Liver transection using indocyanine green fluorescence imaging and hepatic vein clamping.

BACKGROUND: Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection. METHODS: Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon ), veno-occlusive regions (FIVO ) and ischaemic regions (FIIS ) were calculated using luminance analysing software. RESULTS: Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30-458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS /FINon was lower than median FIVO /FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication. CONCLUSION: ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.

Visualization of the leakage of pancreatic juice using a chymotrypsin-activated fluorescent probe.

BACKGROUND: Pancreatic fistula (PF) remains the most serious complication after digestive surgery. It is difficult to prevent because of the inability to visualize the leakage of pancreatic juice during surgery or to evaluate the protease activity of leaked fluid, which is responsible for PF formation. METHODS: The fluorescence intensities of a chymotrypsin probe (glutaryl-phenylalanine [corrected] hydroxymethyl rhodamine green with added trypsin) in pancreatic juice and in intestinal or abdominal fluids drained after pancreatic resection were evaluated. The chymotrypsin probe was sprayed on to filter papers that had been placed on the resected pancreatic stump in patients undergoing pancreaticoduodenectomy or central pancreatectomy. The ability of this technique to visualize the leakage of pancreatic juice and predict postoperative PF formation was assessed. RESULTS: The fluorescence intensity of the chymotrypsin probe in 76 fluid samples correlated positively with amylase levels (r(s) = 0.678, P < 0.001). The fluorescence patterns of the pancreatic stump were classified grossly into the three types: duct (fluorescence signal visualized only on the stump of the main pancreatic duct, 16 patients), diffuse (ductal stump and surrounding pancreatic parenchyma, 7) and negative (no fluorescence signal, 7). Symptomatic PFs developed in 13 of 23 patients with duct- or diffuse-type fluorescence, but in none of the seven patients with negative-type fluorescence (P = 0.008). CONCLUSION: The chymotrypsin probe enabled determination of the protease activity in drained pancreatic fluid samples and allowed real-time visualization of pancreatic juice leakage during surgery.

Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy.

BACKGROUND: Although intraoperative cholangiography has been recommended for avoiding bile duct injury during laparoscopic cholecystectomy, radiographic cholangiography is time consuming and may itself cause injury to the bile duct. Recently, a novel fluorescent cholangiography technique using the intravenous injection of indocyanine green (ICG) has been developed. METHODS: In 52 patients undergoing laparoscopic cholecystectomy, 2.5 mg ICG was injected intravenously 30 min before the patient entered the operating room or following intubation. A fluorescent imaging system, which consisted of a xenon light source and a laparoscope with a charge-coupled device camera that could filter out light wavelengths below 810 nm, was used. Fluorescent cholangiography was performed during dissection of Calot's triangle, and its ability to delineate biliary anatomy was compared with that of preoperative cholangiography. RESULTS: Fluorescent cholangiography delineated the cystic duct in all 52 patients, and the cystic duct-common hepatic duct junction was visible before dissection of Calot's triangle in 50 patients. Fluorescent imaging also identified all accessory bile ducts that had been diagnosed before surgery in eight patients. CONCLUSION: Fluorescent cholangiography enables real-time identification of biliary anatomy during dissection of Calot's triangle. This simple technique may become standard practice for avoiding bile duct injury during laparoscopic cholecystectomy, replacing radiographic cholangiography.

Possible underestimation of blood loss during laparoscopic hepatectomy.

Background: Previous studies have documented potential advantages of laparoscopic hepatectomy in decreasing blood loss compared with open surgery. This study aimed to compare intraoperative blood loss estimated using four different methods in open versus laparoscopic hepatectomy. Methods: Patients undergoing liver resection between 2014 and 2017 were evaluated prospectively, differentiating between the laparoscopic and open approach. Groups were compared using univariable and multivariable analyses. Intraoperative blood loss was estimated using three formulas based on the postoperative decreases in haematocrit, haemoglobin or red blood cell volume, and using the conventional method of the sum of suction fluid amounts and gauze weight. In addition, blood loss per hepatic transection area was calculated to compare groups. Results: Some 125 patients who underwent hepatectomy were selected, including 56 open hepatectomies and 69 laparoscopic liver resections. Intraoperative blood loss per hepatic transection area estimated by the conventional method was significantly less in the laparoscopic than the open group (3·6 (range 0·2-50·0) versus 6·6 (1·2-82·5) ml/cm2 respectively; P < 0·001). In contrast, there were no significant differences between groups in blood loss estimated based on the decrease in haematocrit (12·9 (0-65·2) versus 8·1 (0-123·7) ml/cm2; P = 0·818), haemoglobin or red blood cell volume. Blood loss estimation using three formulas showed significant linear correlations with the blood loss estimated by the conventional method in the open group (r s = 0·758 to 0·762), but not in the laparoscopic group (r s = -0·019 to 0·031). Conclusion: The conventional method of calculating blood loss in laparoscopic hepatectomy can underestimate losses.

