A novel reaction force-fluorescence measurement system for evaluating pancreatic juice leakage from an excised swine pancreas during distal pancreatectomy.

BACKGROUND: Resection using a stapler is a popular approach to distal pancreatectomy. However, the resulting leakage of pancreatic juice represents a serious problem. We have developed a force-fluorescence measurement as a first step towards the quantitative evaluation of pancreatic leakage due to tissue tearing under compression. METHODS: The system comprises a testing machine with an indenter, similar in size to a stapler, which controls compression speed and measures reaction force, and a fluorescence measurement system to measure pancreatic juice leakage. Pancreatic juice leakage is measured as the maximum value of the increasing rate of fluorescence intensity (max value). Ten excised swine pancreases were compressed at a speed of 500, 100, and 10 mm/min until their thicknesses became 2 mm. RESULTS: A strong positive correlation (0.804) was observed between the increase in max value before and after compression and the amount of reaction force drop due to tissue destruction. No pancreatic juice leakage was observed when compressed slowly (10 mm/min). CONCLUSIONS: We have successfully developed a novel force-fluorescence measurement system that can detect and quantify pancreatic juice leakage caused by tissue tearing. This system can determine the optimal compression conditions for preventing pancreatic juice leakage.

Diffusion-weighted MR imaging of pancreatic cancer and inflammation: Prognostic significance of pancreatic inflammation in pancreatic cancer patients.

BACKGROUND: Pancreatic cancer often accompanies chronic obstructive pancreatitis (COP) due to obstruction of the main pancreatic duct, and the inflammatory environment may enhance cancer progression. The purpose of this study is to evaluate COP using the apparent diffusion coefficient (ADC) value measured by diffusion-weighted MR imaging (DWI), and to assess its prognostic significance in pancreatic cancer. METHODS: Twenty-eight patients (16 men, 12 women; mean age 67.1 years) with pancreatic cancers who underwent DWI followed by curative surgery were evaluated. The ADC value of pancreatic parenchyma upstream to the tumor (upstream pancreas) was measured and compared with the upstream pancreatic duct dilatation to assess whether DWI could reflect COP. The ADC values of tumor and upstream portion were compared with overall survival (OS) using Cox regression and Kaplan-Meier analysis. RESULTS: The ADC value of upstream pancreas was significantly lower in patients with greater dilated pancreatic duct than those with less (P = 0.03). In univariate Cox regression analysis, the ADC value of upstream pancreas showed a significant association with OS (P = 0.01), but that of tumor did not (P = 0.06). In Kaplan-Meier analysis, patients with lower ADC value of upstream pancreas (<1.36 × 10(-3) mm(2)/s) were significantly associated with poor OS (P = 0.0006). In multivariate analysis, the ADC value of upstream pancreas was identified as an independent prognostic factor (P = 0.01; hazards ratio, 0.05; 95% CI, 0.004-0.59). CONCLUSIONS: The ADC value of upstream pancreas was an independent prognostic factor for OS in pancreatic cancer patients. Inflammatory environment may play an important role in pancreatic cancer progression.

Feasibility and efficacy of gemcitabine plus cisplatin combination therapy after curative resection for biliary tract cancer.

BACKGROUND: The aim of this multi-institutional study was to assess the feasibility and the efficacy of gemcitabine plus cisplatin (CDDP) combination therapy (GC therapy) for biliary tract cancer (BTC) in the adjuvant setting. METHODS: Eligible patients identified between January 2008 and January 2013 were enrolled. GC therapy at 1,000 mg/m(2) of gemcitabine and 25 mg/m(2) of CDDP on days 1 and 8 repeated every 3 weeks was performed for 6 months. The primary endpoint was the feasibility and the adverse events, and the secondary endpoint was recurrence-free survival (RFS) and overall survival (OS). RESULTS: Among 29 evaluable patients, the protocol was completed in 21 (72%) patients. Relative dose intensity (RDI) of gemcitabine and CDDP was 77% and 81%, respectively. There was no difference in the completion rate and the RDI between patients who underwent resection with vs. without major hepatectomy. Grade 3-4 toxicities included leukopenia (14%) and neutropenia (27%). Two-year RFS and 2-year OS was 59% and 90%, respectively. CONCLUSIONS: Standard dose of GC therapy is tolerable in patients with BTC who underwent curative resection either with or without major hepatectomy. The survival effect of this regimen is promising, but further comparative study is needed.

