[Show abstract][Hide abstract] ABSTRACT: Renal cell cancer (RCC) is one of the most frequent primary sites for metastatic pancreatic tumors although metastatic tumors are rare among pancreatic malignant tumors. The purpose of this study is to disclose the characterization and treatment outcomes of pancreatic metastases from RCC.
Of 262 patients with metastatic RCC treated at our hospital between 1999 and 2013, the data of 20 (7.6%) who simultaneously developed or subsequently acquired pancreatic metastases were retrospectively reviewed and statistically analyzed.
The median follow-up period from RCC diagnosis and pancreatic metastases was 13.4 years (inter-quartile range: IQR, 7.8-15.5 years) and 3.8 years (IQR, 2.1-5.5 years), respectively. Median duration from diagnosis of RCC to pancreatic metastasis was 7.8 years (IQR, 4.2-12.7 years). During this observation period, the estimated median overall survival (OS) time from the diagnosis of RCC to death or from pancreatic metastasis to death was not reached. The probability of patients surviving after pancreatic metastasis at 1, 3, and 5 years was 100, 87.7, and 78.9%, respectively. The estimated OS period from the diagnosis of metastases to death of the patients with pancreatic metastasis was significantly longer than that of the patients with non-pancreatic metastasis (median OS 2.7 years) (P < 0.0001). Surgical management for pancreatic metastasis was performed in 15 patients (75%). When the median follow-up period for these surgeries was 3.5 years (IQR, 1.9-5.2 years), the estimated median recurrence-free survival was 1.8 years. For the patients with multiple metastatic sites, molecularly targeted therapies were given to six (30%) patients. When the median follow-up period was 4.1 years (IQR, 3.0-4.4 years), no disease progression was observed.
The pancreas is frequently the only metastatic site and metastasis typically occurs a long time after nephrectomy. The OS period of these patients is long and both surgical and medical treatment resulted in good outcomes.
BMC Cancer 12/2015; 15(1):1050. DOI:10.1186/s12885-015-1050-2 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Laparoscopic deroofing is widely used for the treatment of symptomatic polycystic liver disease (PCLD). However, bile leakage is a common complication of surgical management for PCLD. Until now, indocyanine green fluorescence imaging (IGFI) has played an active role in hepatobiliary surgery. Herein, we report the effective application of a laparoscopic fusion IGFI system, known as PINPOINT, for laparoscopic deroofing.
In this study, we performed laparoscopic deroofing for PCLD using the laparoscopic fusion IGFI system. We conducted the procedure mainly under the normal view mode, occasionally switching to the fusion IGFI mode. First, we confirmed that the liver cysts did not contain bile using the fusion IGFI mode and then used a percutaneous puncture needle to remove the fluid from some of the giant cysts. Second, using the fusion IGFI mode, we were able to detect thin biliary branches and to adjust the division line of the cyst wall accordingly or, occasionally, to ligate the branches. Finally, we searched for and identified unexpected small bile leakage and then closed it using sutures.
The laparoscopic fusion IGFI system can simultaneously show fluorescent images, such as cholangiography and the liver parenchyma, on the normal color view. In the fusion IGFI mode, the intrahepatic bile duct and liver parenchyma can be easily discriminated in real time throughout the procedure. Accordingly, the laparoscopic fusion IGFI system is useful for the surgical treatment of PCLD, in which the boundary between the liver cysts and the liver parenchyma can otherwise be difficult to identify. This technique also enables the branches of Glisson's capsule to be identified without any other intervention.
The novel application of the laparoscopic fusion IGFI system allows reliable navigation for PCLD surgery.
