス管造影検査で腸管外への造影剤の漏出と, 腹部CTで十二指腸周囲のfree airを認めたため, イレウス管による十二指腸穿孔の診断で緊急開腹術を施行した. 手術所見では十二指腸水平脚に憩室が存在し, 同部よりイレウス管の脱出を認めた.憩室切除, ドレナージ術, 結腸右半切除術を施行した. 十二指腸憩室が穿孔を来すことはまれであり, 穿孔例の多くは下行脚の憩室である. 医原性穿孔は3例のみ報告されているが, イレウス管による穿孔例は, 本邦では他に報告は見当たらない. イレウス管挿入時に十二指腸にて先進しない場合は, 憩室の存在も念頭におき, 慎重な操作を心がける必要があると考えられた.

大網裂孔ヘルニアはまれな疾患であり, 特徴的な臨床所見に乏しく術前診断は困難といわれる. 診断の遅れから開腹時すでに腸壊死を来し腸切除を必要とすることも多い. 今回, 我々は大網裂孔ヘルニアの診断と治療に腹腔鏡が有用であった1例を経験したので報告する. 症例は16歳の女性で, 開腹歴はない. 腹痛を主訴に救急外来を受診し, 臍周囲に強い圧痛を認めた.腹部CTでは特記すべき異常所見を認めなかった. 原因不明の急性腹症と診断され当科入院となった. 4時間後, 疼痛が増強し腸液混じりの嘔吐が出現したため, 内ヘルニア嵌頓を疑い緊急手術を施行した. 腹腔鏡検査を施行し, 大網に生じた異常裂孔に小腸が嵌頓しているのが発見された. 大網を切離し裂孔を開放した. 小腸に壊死所見を認めなかったため, 腸切除は施行しなかった. 術後3日目に退院した. 我々が検索しえた範囲では, 腹腔鏡下で診断し整復しえた大網裂孔ヘルニア症例は本症例が本邦初の報告である.

With the improvement of perioperative management and surgical techniques as well as the accumulation of knowledge on the oncobiological behavior of bile duct carcinoma, the long-term prognosis of hilar cholangiocarcinoma has been improving. In this article, the authors review the recent developments in surgical strategies for hilar cholangiocarcinoma, focusing on diagnosis for characteristic disease extension, perioperative management to reduce postoperative morbidity and mortality, surgical techniques for extended curative resection and postoperative adjuvant therapy.

This report describes a case of a patient with a large solid gallbladder adenocarcinoma that was completely resected through aggressive surgery. The patient was a 57-year-old woman who had been diagnosed with advanced gallbladder cancer, had no indications for surgical resection and was scheduled to undergo systemic chemotherapy. She presented to our hospital for a second opinion. At the time of assessment, her tumor was large but was well-localized and had not invaded into the surrounding tissues, indicating that surgical resection was a reasonable option. Subsequently, the tumor was completely extracted via right hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Histopathologically, the tumor was a solid adenocarcinoma. Although there are relatively few reports in the literature regarding solid gallbladder adenocarcinoma, well-localized growth appears to be a characteristic feature. On the basis of a tumor’s progression behavior, aggressive surgical treatment might be indicated even when the tumor has grown to a considerable size.

Due to advances in endoscopic equipment and techniques, preoperative endoscopic biliary drainage (EBD) has been developed to serve as an alternative to percutaneous transhepatic biliary drainage (PTBD). This study sought to clarify the benefit of EBD in comparison to PTBD in patients who underwent radical resections of hilar cholangiocarcinoma. One hundred and forty-one patients underwent radical surgery for hilar cholangiocarcinoma between 2000 and 2008 were retrospectively divided into two groups based on the type of preoperative biliary drainage, PTBD (n = 67) or EBD (n = 74). We investigated if the different biliary drainage methods affected postoperative survival and mode of recurrence after median observation period of 82 months. The survival rate for patients who underwent EBD was significantly higher than those who had PTBD (P = 0.004). Multivariate analysis revealed that PTBD was one of the independent factors predictive of poor survival (hazard ratio: 2.075, P = 0.003). Patients with PTBD more frequently developed peritoneal seeding in comparison to those who underwent EBD (P = 0.0003). PTBD was the only independent factor predictive of peritoneal seeding. In conclusion, EBD might confer an improved prognosis over PTBD due to prevention of peritoneal seeding, and is recommended as the initial procedure for preoperative biliary drainage in patients with hilar cholangiocarcinoma.