Focal segmental glomerular sclerosis recurrence with massive proteinuria and anuria immediately after kidney transplantation.

Here, we report a case of focal segmental glomerular sclerosis (FSGS) recurrence immediately (47 minutes) after transplantation. A 1-hour biopsy specimen showed large periodic acid-Schiff-positive granules within the cells of the swollen proximal tubule, while electron microscopy revealed podocyte swelling and partial foot process effacement. These findings were worse on day 2 biopsy. Massive proteinuria and anuria were then observed. Two courses (2 × 2 times) of plasmapheresis and rituximab were administered, and the graft function gradually recovered. A day 22 biopsy specimen showed improvement in findings compared to those observed on day 2. One year after transplantation, no signs of FSGS recurrence are evident, and graft function remains good.

Correlation of apparent diffusion coefficient measured by diffusion-weighted MRI and clinicopathologic features in pancreatic cancer patients.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) in patients with pancreatic cancer by comparing the apparent diffusion coefficient (ADC) value with clinicopathologic features. METHODS: Twenty-two consecutive patients (12 men, 10 women; mean age 64.4 years) with pancreatic cancer underwent DWI before surgery. We retrospectively investigated the correlations between tumor ADC value and clinicopathologic features. RESULTS: Apparent diffusion coefficient value was significantly lower for pancreatic cancer than for noncancerous tissue (P < 0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.21 × 10(-3) mm(2)/s to distinguish pancreatic cancer from noncancerous tissue. There was a significant negative correlation between ADC value and tumor size (r = -0.59, P = 0.004) and between ADC value and number of metastatic lymph nodes (r = -0.56, P = 0.007). Tumors with low ADC value had a significant tendency to show high portal venous system invasion (P = 0.02) and extrapancreatic nerve plexus invasion (P = 0.01). CONCLUSIONS: Apparent diffusion coefficient value appears to be a promising parameter for detecting pancreatic cancer and evaluating the degree of malignancy of pancreatic cancer.

A Review of Autologous Islet Transplantation.

Autologous islet transplantation after total or semitotal pancreatectomy aims to preserve insulin secretory function and prevent the onset of diabetes. The major indication for pancreatectomy is chronic pancreatitis with severe abdominal pain, a benign pancreatic tumor, and trauma. The metabolic outcome of autologous islet transplantation is better than that of allogeneic transplantation and depends on the number of transplanted islets. Achieving islet isolation from a fibrous or damaged pancreas is one of the biggest challenges of autologous islet transplantation; a major complication is portal vein thrombosis after crude islet infusion. However, the incidence of portal vein thrombosis has decreased as islet preparation techniques have improved over time.

Use of omentum or falciform ligament does not decrease complications after pancreaticoduodenectomy: nationwide survey of the Japanese Society of Pancreatic Surgery.

