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.

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.

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.

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.

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.

Microbiological profile of donor corneas stored for tectonic transplantation purposes in rabbits / Microbiologia de amostras de bancos de córneas destinadas a transplantes, em coelhos

This study aimed to evaluate the microbiota of donor rabbit corneas stored for tectonic transplantation purposes. Swabs from both corneas of 20 rabbits were carefully collected and submitted to microorganism isolation and identification. After this first swab collection, rabbits were euthanized for reasons other than this project and the eyes were enucleated. The corneas were collected and stored to compose the cornea tissue bank. Corneas were stored in a 0.3% tobramycin solution at -20ºC. After 30 days, the corneas were thawed at room temperature and removed from the antibiotic. New swabs were obtained from the corneas and submitted to microorganism isolation and identification. Gram positive organisms were predominant in the rabbit corneal flora before storage and the Staphylococcus sp. was the most common microorganism isolated from those samples. No growth was observed on the samples collected after storage. The methods used for collection and storage of the corneas were efficient to constitute a sterile donor corneal tissue bank.

Analisaram-se córneas armazenadas para transplantes tectônicos usando-se suabes coletados de 20 coelhos, visando ao isolamento e à identificação de microrganismos. Após a coleta das amostras, os coelhos foram submetidos à eutanásia, por razões alheias ao estudo, e enucleados. As córneas foram coletadas e armazenadas a fim de se constituir o banco de córneas. O armazenamento deu-se em solução de tobramicina 0,3% a -20ºC, por 30 dias. Após esse período, as córneas foram descongeladas à temperatura ambiente e removidas da solução de antibiótico. Novos suabes foram coletados e submetidos ao isolamento e à identificação dos microrganismos. A flora corneal mostrou-se predominantemente composta por bactérias Gram positivas, sendo o Staphylococcus sp. o mais identificado. Não se verificou crescimento de colônias bacterianas ou fúngicas nas amostras após o armazenamento. Considerando-se a maneira como a pesquisa foi concebida e as injunções do meio em que ela foi realizada, há como admitir, pela ausência de crescimento microbiano nas amostras armazenadas, que a técnica de armazenamento empregada é segura para a estocagem de córneas destinadas a transplantes.

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.

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.

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.

Mineral characteristics of leaves of plants from different phylogeny grown in various soil types in the temperate region.

The objective of this research was to analyze selected minerals in leaves of plants, belonging to 166 species growing in alluvial, low pH, brown forest and serpentine soils. Mineral characteristics of the soils involved were also determined. For the macronutrients, in trees grown in alluvial soil, N, P, Ca, and Mg concentrations of leaves were higher in recently evolved plants than in plants with a longer period of evolution; K concentration remained constant regardless of evolution. In grasses grown in alluvial soil, it was difficult to detect the general tendency of mineral concentration. N, P, and K concentrations in alluvial soil were closely related to those in low pH and serpentine soils. Ca concentration in alluvial soil was lower than that in low pH and serpentine soils. Mg concentration in alluvial soils was higher than that in low pH soils, while lower than that in serpentine soil. Therefore, N, P, and K accumulated according to the plant characteristics for these elements, while Ca and Mg accumulation was strongly affected by the soil properties. For the micronutrients, in trees, Fe and Mn remained constant regardless of evolution; Zn concentration was lower in recently-evolved plants than in plants with a longer period of evolution. In grasses, Fe, Mn, and Zn concentrations in Caryophyllids were high. Except for Caryophyllids, Fe and Cu concentrations remained constant. Mn concentration decreased with evolution, Zn concentration was higher in recently-evolved plants than in plants with a longer period of evolution.

Mineral characteristics of the leaves of 166 plant species with different phylogeny in the temperate region.

The P-N regression coefficient was moderate in Magnoliales, Coniferopsidae, Pteridophyta, and Asterids, but very high in Caryophyllids, and very low in Rosids. The K-N regression coefficient in trees remained constant regardless of evolution, and that in grasses was high except for Rosids compared with that in trees. The coefficient was very high in Caryophyllids and was very low in Rosids. The N-Ca and N-Mg relationship was not estimated at all, suggesting that the mechanism of Ca and Mg accumulation was completely different from that of N related accumulation. The Zn and Cu concentrations were related to the N concentration. The Al concentration in leaves was negatively correlated with the N, P, K, Ca, Mg, Na, Cu, Zn, Mn, and Fe concentrations, while the N, P, K, and Mn concentrations in leaves increased slightly with the increase of Al concentration in the high Al concentration. The Na concentration in leaves related negatively to the P, Ca, Cu, Zn, Mn and Al concentration range. Thus, it was demonstrated that most of the minerals in leaves accumulate negatively Al and Na indicating that there are antagonistic mechanisms for mineral accumulation in leaves among Al or Na and other mineral elements.

Patterns of pelvic invasion are prognostic in the treatment of locally recurrent rectal cancer.

BACKGROUND: Local recurrence of rectal cancer after curative resection remains a difficult clinical problem. The aim of this study was to elucidate prognostic risk factors after resection of recurrent cancer. METHODS: Between January 1983 and December 1999, 83 patients with locally recurrent rectal cancer were studied retrospectively for survival benefit by re-resection. Sixty patients underwent resection for recurrent cancer, including total pelvic exenteration in 30 patients and sacrectomy in 23 patients. The extent of locally recurrent tumour was classified by the pattern of pelvic invasion as follows: localized, sacral invasion and lateral invasion. RESULTS: Multivariate analysis showed that the pattern of pelvic invasion was a significant prognostic factor which independently influenced survival after resection of recurrent cancer (P < 0.001). The 5-year survival rates were 38 per cent in the localized type (n = 27), 10 per cent in the sacral invasive type (n = 16) and zero in the lateral invasive type (n = 17). CONCLUSION: Resection for locally recurrent rectal cancer is potentially curative in patients with localized or sacral invasive patterns of recurrence. Alternatives should be explored in patients with recurrence involving the lateral pelvic wall.

6-Substituted 2,2-bis(fluoromethyl)-benzopyran-4-carboxamide K+ channel openers.

In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N-(2-cyanoethyl)-2,2-bis(fluoromethyl)-6-pentafluoroethyl-2H-1-ben zopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 (13f) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol.

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.