Significance of sonic hedgehog signaling after massive hepatectomy in a rat

Purpose

To clarify the functional involvement of hedgehog signaling, especially sonic hedgehog (Shh) and glioma-associated oncogene (Gli)-1 which are known to play an important role in embryonic development and cancer, in the regeneration of a hepatectomized rat liver.

Methods

Six-week-old male Wistar rats were subjected to 70 or 90 % hepatectomy (Hx). Animals were killed at 24, 48 and 72 h after Hx. The liver/body weight ratio was measured as an index of regeneration. Formalin-fixed liver samples were embedded in paraffin, stained for immunohistochemistry with proliferating cell nuclear antigen (PCNA) antibody, and the labeling index was calculated. Immunohistochemistry was also performed with Shh and Gli-1 antibodies.

Results

The liver/body weight ratio gradually increased in both the 70 and 90 % Hx, groups. The hepatocytes were strongly stained for PCNA at 24 h after Hx. Non-parenchymal cells were gradually stained by PCNA from 24 to 72 h after Hx. Shh and Gli-1 expression in hepatocytes was higher after 24 h than at other times and then gradually decreased. Shh and Gli-1 expression in non-parenchymal cells increased gradually, and was found mainly in liver zone I at 72 h after 70 and 90 % Hx.

Conclusions

The expression of both markers suggested that Shh signaling contributes to tissue reconstruction after Hx.     

Expression of HGF and TGF-β1 mRNA after partial hepatectomy in rats with liver cirrhosis

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-₁ (TGF-₁) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-₁ in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl₄). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18 h after a 70% hepatectomy. The expression of TGF-₁ mRNA peaked at 18 h after partial hepatectomy in the LC group and at 48 h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-₁.     

Multiple low doses of erythropoietin delay the proliferation of hepatocytes but promote liver function in a rat model of subtotal hepatectomy

Purpose

The impact of various doses of erythropoietin (EPO) on liver regeneration after partial hepatectomy (PH) in different animal models is still under debate. We investigated the impact of low doses of EPO on liver regeneration in a rat model of subtotal hepatectomy.

Methods

We established a 90 % PH rat model with perioperative injections of low-dose EPO (1,000 IU/kg). We analyzed survival and hepatocyte proliferation in animals treated with or without EPO and assessed liver function by blood ammonia measurement and the indocyanine green 15-min retention test.

Results

Low doses of EPO treatment improved the survival of rats after 90 % PH. Unexpectedly, during the first 24 h after the operation, liver regeneration in the EPO-treated rats was inhibited. DNA synthesis, cell proliferation, and the expression of cyclins and p-STAT3 peaked 48 h after PH, which was delayed by about 24 h vs. the control rats. Furthermore, EPO treatment increased the serum level of IL-6 and protected the hepatocytes from apoptosis.

Conclusion

Low doses of EPO do not stimulate early hepatocyte proliferation in the regenerating liver, but contribute to liver protection by inducing IL-6 and inhibiting apoptosis.     

Effect of Donor Right Hepatectomy on Splenic Volume and Platelet Count for Living Donor Liver Transplantation

Background

Donor hepatectomy for living donor liver transplantation accompanies physio-morphological changes of the liver and spleen. Therefore, the long-term consequences of these organs should be characterized to ensure donor's safety.

Methods

A total of 382 right liver harvests for liver transplantation were performed from October 2000 to February 2011. Clinical parameters across donor operations were compared, and the associations were investigated.

Results

The remaining liver grew continually, reaching 81.5?±?11.2 % of the entire liver until 6 months after donation. The spleen grew to 143.1?±?28.8 % of the pre-donation value within 1 week after surgery, and thereafter, its size decreased gradually to 130.6?±?25.1 % at 6 months. At 6 months post-donation, 48.1 % (114/237) of donors showed an increase of ≥30 % in splenic volume, and 15.9 % (50/315) of donors exhibited a decrease of ≥30 % in platelet count. However, patients with splenic enlargement and/or decrease in platelet count at 6 months post-donation were not different in liver function, liver regeneration, or overall complications.

Conclusions

Although splenic enlargement and/or decrease in platelet count can persist for more than 6 months after donation in patient population after donor right hepatectomy, such a change did not impact donor's safety.     