BACKGROUND: Wrapping is thought to prevent pancreatic fistula and postoperative hemorrhage for pancreaticoduodenectomy (PD), and we analyzed whether omentum/falciform ligament wrapping decreases postoperative complications after PD. METHODS: This is a retrospective study of wrapping using the omentum/falciform ligament in patients that underwent PD between January 2006 and June 2008 in 139 institutions that were members of the Japanese Society of Pancreatic Surgery. RESULTS: Ninety-one institutions responded to the questionnaires, and data were accumulated from 3,288 patients. The data from 2,597 patients were acceptable for analysis; 918 (35.3%) patients underwent wrapping and 1,679 patients did not. A pancreatic fistula occurred in 623 patients (37.3%) in the nonwrapping group, in comparison to 393 patients (42.8%) in the wrapping group (P = .006). The incidence of a grade B/C pancreatic fistula was lower in the nonwrapping group than the wrapping group (16.7% vs. 21.5%; P = .002). An intra-abdominal hemorrhage occurred in 54 patients (3.2%) in the nonwrapping group, which was similar to the incidence in the wrapping group (32 patients; 3.5%). The mortality was 1.3% and 1.0% in nonwrapping and wrapping groups, respectively. A multivariate analysis revealed 7 independent risk factors for pancreatic fistula; male, hypoalbuminemia, soft pancreas, long operation time, extended resection, pylorus preservation, and omentum wrapping. There were 4 independent risk factors for early intra-abdominal hemorrhage and 2 independent risk factors for late intra-abdominal hemorrhage. CONCLUSION: This retrospective study revealed that omentum wrapping did not decrease the incidence of pancreatic fistula. An additional validation study is necessary to evaluate the efficacy of wrapping for PD.

Morphometric and immunohistochemical study of cholangiolocellular carcinoma: comparison with non-neoplastic cholangiole, interlobular duct and septal duct.

BACKGROUND/PURPOSE: The origin of cholangiolocellular carcinoma (CoCC) is still controversial. To solve this problem, morphometric and immunohistochemical features of CoCC were examined. MATERIALS AND METHODS: Cancerous ducts: 15 CoCC lesions from 13 resected and two autopsied cases. Non-neoplastic ducts: 20 specimens of non-cancerous areas of eight resected CoCC cases and of 12 resected hepatocellular carcinoma (HCC) cases. From these specimens, cholangioles, interlobular ducts of small size (ILD-S), interlobular ducts of medium size (ILD-M) and septal ducts were randomly selected. MORPHOMETRY: The outer and inner diameters of these ducts were measured. Immunohistochemistry: two hepatocyte markers [Hep Par 1 and α-fetoptotein (AFP)], two cholangiocyte markers (cytokeratin CK7, CK19), a marker for mucin (Muc1), a hepatic stem/progenitor cell marker (c-Kit) and epithelial membrane antigen (EMA) were used. RESULTS: Morphometry: both mean values of the outer and inner diameters of CoCC were far larger than those of cholangioles, and showed intermediate values between those of ILD-S and ILD-M. Immunohistochemistry: all ducts of CoCCs were negative for the two hepatocyte markers and positive for CK 7. Most CoCC ducts were positive for CK 19. Positive rate of c-Kit of cholangiole was most remote from that of CoCC. The positive rates of EMA in the membranous area of ducts were similarly very high in CoCC, cholangiole and ILD-S. CONCLUSION: These results suggest that CoCCs may originate from ILDs.

Survival predictors of patients with primary duodenal adenocarcinoma.

This single-institution experience retrospectively reviewed the outcomes in 21 patients with primary duodenal adenocarcinoma. Twelve patients underwent curative surgery, and 9 patients underwent palliative surgery at the Chiba University Hospital. The maximum follow-up period was 8650 days. All pathologic specimens from endoscopic biopsy and surgical specimens were reviewed and categorized. Twelve (57.1%) patients underwent curative surgery (R0): 4 pancreaticoduodenectomies (PD), 4 pylorus-preserving PDs (PpPD), 2 local resections of the duodenum and 2 endoscopic mucosal resections (EMR). Palliative surgery was performed for 9 patients (42.9%) following gastro-intestinal bypass. The median cause-specific survival times were 1784 days (range 160-8650 days) in the curative surgery group and 261 days (range 27-857 days) in the palliative surgery group (P = 0.0003, log-rank test). The resectability of primary duodenal adenocarcinoma was associated with a smaller tumor size, a lower degree of tumor depth invasiveness, and less spread to the lymph nodes and distant organs.

Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma.