[Show abstract][Hide abstract] ABSTRACT: Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the clinical and technical factors affecting the ability of fluorescence cholangiography (FC) using indocyanine green (ICG) to delineate the bile duct anatomy during laparoscopic cholecystectomy (LC).Application of FC during LC began after laparoscopic fluorescence imaging systems became commercially available.In 108 patients undergoing LC, FC was performed by preoperative intravenous injection of ICG (2.5 mg) during dissection of Calot's triangle, and clinical factors affecting the ability of FC to delineate the extrahepatic bile ducts were evaluated. Equipment-related factors associated with bile duct detectability were also assessed among 5 laparoscopic systems and 1 open fluorescence imaging system in ex vivo studies.FC delineated the confluence between the cystic duct and common hepatic duct (CyD-CHD) before and after dissection of Calot's triangle in 80 patients (74%) and 99 patients (92%), respectively. The interval between ICG injection and FC before dissection of Calot's triangle was significantly longer in the 80 patients in whom the CyD-CHD confluence was detected by fluorescence imaging before dissection (median, 90 min; range, 15-165 min) than in the remaining 28 patients in whom the confluence was undetectable (median, 47 min; range, 21-205 min; P < 0.01). The signal contrast on the fluorescence images of the bile duct samples was significantly different among the laparoscopic imaging systems and tended to decrease more steeply than those of the open imaging system as the target-laparoscope distance increased and porcine tissues covering the samples became thicker.FC is a simple navigation tool for obtaining a biliary roadmap to reach the "critical view of safety" during LC. Key factors for better bile duct identification by FC are administration of ICG as far in advance as possible before surgery, sufficient extension of connective tissues around the bile ducts, and placement of the tip of laparoscope close and vertically to Calot's triangle.
Medicine 06/2015; 94(25):e1005. DOI:10.1097/MD.0000000000001005 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the benefit of energy devices such as ultrasonically activated device and bipolar vessel sealing device in liver surgeries.
Several studies have suggested the benefit of energy devices in liver transection, while a randomized trial has found no association between their use and surgical outcomes.
Patients scheduled to undergo open liver resection were eligible for this multicenter non-blinded randomized study. They were randomized to receive an energy device (experimental group) or not (control group) during liver transection. The primary endpoint was the proportion of patients with intraoperative blood loss >1,000 mL. The primary aim was to show non-inferiority of hepatectomy with energy device to that without energy device.
A total of 212 patients were randomized and 211 (105 and 106 in the respective groups) were analyzed. Intraoperative blood loss >1,000 mL occurred in 15.0 % patients with energy device and 20.2 % patients without energy device. The experimental minus control group difference was -5.2 % (95 % confidence interval -13.8 to 3.3 %; non-inferiority test, p = 0.0248). Hepatectomy with energy device resulted in a shorter median liver transection time (63 vs. 84 min; p < 0.001) and a lower rate of postoperative bile leakage (4 vs. 16 %; p = 0.002).
The hypothesis that hepatectomy with energy device is not inferior to that without energy device in terms of blood loss has been demonstrated. The use of energy devices during liver surgery is clinically meaningful as it shortens the liver transection time and reduces the incidence of postoperative bile leakage.
World Journal of Surgery 01/2015; 39(6). DOI:10.1007/s00268-015-2967-y · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) during surgery for colorectal liver metastases (CRLM) when gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) is performed as a part of preoperative imaging work-up.
EOB-MRI is expected to supersede CE-IOUS, which is reportedly indispensable in surgery for CRLM.
One hundred consecutive patients underwent EOB-MRI, contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound within 1 month before surgery for CRLM. Conventional IOUS and subsequent CE-IOUS using perflubutane were performed after the laparotomy. All the nodules identified in any of the preoperative or intraoperative examinations were resected and were submitted for histological examination, in principle.
Preoperative imaging examinations identified 242 nodules; 25 additional nodules were newly identified using IOUS, 22 additional nodules were newly identified during CE-IOUS, and a histological examination further identified 4 nodules. Among the 25 nodules newly identified using IOUS, all 21 histologically proven CRLMs and 3 of the 4 benign nodules were correctly diagnosed using CE-IOUS. Among the 22 nodules newly identified using CE-IOUS, 17 nodules in 16 patients were histologically diagnosed as CRLMs. The planned surgical procedure was modified on the basis of IOUS and CE-IOUS findings in 12 and 14 patients, respectively. The sensitivity, positive-predictive value, and accuracy of CE-IOUS were 99%, 98%, and 97%, respectively. Those values of EOB-MRI (82%, 99%, 83%, respectively) were similar to CE-CT (81%, 99%, 81%, respectively).
