Takeaki Ishizawa

RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy.

Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway; however, no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1,053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival were estimated by the Kaplan‐Meier method and the log‐rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow‐up of 84.1 months (57.2—NA) for a survivor, the 4‐year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild‐type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and recurrence free survival. RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival.

Indocyanine green fluorescence imaging in colorectal surgery: overview, applications, and future directions

Indocyanine green fluorescence imaging is a surgical tool with increasing applications in colorectal surgery. This tool has received acceptance in various surgical disciplines as a potential method to enhance surgical field visualisation, improve lymph node retrieval, and decrease the incidence of anastomotic leaks. In colorectal surgery specifically, small studies have shown that intraoperative fluorescence imaging is a safe and feasible method to assess anastomotic perfusion, and its use might affect the incidence of anastomotic leaks. Controlled trials are ongoing to validate these conclusions. The number of new indications for indocyanine green continues to increase, including innovative options for detecting and guiding management of colorectal metastasis to the liver. These advances could offer great value for surgeons and patients, by improving the accuracy and outcomes of oncological resections.

Technical Details of an Anterior Approach to the Superior Mesenteric Artery During Pancreaticoduodenectomy.

IntroductionUse of central vascular ligation during dissection around the superior mesenteric artery (SMA) in pancreaticoduodenectomy (PD) for periampullary malignancies has rarely been documented.MethodsWe developed the SMA hanging technique (SHT) to facilitate central vascular ligation during PD. Briefly, SMA dissection was initiated using the supracolic anterior approach, followed by left-sided dissection. The SMA was taped under finger guidance immediately after right-sided dissection. The ligament of Treitz was detached from the SMA during left-sided dissection, facilitating adequate lymph node dissection while preserving the nerve plexus around the SMA. Forty-seven consecutive patients who underwent PD for periampullary malignancies were divided into two groups: 23 underwent SHT and 24 underwent conventional dissection. Patients’ clinical results were assessed to evaluate the feasibility and validity of SHT.ResultsBlood loss volume, operation duration, and the incidence of bleeding during SMA dissection were significantly lower in the SHT group than in the conventional group. The short-term and oncological results were similarly acceptable in both groups.ConclusionsSHT is a feasible and safe technique with acceptable short-term outcomes. We propose the use of this procedure to standardize en bloc dissection around the SMA.

Laparoscopic deroofing for polycystic liver disease using laparoscopic fusion indocyanine green fluorescence imaging

AbstractBackgroundLaparoscopic 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. MethodsIn 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.ResultsThe 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.ConclusionThe novel application of the laparoscopic fusion IGFI system allows reliable navigation for PCLD surgery.

History and Basic Technique of Fluorescence Imaging for Hepatobiliary-Pancreatic Surgery

Recently, fluorescence imaging using indocyanine green (ICG) has been used clinically to visualize the vascular/lymphatic anatomy and cancerous tissues in real time during surgery. Potentially, among the best indications for ICG fluorescence imaging are hepatobiliary and pancreatic diseases since not only the fluorescent property of ICG but also its biliary excretion property can be utilized for imaging. In fact, ICG fluorescence imaging is already being used in clinical settings to identify the anatomy of the bile duct during laparoscopic surgery as well as open surgery in cases of liver cancer. 5-aminolevulinic acid is another fluorescent probe that has been administered to humans for identification of malignant glioma, bladder cancer and epidermal tumor, although its application to hepatobiliary and pancreatic diseases has rarely been evaluated. Preclinically, numerous kinds of novel fluorescent probes are being developed to improve the sensitivity and specificity of ICG fluorescence imaging, making in vivo fluorescence imaging one of the most active research fields in the world.

Fluorescence Imaging of Human Bile and Biliary Anatomy

Intraoperative fluorescence images of the extrahepatic bile ducts can be obtained in real time by injecting indocyanine green (ICG) solution (0.025 mg/mL) directly into the biliary tract or by administering ICG (2.5 mg) intravenously. ICG is excreted into the bile and is fluoresced when protein bound. Fluorescence cholangiography by intravenous injection of ICG starts to prevail as a novel intraoperative navigation tool enabling visualization of the bile duct anatomy without any intervention to the bile ducts during laparoscopic cholecystectomy, and laparoscopic fluorescence imaging systems have become commercially available in 2010.

The need for “practical guidelines” of laparoscopic liver resection enabling appropriate patient selection

In 2014, the Second International Consensus Conference on Laparoscopic Liver Resection (2 nd ICCLLR) was held in Morioka, Japan, with the aim to provide recommendations for laparoscopic liver resection (LLR) through thorough review of previous literature followed by opinion exchange among experts of laparoscopic and open liver resection (OLR) (1). Recently, Cho and colleagues (2) have published a short review paper, entitled “practical guidelines for performing laparoscopic liver resection based on the second international laparoscopic liver consensus conference”.