BACKGROUND/PURPOSE: Hepatocellular carcinomas (HCCs) commonly originate from pre-malignant lesions consisting of mature hepatocytes. However, recent studies have suggested that some HCCs emerge from hepatic stem/progenitor cells because stem/progenitor cell markers and cholangiocyte markers are found in these HCCs. At the same time, the expression of stem/progenitor cell markers and cholangiocyte markers may also indicate de-differentiation and transdifferentiation of ordinary HCC cells. This study was performed to help clarify the uncertainty surrounding these HCCs. METHODS: Sixty-eight surgically resected HCC lesions no larger than 5 cm were studied immunohistochemically using a hepatocyte marker (Hepatocyte), 2 cholangiocyte markers (cytokeratins CK7 and CK19), a marker for mucin (Muc1), and a hepatic stem/progenitor cell marker (C-kit). RESULTS: Hepatocyte, CK7, CK19, Muc1 and C-kit were positively stained in 68 cases (100%), 51 cases (75.0%), 15 cases (22.1%), 8 cases (11.8%) and 8 cases (11.8%), respectively. In those cases positive for CK7, CK19, Muc1 and C-kit, the positively stained cells formed small foci within a large area of negatively stained cells. Small-sized positive cells suggesting hepatic/stem cell origin were found rarely. CONCLUSIONS: The positivity of cholangiocyte markers, the stem/progenitor cell marker and mucin production were thought to be due to transdifferentiation of HCC cells rather than malignant transformation of stem/progenitor cells.

Arterio-biliary fistula as rare complication of chemoradiation therapy for intrahepatic cholangiocarcinoma.

Significant hemobilia due to arterio-biliary fistula is a very rare complication of chemoradiation therapy (CRT) for unresectable intrahepatic cholangiocarcinoma (ICC). Here we report a case of arterio-biliary fistula after CRT for unresectable ICC demonstrated by angiographic examinations. This fistula was successfully treated by endovascular embolization. Hemobilia is a rare complication, but arterio-biliary fistula should be considered after CRT of ICC.

Carcinosarcoma of the liver.

Herein we present a 73-year-old man with primary carcinosarcoma of the liver, a rare malignant tumor of the liver. The case was followed up due to HBV-related liver cirrhosis. Regular check-up by ultrasound demonstrated a hyperechoic tumor in the left lobe of the liver, and he was referred and admitted to our hospital. Dynamic CT studies revealed a mostly hypoenhancing hepatic mass with a peripheral ring enhancement. Surgical resection was performed, and the resected tumor was macroscopically a simple nodular type, 3 cm in diameter, with a dense fibrous capsule. Microscopically, undifferentiated cells were dominant in the tumor, while moderately differentiated hepatocellular carcinoma (HCC) were also observed. A transitional zone was noted between the undifferentiated tumor and HCC. Tumor tissue with adenocarcinoma, osteosarcoma and chondrosarcoma were also detected. Immunohistochemical studies demonstrated that tumor cells were HepPar 1 positive in hepatocellular carcinoma, and CK19 and partly CK7 positive in adenocarcinoma. Moreover, CD56, chromogranin A and c-kit were occasionally positive in undifferentiated tumor cells. The diagnosis of carcinosarcoma was made based on the concomitant presence of HCC and sarcomatous components, yet it is noteworthy that various types of tumor cells were observed.

[Current status and future of clinical kidney transplantation in Japan].

Kidney transplantation has been established to be the therapy for an end-stage renal disease. In Japan, living donor kidney transplantation is frequently performed (> 80%) because of a shortage of the deceased donors. The graft survival has been improved to 93.4% (5-year graft survival in living donor kidney transplantation after 2001). ABO-incompatible cases are increasing and more than 20% are ABO-incompatible in Japan (30% in our institution). In our institution, 225 kidney transplantations (182: living donors, 43: deceased donors) have been performed from 2004.4 to 2010.6. Although the graft survival is excellent, posttransplant infections including cytomegalovirus, EB virus and BK virus are problems which should be solved. For the safety of the recipients, we should use kidney grafts from brain-dead donors.

New prognostic factor influencing long-term survival of patients with advanced gallbladder carcinoma.