We experienced a case of malignant stromal tumor of the ileum. A 59-yer-old women complaining of abdominal pain, abdominal fullness and vomiting was referred to the hospital with a diagnosis of intestinal obstruction. She was treated by a long tube to release the obstruction. Thereafter, upper gastrointestinal series, ultasonography, CT, magnetic resonance imaging, and angiography revealed a tumor which was 11cm in diameter, well-delineated and hypervascular, and developed extramurally at the ileum. Under the diagnosis of leiomyosarcoma, a partial resection of the ileum including the tumor was performed. Histologically, the tumor was mainly composed of proliferated spindle cells and partially epithelioid cells which have mitotic figure 6/10 high power field. Immunohistologically, the tumor was not stained for α-smoogh muscle actin, desmin and S-100 protein, but for NSE and CD34. Though the tumor was positive for NSE, the differentiation to the nerve was not found. Therefore, it was diagnosed as uncommitted type of malignant gastrointestinal stromal tumor (GIST) of the ileum. GIST is a relatively new concept, and hence, further studies on the prognosis, mode of recurrence, frequency, and differences in imaging methods according to sub-classification of GIST would be needed.

There have been few papers on how to treat hepatobiliary malignancies after ERCP-related pancreatitis focusing on the timing of the operation and postoperative complications. The aim of this study was to clarify the relationship among the time after the pancreatitis, the complexity of the operation, and the characteristic postoperative complications.The clinicopathological characteristics of five patients with hepatobiliary malignancies who had a prior history of ERCP-related pancreatitis were analyzed.The five patients included two with extrahepatic bile duct carcinomas, two with ampulla of Vater carcinomas, and one with intrahepatic hilar cholangiocarcinoma. The median time to the operation from pancreatitis was 31 (16-116) days. The median operation time and blood loss were 661 (576-924) min and 3695 (2730-7240) mL, respectively. Various postoperative complications were seen in all cases including acute respiratory distress syndrome and infection of peripancreatic necrosis. The postoperative mortality rate was 0%, with a morbidity rate of 100%. R0 operations were performed in all five cases.Surgery for hepatobiliary malignancies after ERCP-related pancreatitis appears to have a high morbidity rate. The surgery must strike a balance between curability of the malignancy and safety with respect to the frequent postoperative complications.

ObjectivesTo assess the safety and feasibility and discuss the oncological impact of a portal vein resection using the no-touch technique with a hepatectomy for locally advanced hilar cholangiocarcinoma.Patients and MethodsFrom 2005 to March 2009, 49 patients with hilar cholangiocarcinoma underwent a major right-sided hepatectomy with curative intent. Portal vein resection was performed using the no-touch technique in 36 patients (PVR group) but the portal vein was not resected in the other 13 patients (NR group). Peri-operative data and histological findings were compared between the two groups. Moreover, tumour recurrence and survival rates after surgery were calculated and compared for each group.ResultsAlthough the tumours of the patients in the PVR group were more locally advanced, the residual tumour status and tumour recurrence rate were similar and there was no significant difference in long-term survival between the two groups: 5-year survival rates in the PVR and NR groups were 59% and 51%, respectively (P = 0.353). In-hospital mortality was encountered in 2 of the 49 patients.ConclusionA portal vein resection using the no-touch technique with a right-sided hepatectomy had a positive impact on survival and is feasible in terms of long-term outcomes with acceptable mortality.

Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) provides good local control for locally advanced pancreatic body cancer, but early recurrence still occurs. In this study, we aimed to establish a new scoring system to predict prognosis using preoperative factors in patients with locally advanced pancreatic body cancer who undergo DP-CAR.Prognostic factors were analyzed using various data collected retrospectively from 50 consecutive patients who underwent DP-CAR. Using these preoperative factors, a scoring system to predict prognosis was established.Multivariate analysis identified intraoperative blood loss (≥940 mL; hazard ratio [HR], 25.179; P = .0003), preoperative platelet counts (150 × 10(9)/L; HR, 7.433; P = .0043), preoperative C-reactive protein (CRP) levels (≥0.4 mg/dL; HR, 7.064; P = .0018), and preoperative carbohydrate antigen 19-9 (CA19-9) levels (≥300 U/mL; HR, 8.197; P = .0053) as independent adverse prognostic factors. For the 3 preoperative factors, preoperative platelet counts150 × 10(9)/L, preoperative CRP levels ≥0.4 mg/dL, and preoperative CA19-9 levels ≥300 U/mL were allocated 1 point each. The total score was defined as the Preoperative Prognostic Score (PPS). The estimated disease-specific 1- and 5-year survival rates for the 26 patients with PPS0 were 95.7%, and 49.1%, respectively, and for the 15 patients with PPS1, they were 86.7% and not available, respectively. The median survival times for PPS0 and PPS1 were 50.6 and 22.3 months, respectively. In contrast, in the 9 patients with PPS2/3, 1- and 5-year survival rates were 33.3% and 0%, respectively, and median survival time was only 7.7 months.A new prognostic scoring system using the preoperative platelet count, CRP, and CA19-9 enables preoperative prediction of prognosis and facilitates selection of appropriate treatment for borderline resectable cases of locally advanced pancreatic body cancer.

Pancreatic cancer is an aggressive cancer with poor prognosis. Little is known about the immune response in the tumor microenvironment after chemotherapy for initially unresectable tumor. The purpose of this study was to investigate the immunological effects of chemoradiation therapy in the tumor microenvironment of pancreatic adenocarcinoma. Seventeen patients with pancreatic adenocarcinoma with and without preoperative chemoradiation therapy were retrospectively analyzed using immunohistochemical methods for HLA class I heavy chain, CD4(+), CD8(+), CD45RO (+) and Foxp3(+) T cell infiltrations. Seven of the 17 study patients received preoperative chemoradiation therapy. There were no statistically significant differences in the number of CD4(+) and CD8(+) T cell infiltrations in the tumor microenvironment. However, the number of Foxp3(+) T cell infiltrations was significantly lower in the neoadjuvant chemoradiation therapy group. The HLA class I expression status was the same between the two groups. In conclusion, preoperative chemoradiation therapy in pancreatic adenocarcinoma is useful for reducing regulatory T cell levels in combination with its direct cytotoxic effects.

Background/aims Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms. Little is known about the mode of recurrence and long term prognosis after resection. We aimed to evaluate the surgical indication, especially for the patients with concomitant multiple liver metastases or extreme local invasions. Methodology The overall survival (OS) and the disease free survival (DFS) were statistically analyzed for twenty one patients with PNETs who underwent surgical intervention in our institute. The patients were divided into 2 groups, G1 NET (grade 1 neuroendocrine tumor: n=11) and G2 NET (grade 2 neuroendocrine tumor: n=10), according to WHO 2010 classification. The radical operation was indicated if curative resection were expected to be achievable. Otherwise,alternative multi-disciplinary treatments were introduced especially for the hepatic metastasis or repeated recurrences. Results Median follow-up period was 37 months (range 7-69). OS was 100% at 3 years and 86% at 5 years. DFS was 62% at 3 years and 39% at 5 years. Disease recurrence developed more frequently in G2 NET, compared to G1 NET. However, there was statistically no difference for the OS between these two groups. Conclusions Appropriate radical operation with multi-disciplinary treatments could contribute to the patients' survival in the treatment strategy of PNETs.

We have already reported the feasibility, safety, and excellent long-term results of distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) for locally advanced pancreatic body cancer. An international standard for the surgical technique of DP-CAR has yet to be established.DP-CAR was carefully performed in 42 patients in Hokkaido University Hospital from 1998 to July 2007. Arterial blood flow alteration and collateral flow development toward the liver and stomach was obtained following preoperative routine transcatheter arterial embolization of the common hepatic artery. The right-sided approach to the superior mesenteric artery and celiac artery, and the preservation of the inferior pancreatoduodenal artery during the dissection of the plexus around the pancreatic head, are the key techniques in DP-CAR.The operative morbidity and mortality were 43 and 4.8%, respectively. R0 resection could be done in 39 (93%) patients. Median operation time and intraoperative blood loss were 478 min and 1030 ml, respectively. Ischemic gastropathy was complicated in 5 (12%) patients, but liver abscess was found in only one patient and no liver failure was encountered.We emphasize again the feasibility and safety of DP-CAR; it should be a treatment of choice for locally advanced pancreatic body cancer.