Indocyanine green fluorescence-guided surgery after IV injection in metastatic colorectal cancer: A systematic review.

OBJECTIVE: Indocyanine green fluorescence-guided surgery (ICG-FGS) has emerged as a potential new imaging modality for improving the detection of hepatic, lymph node (LN), and peritoneal metastases in colorectal cancer (CRC) patients. The aim of this paper is to review the available literature in the clinical setting of ICG-FGS for tumoral detection in various fields of metastatic colorectal disease. METHODS: PubMed and Medline literature databases were searched for original articles on the use of ICG in the setting of clinical studies on colorectal cancer. The search terms used were "near-infrared fluorescence", "intraoperative imaging", "indocyanine green", "human" and "colorectal cancer". RESULTS: ICG fluorescence imaging (ICG-FI) is clearly supported as an intraoperative technique that allows the detection of additional superficial hepatic metastases of CRC. Data on the role of ICG-FI in the intraoperative detection of peritoneal metastases and LN metastases are scarce but encouraging and ICG-FI could potentially improve the staging and treatment of these patients. CONCLUSION: ICG-FI is a promising imaging technique in the detection of small infraclinic LN, hepatic, and peritoneal metastatic deposits that may allow better staging and more complete surgical resection with a potential prognostic benefit for patients.

Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.

Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-κB signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here we report novel mechanisms of HCC progression through Sharpin overexpression. In our study, Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that Versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in Sharpin-expressing stable cells. Versican expression increased in the majority of HCC tissues and knocking down of Versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of Versican transcription synergistically with Wnt/ß-catenin pathway activation. Furthermore, Sharpin-overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes Versican expression synergistically with the Wnt/ß-catenin pathway, potentially contributing to HCC development. A Sharpin/Versican axis could be an attractive therapeutic target for this currently untreatable cancer.

Optimal initial dose of orally administered cyclosporine following intravenous cyclosporine therapy.

Conversion of the main immunosuppressive agent from tacrolimus to cyclosporine (CyA) is a valuable rescue therapy for the severe adverse effects of tacrolimus. We report our experience of the conversion in living donor liver transplantation, in which tacrolimus therapy was converted to CyA. There are few reports describing the optimal initial dose of orally administered CyA (PO CyA) after intravenously administered CyA (IV CyA). We retrospectively investigated the ratio of CyA blood concentrations at 12 hours after the initiation of PO CyA to that just before the conversion, and the ratio of the initial dose of PO CyA to the total dose of IV CyA administered during the 12 hours before the conversion. Linear regression analysis revealed a close correlation between these ratios (y = 2.7 + 5.8x, r = 0.73; P = .002). We recommend that, to maintain a similar trough level of CyA during conversion in liver transplantation, Neoral should be initiated at a ninefold greater dose than the total dose of IV CyA administered during the 12 hours before conversion.

Effect of clavulanic acid on inactivated amoxicillin excretion in urinary tract infection.

Oral amoxicillin was taken with and without clavulanic acid by normal subjects and by patients with chronic complicated urinary tract infection to examine the in vitro protective effect of clavulanic acid on amoxicillin degradation. When amoxicillin alone was taken, urinary excretion of the penicilloic acid of amoxicillin in bacteria-positive patients was higher than that in bacteria-negative patients and in normal subjects. There was no comparable change in urinary penicilloic acid excretion in the presence of clavulanic acid. There were significant in vitro protective effects of clavulanic acid on beta-lactamases in the urine.

Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat.