Pancreatic Compression during Lymph Node Dissection in Laparoscopic Gastrectomy: Possible Cause of Pancreatic Leakage

Purpose Postoperative pancreatic fistula is a serious and fatal complication of gastrectomy for gastric cancer. Blunt trauma to the parenchyma of the pancreas can result from an assistants forceps compressing and retracting the pancreas, which in turn may result in pancreatic juice leakage. However, no published studies have focused on blunt trauma to the pancreas during laparoscopic surgery. Our aim was to investigate the relationship between compression of the pancreas and pancreatic juice leakage in a swine model. Materials and Methods Three female pigs were used in this study. The pancreas was gently compressed dorsally for 15 minutes laparoscopically with gauze grasped with forceps. Pancreatic juice leakage was visualized by fluorescence imaging after topical administration of chymotrypsin-activatable fluorophore in real time. Amylase concentrations in ascites collected at specified times was measured. In addition, pancreatic tissue was fixed with formalin, and the histology of the compressed sites was evaluated. Results Fluorescence imaging enabled visualization of pancreatic juice leaking into ascites around the pancreas. Median concentrations of pancreatic amylase in ascites increased from 46 U/L preoperatively to 12,509 U/L 4 hours after compression. Histological examination of tissues obtained 4 hours after compression revealed necrotic pancreatic acinar cells extending from the surface to deep within the pancreas and infiltration of inflammatory cells. Conclusions Pancreatic compression by the assistants forceps can contribute to pancreatic juice leakage. These findings will help to improve the procedure for lymph node dissection around the pancreas during laparoscopic gastrectomy.

Clinical implications of disappearing colorectal liver metastases have changed in the era of hepatocyte-specific MRI and contrast-enhanced intraoperative ultrasonography

BACKGROUND Clinical implication of disappearing liver metastases (DLMs) from colorectal cancer after chemotherapy needs to be reviewed in the era of modern imaging studies. METHODS Between 2010 and 2015, 184 patients underwent curative hepatectomy for colorectal liver metastases following preoperative chemotherapy. The sites of metastases detected on pre-chemotherapy CE-CT were examined post-chemotherapy using CE-CT, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), and contrast-enhanced intraoperative ultrasonography (CE-IOUS). DLMs were defined as tumors that disappeared on CE-CT post chemotherapy. The detection rate of DLMs with EOB-MRI and CE-IOUS were assessed, and the outcome of DLMs resected and those left in place were reviewed. RESULTS A total of 275 DLMs were noted in 59 patients. On EOB-MRI, 71 lesions (26%) were visible and were resected, 92% (65/71) of which contained viable disease. Using CE-IOUS, an additional 94 lesions were identified. A total of 165 DLMs (60%) were identified and resected by sequential use of EOB-MRI and CE-IOUS, 77% (127/165) of which contained viable disease. Of 110 DLMs not identified, 68 were resected, 4% (3/68) of which contained viable disease. Among 42 lesions left in place, 6 (14%) recurred during the median follow-up period of 27 (9-72) months. DISCUSSION EOB-MRI and CE-IOUS exploration identified clinically relevant DLMs containing viable disease with a high level of accuracy.

Intraductal papillary neoplasm of the bile duct found incidentally during examination of colonic disease: A case report

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a relatively rare bile duct neoplasm in the multistep carcinogenesis pathway towards cholangiocarcinoma. The diagnosis of IPNB is challenging, and its malignant potential means that its prognosis is related to the performance of R0 resection. We experienced a patient with IPNB detected during close examination of colonic disease and subsequently treated surgically. Case presentation: A 54-year-old man presented to an outside hospital with abdominal pain. Enhanced computed tomography showed wall thickening in the ascending colon and a cystic lesion close to the posterior segmental branch of the bile duct in the liver. Colonoscopy showed diverticulitis and severe stenosis in the ascending colon, with no finding of malignancy. Differential diagnosis of the liver tumor was IPNB, mucinous cystic neoplasm, or metastatic tumor from the colonic disease. The patient underwent hepatectomy and simultaneous right hemicolectomy for severe diverticulitis. Histopathological examination of the liver revealed IPNB with an associated invasive carcinoma. Conclusions: We report a relatively rare case of IPNB. Although preoperative diagnosis of IPNB remains challenging, complete resection is important for a favorable prognosis. Correspondence to: Akio Saiura, Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-831 Ariake, Koto-ku, Tokyo 135-8550, Japan, E-mail: saiura-tky@umin.ac.jp