BACKGROUND: Although the safety of operations has generally improved in recent years, the mortality of extended operations for advanced gallbladder carcinoma (GBC) remains high, and the outcomes of patients with advanced GBC requiring major surgery are poor. In this study, a newly formulated original stage classification of advanced GBC was evaluated to clarify prognostic factors affecting long-term survival. METHODS: A total of 149 patients with resected GBC infiltrating beyond the propria muscle layer were analyzed retrospectively. These patients were classified into F0 (n = 50), F1 (n = 38), F2 (n = 38), and F3 (n = 23) according to the number of positive histopathologic factors, consisting of direct invasion to the liver, invasion to the hepatoduodenal ligament, and lymph node metastasis. Overall survival rates were compared with the Union Internationale Contre le Cancer TNM classification (6th edition). RESULTS: Overall 5-year survival rates of patients with F0, F1, F2, and F3 were 60%, 35%, 5%, and 0%, respectively. Significant differences were observed, except between F2 and F3. In 38 patients with F1, there were no significant differences between 13 patients with direct invasion to the liver, 4 patients with invasion to the hepatoduodenal ligament, and 21 patients with lymph node metastasis. Multivariate analysis revealed that F classification was the most important independent risk factor to predict survival. CONCLUSION: Patients with advanced GBC are expected to survive long if only 1 of hepatic invasion, hepatoduodenal ligament invasion, or lymph node metastasis is positive.

Laparoscopic-assisted distal pancreatectomy and nephrectomy from a live donor.

BACKGROUND: The simultaneous transplantation of pancreas and kidney from live donors is performed in select countries. One of the reasons for this reduced applicability is the invasiveness of the donor operation. We propose the method of laparoscopic-assisted operation to be performed on live donors with minimal invasion. METHOD: The donor was placed in the right lateral decubitus position. A 7-cm upper midline incision was made, and a handport was installed in addition to two or three 12-mm ports. After the removal of the left kidney graft, the spleen and the distal part of the pancreas were completely mobilized. The splenic vein and artery were identified and mobilized. The donor was then rotated to a supine position. Dissection of the pancreatic parenchyma using ultrasound shears and ligation of the splenic vessels were performed through midline incision under direct vision. The distal part of the pancreas and the spleen were extracted. RESULTS: Since December 2007, 3 donors have undergone this operation. In all 3 cases, the postoperative course was uneventful, and both the renal and pancreatic grafts functioned well. CONCLUSION: This technique is minimally invasive and safe, and may become the standard method of live donor operation for simultaneous pancreas-kidney transplantation.

Eleven cases of postoperative hepatic infarction following pancreato-biliary surgery.

BACKGROUND: Postoperative hepatic infarction is rare; therefore, clinical characteristics and outcomes of postoperative hepatic infarction after pancreatobiliary surgery have not been obvious. METHODS: Eleven patients encountered hepatic infarction after pancreato-biliary surgery. Management, clinical course, and outcome of these 11 patients were retrospectively analyzed. RESULTS: Possible causes of the hepatic infarction were inadvertent injury of the hepatic artery during lymph node dissection in five patients, right hepatic artery ligation in two patients, long-term clamp of the hepatic artery during hepatic arterial reconstruction in two patients, suturing for bleeding from the right hepatic artery in one patient, and celiac axis compression syndrome in one patient. Five of the 17 infarcts extended for one whole section of the liver, and distribution of the other 12 was less than one section. Ten patients discharged from hospital; however, one patient died of sepsis of unknown origin. CONCLUSIONS: Attention should be paid to inadvertent injury of hepatic artery to prevent hepatic infarction. Hepatic infarctions after pancreato-biliary surgery seldom extend to the entire liver and most of them are able to be treated without intervention.

Inferior head resection of the pancreas for intraductal papillary mucinous neoplasms.