A means of enhancing absorption of the antibiotic, fosfomycin, has been investigated using promoters in rat jejunum and colon. Polyoxyethylene lauryl ether (BL-9EX), saponin, the sodium salts of fatty acids and mixed micelles were effective at 1% in increasing fosfomycin absorption. Of the sodium salts of saturated medium-chain fatty acids examined, the strength of this effect was in the order caprate greater than laurate greater than caprylate. Mixed micelles, consisting of fusogenic lipids and sodium taurocholate, enhanced fosfomycin absorption independently of the degree of unsaturation of the lipids; their effectiveness far exceeded that of sodium taurocholate alone. The action of these promoters was more evident in the colon than in the jejunum, except for the sodium salts of bile acids and disodium ethylenediaminetetraacetate (EDTA-2Na). The effects of glycocholate and taurocholate were essentially the same at both absorption sites, but that of EDTA-2Na was much greater in the jejunum than the colon. Improved fosfomycin absorption was observed at more than 0.5% sodium caprate concentrations in both the jejunum and colon. BL-9EX was effective at 0.1% in the jejunum or at 0.05% in the colon. The effectiveness at these low concentrations demonstrates the practicality of promoters for improving fosfomycin absorption with only minor membrane damage, especially in the colon.

Squamous cell carcinoma arising in chronic perianal pyoderma a case report and review of Japanese literature.

We report a rare case of squamous cell carcinoma developing from fistules of chronic perianal pyoderma in a 49-year-old Japanese man. He first noticed an abscess and nodule on his buttocks and perianal area 21 year previously (at the age of 28); the fistules formed later. These fistules were surgically removed, and an artificial anus was constructed 14 years ago (at the age of 35) in our hospital, when a histopathological examination revealed no malignant changes. However, he was recently admitted to our hospital with arterial bleeding from the ulcer of the buttock. On admission, the histological diagnosis of the ulcer was well differentiated squamous cell carcinoma. Wide local excision of the ulcer and scar tissue, including the sacrum, was performed. The defect was covered with a left latissimus dorsi flap and skin graft. He received radiation therapy after the operation. However, he died of cachexia and pneumonia. This case indicated that the CPP would better have been treated with wide excision before the development of SCC. Therefore, we recommend careful follow-up of patients affected by CPP and repeated biopsies of the lesion, particularly when the condition is severe, longstanding, and extensive. We discussed the term "CPP" and reviewed 22 cases of SCC arising in CPP reported in the Japanese literature.

Sister Joseph's nodule: a case report and review of the Japanese literature.

We report a case of metastatic carcinoma on the umbilicus, which is known as Sister Joseph's nodule. A 65-year-old man with the chief complaint of a painful nodule on the umbilicus was referred to our hospital. Histopathological examination revealed moderately differentiated tubular adenocarcinoma in the dermis. Endoscopic examination found gastric cancer of Borrmann type IV. The umbilical lesion represented a metastasis from the gastric cancer. We reviewed 80 cases of metastatic carcinomas to the umbilicus that have been reported in the Japanese literature.

Pretibial myxedema with Graves' disease: a case report and review of Japanese literature.

We report a case of pretibial myxedema with Graves' disease in an 18-year-old Japanese woman. The physical examination revealed waxy indurated plaques with prominent hair follicle openings and nonpitting edema disseminated on her lower legs. Histology from an edematous lesion revealed that the dermis was markedly thickened with abundant mucin, especially hyaluronic acid, and the collagen fibers in this portion were splitting up into fibrils. We also reviewed 112 cases of pretibial myxedema reported in the Japanese literature.

[Antitumor effect of intermittent oral administration of UFT against human rectal cancer xenografted in nude mice].

Effect and toxicities of oral administration of UFT were examined with tumor xenografts (COK-7LiM) in nude mice. Special attention was paid to the differences between daily (Q1D X 9) and intermittent (Q4D X 3) treatments with this agent. The optimal doses of UFT were determined on the basis of the maximal tolerated dose of the agent in nude mice. It was remarkable that the chemotherapeutic effect by intermittent administration of UFT showed a significantly better result than that by daily administration. No difference was seen in the toxicities between the two methods of administration of UFT. Moreover, the concentration of 5-FU in the tumor tissue treated with UFT intermittently was significantly higher than that by daily administration method.

[A case of local recurrence of rectal cancer successfully treated by UFT combined with two-route CDDP chemotherapy under the AT-II induced hypertension].

A case of local recurrence of rectal cancer was successfully treated by UFT combined with two-route CDDP chemotherapy under the AT-II induced hypertension. UFT (600 mg/day) was orally administered every day. CDDP (75 mg/m2) was infused into the right internal iliac artery via subcutaneously grafted Infuse-a-port under hypertensive state induced by the AT-II (3 micrograms/min). Sodium thiosulfate was intravenously given to protect the CDDP induced nephrotoxicity. The recurrence tumor palpated by digital examination and revealed by MRI disappeared after the fourth two-route CDDP chemotherapy. The serum CEA level elevated before the treatment also normalized. This combined chemotherapy was considered to be an effective measure to cure the local recurrence of rectal cancer.