CE-IOUS is useful in hepatic resection for CRLM, even if EOB-MRI and CE-CT are performed.
Annals of Surgery 01/2015; DOI:10.1097/SLA.0000000000001085 · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe the details of the surgical technique of pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD), using a supracolic anterior artery-first approach.
An artery-first approach in PD has been advocated in pancreatic cancer to judge resectability, clear the superior mesenteric artery margin from invasion, or reduce blood loss. However, the efficacy of an artery-first approach in mesopancreas dissection remains unclear.
This study involved 162 consecutive patients who underwent PD with curative intent. The patients were divided into 82 SMD-PDs and 80 conventional PDs (CoPD) and then stratified further according to the dissection level, that is, level 1 was applied to 24 simple mesopancreas divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a hemicircumferential superior mesenteric artery plexus resection to keep the margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results were collected to assess the feasibility and validity of SMD-PD with an artery-first approach.
Blood loss and operation duration were significantly less in the SMD-PD group than in the CoPD group among the total 162 patients. The imaging analysis showed that four fifths of pancreatic arterial branches came from the right dorsal aspect of the superior mesenteric artery and cancer abutment occurred exclusively from the same direction indicating the validity of an artery-first approach.
SMD-PD using an SAA is feasible across PD cases, with acceptable short-term outcomes, and we propose this procedure as a promising option for PD.
Annals of Surgery 01/2015; DOI:10.1097/SLA.0000000000001065 · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The efficacy of surgical resection for gastric cancer liver metastases (GCLMs) is currently debated. Hitherto, no large-scale clinical studies have been conducted.Methods
This retrospective multicentre study analysed a database of consecutive patients with either synchronous or metachronous metastases who underwent surgical R0 resection for GCLM between 1990 and 2010. Clinical data were collected from five cancer centres in Japan. Survival curves were assessed, and clinical parameters were evaluated to identify predictors of prognosis.ResultsA total of 256 patients were enrolled. The mean(s.d.) number of hepatic tumours resected was 2·0(2·4). The surgical mortality rate was 1·6 per cent. Median follow-up was 65 (range 1–261) months. Recurrences were detected in 192 patients (75·0 per cent). The median interval from hepatic resection to recurrence was 7 (range 1–72) months, and the dominant site of recurrence was the liver (72·4 per cent). Actuarial 1-, 3- and 5-year overall and recurrence-free survival rates were 77·3, 41·9 and 31·1 per cent, and 43·6, 32·4 and 30·1 per cent, respectively. Median overall and recurrence-free survival times were 31·1 and 9·4 months respectively. Multivariable analysis identified serosal invasion of the primary gastric cancer (hazard ratio (HR) 1·50; P = 0·012), three or more liver metastases (HR 2·33; P < 0·001) and liver tumour diameter at least 5 cm (HR 1·62; P = 0·005) as independent predictors of poor survival.Conclusion
Clinically resectable GCLM is rare, but strict and careful patient selection can lead to long-term survival following R0 surgical resection.
British Journal of Surgery 01/2015; 102(1). DOI:10.1002/bjs.9684 · 5.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Splenic vein ligation may result in sinistral (left-sided) portal hypertension and gastrointestinal haemorrhage. The aim of this study was to analyse the pathogenesis of sinistral portal hypertension following splenic vein ligation in pancreaticoduodenectomy.Methods
Patients who underwent pancreaticoduodenectomy for pancreatic cancer between January 2005 and December 2012 were included in this retrospective study. The venous flow pattern from the spleen and splenic hypertrophy were examined after surgery.ResultsOf 103 patients who underwent pancreaticoduodenectomy with portal vein resection, 43 had splenic vein ligation. There were two predominant venous flow patterns from the spleen. In the varicose route (27 patients), flow from the spleen passed to colonic varices and/or other varicose veins. In the non-varicose route, flow from the spleen passed through a splenocolonic collateral (14 patients) or a spontaneous splenorenal shunt (2 patients). The varicose route was associated with significantly greater splenic hypertrophy than the non-varicose route (median splenic hypertrophy ratio 1·52 versus 0·94; P < 0·001). All patients with the varicose route had colonic varices, and none had a right colic marginal vein at the hepatic flexure.Conclusion
Pancreaticoduodenectomy with splenic vein ligation may lead to sinistral portal hypertension. To avoid the development of varices, it is important to preserve the right colic marginal vein. Reconstruction of the splenic vein should be considered if the right colic marginal vein is divided.
