Joe Matsumoto

Oncological benefit of preoperative endoscopic biliary drainage in patients with hilar cholangiocarcinoma

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.

Preoperative biliary drainage for hilar cholangiocarcinoma: which stent should be selected?

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.

A new preoperative prognostic scoring system to predict prognosis in patients with locally advanced pancreatic body cancer who undergo distal pancreatectomy with en bloc celiac axis resection: A retrospective cohort study

BACKGROUND 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. METHODS 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. RESULTS 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 counts <150 × 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. CONCLUSION 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.

Portal vein resection using the no-touch technique with a hepatectomy for hilar cholangiocarcinoma

OBJECTIVES To 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 METHODS From 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. RESULTS Although 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. CONCLUSION A 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.

Differential Mechanisms of Constitutive Akt/PKB Activation and Its Influence on Gene Expression in Pancreatic Cancer Cells

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.

Postoperative Bowel Function and Nutritional Status following Distal Pancreatectomy with En-Bloc Celiac Axis Resection

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.

Techniques of biliary reconstruction following bile duct resection (with video)

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.

Novel aspects of preoperative chemoradiation therapy improving anti-tumor immunity in pancreatic 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.

Portal vein tumor thrombus from colorectal cancer with no definite metastatic nodules in liver parenchyma

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.

Thoracoscopic enucleation of esophageal submucosal tumor by prone position under artificial pneumothorax by CO2 insufflation.

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.