BACKGROUND/AIMS: Little information is available about the long-term prognosis after hepatectomy for liver metastases of neuroendocrine tumors (NETs). To clarify the prognosis for liver metastases of NETs after hepatectomy and to identify a practical and useful surgical indication for hepatic metastases of NETs. METHODOLOGY: Twenty-four patients with NET were divided into 2 groups: the nHM group (patients without hepatic metastasis, n=13) and the HM group (patients with hepatic metastasis or recurrences, n=11). Hepatectomy was indicated for metastases or disease recurrences in the liver if R0 resection was expected to be achievable. Patient clinicopathological features, mode of recurrences and treatment for them were evaluated retrospectively. RESULTS: The median follow-up period for the 24 patients was 34 months (range 7-69) and the disease specific survival rate was 82% at 5 years. DSS at 5 years did not differ between patients with and without hepatic recurrence (91% vs. 75% respectively, p=0.6144), even though the histological grade and the MIB-1 index were higher in the HM group. CONCLUSIONS: Patient prognosis was acceptable following our policy of hepatectomy for NET liver metastases. Survival could be improved by intensive multimodal treatment.

Pancreatic endocrine tumors (PETs) are relatively rare. Owing to their slow growing characteristics, an aggressive surgical approach has been considered to improve patients' survival. A case of PET with portal vein (PV) thrombus, successfully treated by distal pancreatectomy with concomitant PV resection and removal of PV tumor thrombus, preserving collateral pathways, is reported.

The controversy over whether and how to perform preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCA) remains unsettled. Arguments against PBD before pancreatoduodenectomy have recently been gaining momentum. However, the complication-related mortality rate is as high as 10% for patients with HCA who have undergone major liver resection, and liver failure is a major cause of postoperative death. This suggests the need for PBD to treat jaundice in HCA patients scheduled for major surgical resection of the liver and that major surgery should be performed only after the recovery of hepatic function. No definite criteria or guidelines outlining indications for PBD are currently available. In patients with HCA, PBD may be performed by either percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD). No consensus, however, has been reached regarding which drainage method is more appropriate. No reported study has compared the effectiveness of PTBD, endoscopic biliary stenting (EBS), and endoscopic nasobiliary drainage (ENBD) in patients with HCA. This review summarizes the results of our study comparing the three methods and outlines the preoperative endoscopic management of segmental cholangitis (SC) in HCA patients undergoing PBD.

Several reports have noted epidemiological differences in the prevalence or prognostic significance of p53 mutants with arginine (R) or proline (P) at the codon 72 polymorphism (R72/P72) in certain cancer types, but the biological significance of these variants is unclear. The ability of p53 mutants to interact with and inactivate the p53 homolog p73 was recently reported to depend on the conformational state of the p53 protein and the residue at codon 72. Since the conformation of p53 mutants may influence their ability to transdominantly inhibit wild-type p53, we tested whether there was a correlation between the amino acid at codon 72 and the transdominance of p53 alleles found in tumors. The transdominance test was performed using a simple yeast transcription assay, and the amino acid at codon 72 was determined by sequencing. A total of 100 p53 mutants were tested. Compared with the germline frequency (R:P = 427:297), an extreme bias in favor of the R72 allele was observed with recessive mutants (R:P = 50:7, P < 0.0002), whereas no selection for the R72 allele was seen with transdominant mutants (R:P = 23:20). p53 and p73 are known to transactivate overlapping sets of target genes. We interpret the R72 bias with recessive mutants as evidence that decreased activation of p53 target genes provides a selective growth advantage to tumor cells during the stage of tumorigenesis in which a wild-type and mutant p53 allele coexist. We suggest that transdominant p53 mutants achieve this by inactivation of the remaining wild-type p53 allele, whereas recessive p53 mutants achieve it through inactivation of p73.