British Journal of Surgery 12/2014; 102(3). DOI:10.1002/bjs.9707 · 5.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Recent studies suggest that systemic inflammatory response is closely associated with cancer patient prognosis. Although several inflammatory prognostic markers have been proposed, the data to support their validity are lacking in large Japanese cohorts.
This is a retrospective study to examine the prognostic value of inflammatory markers, such as C-reactive protein, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and modified Glasgow prognostic scale, in pancreatic cancer. Selection criteria were admittance to hospital between January 2008 and December 2012, histologically confirmed adenocarcinoma, diagnosis of invasive ductal pancreatic cancer compatible by computed tomography imaging, and followed-up until death or for 180 days or longer. The primary end point was overall survival, which was measured from the day of histological diagnosis.
There were 440 patients who met the selection criteria. Of the 440 cases, 200 (45.5%) received curative resection (166 Stage I/II and 34 Stage III patients), 237 (53.9%) received chemotherapy (4 Stage I/II, 92 Stage III and 141 Stage IV patients), and the remaining 3 received palliative care. Univariate and multivariate regression analyses revealed that advanced computed tomography stage, high level of C-reactive protein (0.45 mg/dl or greater), neutrophil-lymphocyte ratio (2.0 or greater) and CA19-9 level (1000 U/ml or greater) were significantly associated with worse prognosis.
We verified the results of previous studies, and showed that neutrophil-lymphocyte ratio and C-reactive protein also had prognostic value in a large Japanese PC cohort.
Japanese Journal of Clinical Oncology 10/2014; 45(1). DOI:10.1093/jjco/hyu159 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
A retrospective analysis indicated that the incidence of delayed gastric emptying (DGE) was less after using a circular stapler (CS) for duodenojejunostomy than that after hand-sewn (HS) anastomosis in pylorus-preserving pancreaticoduodenectomy (PpPD). This randomized clinical trial compared the incidence of DGE postoperative after CS duodenojejunostomy with that of conventional HS anastomosis in PpPD.
We randomly assigned 101 patients (age 20-80) undergoing PpPD to receive CS duodenojejunostomy (group CS, n = 50) or HS duodenojejunostomy (group HS, n = 51) in two Japanese cancer center hospitals between 2011 and 2013. The patients were stratified by institution and size of the main pancreatic duct (<3 or ≥3 mm). The primary endpoint was the incidence of grade B or C DGE according to the international definition with a non-inferiority margin of 5 %. This trial is registered with University hospital Medical Information Network (UMIN) Center: UMIN000005463.
Per-protocol analysis of data on 95 patients showed that grade B or C DGE was found in 4 (8.9 %) of 45 patients who underwent CS anastomosis and in 8 (16 %) of 50 patients who underwent HS anastomosis (P = 0.015). There were no differences in the overall incidence of DGE (P = 0.98), passage of the contrast medium through the anastomosis (P = 0.55), or hospital stays (P = 0.22).
CS duodenojejunostomy is not inferior to HS anastomosis with respect to the incidence of clinically significant DGE, justifying its use as treatment option.
Journal of the American College of Surgeons 10/2014; 219(4):e115. DOI:10.1016/j.jamcollsurg.2014.07.692 · 5.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The rate of recurrence after liver resection for colorectal liver metastases (CLM) is high, and repeat resection (RR) is reserved with curative intent in selected patients. This study evaluated the benefit of RR for recurrence after liver resection for CLM.
Data were collected on 287 consecutive patients who underwent primary curative hepatectomy between January 1999 and October 2008 for CLM at our institution.