[Studies on 5-FU concentration and thymidine phosphorylase activity in tissues of patients with colorectal cancer after SF-SP administration].

5-fluorouracil (5-FU) concentrations in peripheral blood, portal blood, normal and cancer tissues were evaluated in 26 patients with colorectal cancer after SF-SP administration (800 mg/day for 10 days). Thymidine phosphorylase activity in cancer tissues was also evaluated. 5-FU concentration in cancer tissues was significantly higher than that in other three specimens, and much higher than 0.05 microgram/g which was reported to be the minimum effective concentration. 5-FU concentration in portal blood was lower than MEC (0.05 microgram/ml). As for the relationship with the pathological features of cancer, the protruding lesions showed a higher 5-FU concentration than the ulcerative ones, and the lesions invaded only to submucosa or proper muscle showed a higher concentration than others. 5-FU concentration ratio in cancer tissues per in peripheral blood (T/B ratio) was related to thymidine phosphorylase activity. The higher was the thymidine phosphorylase activity, the greater T/B ratio. The results suggest that the tumor with higher thymidine phosphorylase activity might have a more pronounced anticancer efficacy of 5-FU.

Indocyanine green fluorescence imaging in the surgical management of liver cancers: current facts and future implications.

Imaging detection of liver cancers and identification of the bile ducts during surgery, based on the fluorescence properties of indocyanine green, has recently been developed in liver surgery. The principle of this imaging technique relies on the intravenous administration of indocyanine green before surgery and the illumination of the surface of the liver by an infrared camera that simultaneously induces and collects the fluorescence. Detection by fluorescence is based on the contrast between the (fluorescent) tumoral or peri-tumoral tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine green fluorescence imaging is capable of identification of new liver cancers and enables the characterization of known hepatic lesions in real time during liver resection. The purpose of this paper is to present the fundamental principles of fluorescence imaging detection, to describe successively the practical and technical aspects of its use and the appearance of hepatic lesions in fluorescence, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver surgery.

Hepatocellular carcinoma: Western and Eastern surgeons' points of view.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Developed on a pathological liver in 90% of cases, theoretically liver transplantation (LT) is its best treatment because it cures both malignancy and cause of malignancy, the underlying pathological liver. Cadaveric donors are the main source of liver in Western countries as France and living donors are the rules in Eastern countries as Japan. Because organ shortage could impact choices in HCC treatments, it was interesting to compare a Western and Eastern surgeon's points of view about treatment of HCC to assess if the source of organs has modified therapeutic strategies. Hence, aim of this work was to compare points of view of two hepatobiliary and transplant surgeons specialized in the treatment of HCC in France and Japan concerning five keys points that are decisive to choose one of the two curative treatments in HCC on pathological liver: liver resection or LT. These questions included the definition of an oncological treatment of HCC, the assessment of liver function, the treatment of HCC recurrences, the incidence of pathological information on therapeutic strategy and potential future therapeutics strategies.

Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative regulator of HIF-1, through binding to pro-survival Bcl-2 family proteins.

Inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS) is a dominant negative transcription factor that represses hypoxia-inducible factor 1 (HIF-1) activity. In this study, we show that IPAS also functions as a pro-apoptotic protein through binding to pro-survival Bcl-2 family members. In a previous paper, we reported that NF-κB-dependent IPAS induction by cobalt chloride repressed the hypoxic response in PC12 cells. We found that prolonged incubation under the same conditions caused apoptosis in PC12 cells. Repression of IPAS induction protected cells from apoptosis. Furthermore, knockdown of IPAS recovered cell viability. EGFP-IPAS protein was localized in both the nucleus and the cytoplasm, with a large fraction associated with mitochondria. Mitochondrial IPAS induced mitochondria depolarization and caspase-3 activation. Immunoprecipitation assays revealed that IPAS is associated with Bcl-x(L), Bcl-w and Mcl-1. The association of IPAS with Bcl-x(L) was also observed in living cells by the FLIM-based FRET analysis, indicating direct binding between the two proteins. IPAS contributed to dysfunction of Bcl-x(L) by inhibiting the interaction of Bcl-x(L) with Bax. These results demonstrate that IPAS functions as a dual function protein involved in transcription repression and apoptosis.