What impact does pancreaticoduodenectomy (PD) have on exocrine function? Does the pancreatic anastomosis remain patent? When stool elastase became available for testing in November 2001, we began preoperative assessment and then increasingly employed postoperative measurements. From December 2001 until March 2006, 182 patients underwent PD by the same surgeon. Preoperative stool elastase was measured in 138 (76%) patients and was repeated postoperatively at 3 +/- 1 month, 12 +/- 2 months, and 24 +/- 3 months. At the same time periods, an abdominal CT scan was used to assess patency of the pancreatic anastomosis as implied by pancreatic duct dilation in the remnant (dilation = duct3 mm or, if duct dilated preoperatively, then duct that failed to decrease in size). All cases were reconstructed with duct-to-mucosa pancreaticojejunostomy. Stool elastase was expressed as normal (200 microg/gram stool), moderately reduced (100-200 microg/gram), or severely reduced (100 microg/gram). Preoperative stool elastase values were "normal" in 78% (pancreatic cancer 32% normal vs. all other groups78%; Por = 0.001). As compared with preoperative values, the percent of cases with reduced elastase levels at 3 months, 1 year, and 2 years postoperatively was 48%, 73%, and 50%, respectively. The CT scans at the time of the 69 stool elastase measurements after PD showed pancreatic duct dilation in the pancreatic remnant in 9 of 69 (9%) stools but was not more frequent in the group with decreased elastase. Based on cases elastase, one third of patients about to have PD will have exocrine insufficiency, an observation most common among the patients with pancreatic cancer (68%). Stool elastase levels are further depressed in the majority of cases after PD from parenchymal loss because we could not implicate an occluded pancreatic anastomosis. These results suggest that, after PD, exocrine supplementation should be given to all patients with pancreatic cancer, especially those with impending adjuvant therapy. To further improve the long-term results after PD, each surgeon should assess the effect of their own type of pancreaticoenteric technique on exocrine function.

Activated Akt/protein kinase B transmits oncogenic signals leading to inhibition of apoptosis, cellular proliferation, and tolerance to hypoxia. Presently, mutational inactivation of PTEN and activation of Ras are considered to be the major causes of Akt activation. Here we report differential mechanisms of constitutive Akt activation in 4 human pancreatic cancer cell lines (KMP-3, KMP-4, PCI-66, and PCI-68). These 4 cell lines displayed phosphorylation and functional activation of Akt both in the presence and absence of serum, while three control cell lines (PCI-79, KMP-8, and PSN-1) did so only in the presence of serum in culture. All the 7 cell lines harbored K-Ras activated by mutations at codon 12 resulting in MAP kinase kinase (MEK1/2) phosphorylation, and all except one (KMP-8) had p53 mutations, indicating that these mutations are not sufficient for constitutive Akt activation. KMP-3 and KMP-4 had lost PTEN function owing to loss of expression or a mutation, but PCI-66 and PCI-68 retained wild-type PTEN. Phosphorylation of Akt was inhibited by the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and the tyrosine kinase inhibitor genistein in KMP-3 and KMP-4 cells, indicating that upstream signals are required for Akt activation in these two cell lines. In contrast, neither LY294002 nor genistein inhibited Akt activation in PCI-66 and PCI-68 cells, indicating the involvement of another unknown mechanism of Akt activation independent of PI3K-mediated signaling to Akt. Irrespective of the differential mechanisms, the 4 cell lines showed similar mRNA expression patterns of 49 genes assessed by cDNA array as compared to the 3 cell lines without Akt activation, suggesting that the mechanisms have the same consequences on the downstream signaling of the constitutive Akt activation.

In lung cancer patients, hypercalcemia is a fairly common metabolic problem associated with malignancy. However, the occurrence of hypercalcemia in lung cancer patients means an ominous prognostic sign. As hypercalcemia often causes early death, quick diagnosis and treatment for hypercalcemia are required. A 69-year-old woman was admitted to our hospital with anorexia caused by hypercalcemia. On admission, serum level of PTH was elevated and PTHrP was normal. From the results of CT findings and transbronchial lung biopsy, the cause of the hypercalcemia was determined as lung cancer incidentally complicated with primary hyperparathyroidism. First, serum calcium level was returned to normal through hydration with saline and bisphosphonates. Next, left hemithyroidectomy for primary hyperparathyroidism was performed. Histologically, the tumor was diagnosed as parathyroid adenoma. Fifteen days later, left lower lobectomy for primary lung cancer was performed under a video-assisted thoracoscopic approach. Histologically, the tumor was diagnosed as a moderately differentiated adenocarcinoma. Four years and three months after the operation, the patient is alive and well with no sign of recurrence. When a lung cancer patient is complicated with hypercalcemia, we need to consider that primary hyperparathyroidism is a possible cause of the hypercalcemia.