After median follow-up of 63 months, 211 patients (73 %) developed recurrence and RR was conducted in 102 (48 %) patients. Five-year overall survival (OS) was significantly higher in the RR group than in those patients not selected for RR (70 vs. 45 %, P = 0.002). On multivariate analyses, RR was identified as an independent factor for good prognosis. According to the first recurrence sites, 5-year OS after recurrence was significantly better in patients with liver or lung only recurrence (55, 51 %, respectively) than in locoregional/lymph node metastases and other/multiple sites recurrence (33, 9.0 %, respectively). In patients with liver- or lung-only recurrence, 5-year OS after recurrence was significantly higher in RR patients than in those without RR (liver; 67 and 0 %, lung; 88 and 24 %, respectively; P
[Show abstract][Hide abstract] ABSTRACT: Objective: To investigate the feasibility and efficacy of anatomical liver resection (ALR) guided by fused images comprising a macroscopic view and indocyanine green fluorescence imaging (fusion IGFI). Background: ALR is established in treating hepatocellular carcinoma or other malignancies to achieve curability and functional preservation. However, the conventional demarcation technique (CDT) marks only the organ surface and sometimes fails to execute a completely valid demarcation. Methods: Twenty-four consecutive ALRs for focal liver malignancy were studied using fusion IGFI. Indocyanine green was administered systemically after selective inflow clamping in 12 patients or by portal puncture and direct injection in 12 patients, and we compared demarcation findings between fusion IGFI and CDT. The strength of contrast between target and nontarget areas was quantitatively calculated as contrast index and compared between IGFI and CDT according to injection technique or state of the liver surface. Results: Fusion IGFI achieved valid demarcation in 23 of 24 patients (95.8%), whereas CDT achieved valid demarcation in only 10 patients (41.7%) (P < 0.0001). The contrast index of fusion IGFI was 0.81 (0.18-2.51), which was significantly higher than that of CDT at 0.12 (0.01-0.42) (P < 0.0001), and the same result was obtained regardless of the injection method or liver surface state used. ALR was conducted referring to 3-dimensional staining of target parenchyma, with no related perioperative adverse events. Conclusions: Fusion IGFI is a safe imaging technique for ALR that attained valid 3-dimensional parenchymal demarcation with better feasibility and clearer demarcation than CDT. Copyright
Annals of Surgery 05/2014; 262(1). DOI:10.1097/SLA.0000000000000775 · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the molecular mechanism of desmoplastic reaction (DR) for providing aggressive tumor characteristics is increasingly recognized, the prognostic role of DR has not been investigated in colorectal liver metastasis (CRLM). A pathologic review of 412 patients who underwent hepatectomy for CRLM at 2 independent institutions was conducted. DR in primary tumors was classified as mature, intermediate, or immature on the basis of the existence of keloid-like collagen and myxoid stroma-distinctive histologic products of extracellular matrix remodeling. With respect to DR, 137, 122, and 153 patients were classified as mature, intermediate, and immature, respectively. Immature DRs were associated with higher T and N stages, higher primary tumor grade, synchronous and larger size of liver metastasis, and extrahepatic disease (P≤0.0001 to 0.002). DR significantly influenced the rate of recurrence in extrahepatic sites, including the lung, peritoneum, and local region in the primary tumor (P≤0.0001 to 0.03), rather than the remnant liver. Five-year overall survival rates after hepatectomy were the highest in the mature group (58.9%), followed by intermediate (42.1%) and immature (26.7%) groups. A significant prognostic impact of DR was observed in subset analyses for institutions, primary tumor location, and timing and number of liver metastases. Multivariate analysis revealed that DR was an independent prognostic factor along with T stage of the primary tumor, size of liver metastasis, and extrahepatic disease. Characterizing DR in the primary tumor on the basis of histologic products of cancer-associated fibroblasts is valuable in evaluating prognostic outcome after hepatectomy in CRLM patients.
The American journal of surgical pathology 05/2014; 38(10). DOI:10.1097/PAS.0000000000000232 · 5.15 Impact Factor