BACKGROUND: Previous reports have suggested that patients with intraductal papillary mucinous neoplasm (IPMN) have a favorable prognosis after surgical resection. Thus, a variety of types of partial pancreatic resections have been advocated for treating these low-grade malignant tumors. However, the surgical outcome of IPMN after such limited pancreatectomy has not been fully clarified. METHODS: We performed a retrospective review of the clinicopathologic features and surgical outcome in 15 patients who underwent inferior head resection for IPMN at the Chiba University Hospital and National Cancer Center Hospital East between July 1994 and January 2007. RESULTS: There were 13 patients with noninvasive IPMNs (10 adenomas and 3 noninvasive carcinomas) and 2 patients with minimally invasive intraductal papillary mucinous carcinoma (minimally invasive IPMN). Complete tumor removal (R0 resection) was performed in four patients (80%) with intraductal papillary mucinous carcinoma. Subsequent pancreatoduodenectomy was performed in one patient because of noninvasive carcinoma with multiple mucous lakes in the pancreatic parenchyma. Values for N-benzoyl-L: -tyrosyl-p-aminobenzoic acid excretion test results before (n = 13) and after (n = 13) the operation were 70.7 and 66.1, showing no significant difference. The 2-h glucose levels in the 75 g oral glucose tolerance test before (n = 13) and after (n = 13) the operation were 133 and 146 mg/dl, respectively, showing no significant difference. Pancreatic fistula occurred in 7 (47%) patients. Overall morbidity and mortality rates were 67 and 0%, respectively. The overall 1-, 3-, 5-, and 10-year survival rates for the 15 patients were 100, 79, 79, and 71%, respectively. The 1-, 3-, 5-, and 10-year survival rates for patients with noninvasive IPMN (n = 13) and those with minimally invasive IPMN (n = 2) were 100, 92, 92, and 83%; and 100, 0, 0, and 0%, respectively. There was a significant difference in survival between patients with noninvasive IPMN and those with minimally invasive IPMN (p = 0.0005). No patient with noninvasive IPMN developed recurrent disease. One patient with minimally invasive IPMN died of recurrent peritoneal dissemination 18 months after margin-positive R1 resection. Two patients died of pancreatic ductal adenocarcinoma, 30 and 78 months after inferior head resection. CONCLUSIONS: Pancreatic endocrine and exocrine function was well preserved after inferior head resection. Pancreatic fistula occurred more frequently after inferior head resection than with conventional pancreatoduodenectomy. Patients with noninvasive IPMN had favorable survivals after this procedure. However, one patient with minimally invasive IPMN with margin-positive R1 resection died of recurrent disease. Thus, margin-negative R0 resection should be performed for IPMN.

Living donor pancreas transplantation in Japan.

BACKGROUND/PURPOSE: Living-donor pancreas transplants (LDPs) were introduced at Chiba-East National Hospital in 2004, and 12 LDPs have been performed at this institution to date. Based on the outcome of these 12 LDPs, the efficacy and safety of LDPs are herein discussed. METHODS: Twelve diabetic patients underwent LDPs; ten had simultaneous pancreas and kidney transplants from living donors, one had pancreas transplant after a kidney transplant from a living donor, and one had a pancreas transplant alone from a living donor. The donors were parents or brothers and the ABO blood types were incompatible in three LDPs. The procedures for the donor and recipient operations were performed according to the technique established by the University of Minnesota. Bladder drainage was used in 11 recipients and enteric drainage was used in one patient. Tacrolimus, basiliximab, mycophenolate mofetil, and prednisone were used for induction and immunosuppressive treatment. A splenectomy, double-filtered plasmapheresis, and plasma exchange were added in the ABO-incompatible LDPs. RESULTS: No complications were observed in the donors during hospitalization. The 1-year survivals of the patients, kidney grafts, and pancreas grafts were 100, 100, and 100%, respectively. The 3-year survivals were 91.7, 90, and 91.7%, respectively. Three patients developed leakage of pancreatic juice and one patient required a surgical procedure. Cytomegalovirus antigenemia was detected in five patients (42%). CONCLUSIONS: Based on the excellent outcome of the LDPs at this institution, LDPs is therefore expected to become a promising option for the treatment of patients with severe diabetes.