Repeat Hepatectomy for Recurrent Liver Metastasis From Gastric Carcinoma

Background

The efficacy of repeat hepatectomy for recurrent hepatocellular carcinoma and colorectal liver metastases is widely accepted. However, the benefits of such treatment for intrahepatic recurrence of gastric cancer liver metastasis remain unknown. This study sought to clarify the survival benefit for patients undergoing repeat hepatectomy for gastric cancer liver metastasis.

Methods

A total of 73 patients underwent hepatectomy for gastric cancer liver metastasis from January 1993 to January 2011. Macroscopically curative surgery was performed in 64 patients. Among them, repeat hepatectomy was performed in 14 of the 37 patients with intrahepatic recurrence. Among these 14 patients, clinicopathologic factors were evaluated by univariate and multivariate analysis to identify the factors affecting survival.

Results

The overall 1-, 3-, and 5-year survival rates after a second hepatectomy were 71, 47, and 47 %, respectively. The median survival was 31 months. Operative morbidity and mortality rates of repeat hepatectomy were 29 and 0 %, respectively. Multivariate analysis identified the duration of the disease-free interval as the only independent significant factor predicting better survival.

Conclusions

In selected patients, repeat hepatectomy for recurrent gastric cancer liver metastasis may offer the same chance of cure as the primary hepatectomy. Disease-free intervals exceeding 12 months predict good patient survival after repeat hepatectomy.     

High Survival in Patients Operated for Small Isolated Liver Metastases from Gastric Cancer: A Multi-institutional Study

Background

Although several studies have reported the outcomes of surgery for the treatment of liver metastases of gastric cancer (GLM), indications for liver resection for gastric metastases remain controversial. This study was designed to identify prognostic determinants that identify operable hepatic metastases from gastric cancer and to evaluate the actual targets of surgical therapy.

Methods

Retrospective analysis was performed on outcomes for 24 consecutive patients at five institutions who underwent gastrectomy for gastric cancer followed by curative hepatectomy for GLM between 2000 and June 2012.

Results

Overall 5-year survival and median survival were 40.1 % and 22.3 months, respectively. Uni- and multivariate analyses showed that liver metastatic tumour size less than 5 cm was the most important predictor of overall survival (OS, p = 0.03). Four patients survived >5 years. Repeat hepatectomy was performed in three patients. Two of these patients have remained disease-free since the repeat hepatectomy.

Conclusions

GLM patients with metastatic tumour diameter less than 5 cm maximum are the best candidates for hepatectomy. Hepatic resection should be considered as an option for gastric cancer patients with liver metastases.     

Predictors of intraoperative blood loss in patients undergoing hepatectomy

Purpose

Despite recent advances in surgical techniques, blood loss can still determine the postoperative outcome of hepatectomy. Thus, the preoperative identification of risk factors predicting increased blood loss is important.

Methods

We studied retrospectively the clinical records of 482 patients who underwent elective hepatectomy for liver disease, and analyzed the clinicopathological and surgical parameters influencing intraoperative blood loss.

Results

Red cell transfusion was required for 165 patients (35 %). Based on blood transfusion requirement and hepatic failure, we estimated predictive cut-off values at 850 and 1500 ml. The factors found to be significantly associated with increased blood loss were as follows: male gender, obstructive jaundice, non-metastatic liver carcinoma, Child-Pugh B disease, decreased uptake ratio on liver scintigraphy, platelet count, or prothrombin activity, longer hepatic transection time, operating time, the surgeon’s technique, J-shape or median incision, major hepatectomy, and not using hemostatic devices (p < 0.05). Multivariate analysis identified male gender, low prothrombin activity, longer transection time, longer operation time, and not using hemostatic devices as factors independently associated with increased blood loss (p < 0.05).

Conclusions

Male gender and low prothrombin activity represent risk factors for increased blood loss during hepatectomy. Moreover, every effort should be made to reduce the transection and operating times using the latest hemostatic devices.     

Function and volume recovery after partial hepatectomy: influence of preoperative liver function, residual liver volume, and obesity

Background

The regenerative capacity of the liver is an essential pre-condition for the successful application of partial hepatectomy. However, the actual kinetics of functional recovery remains unspecified and no adequate tool for its clinical monitoring has yet been available.

Methods

Eighty-five patients receiving major hepatectomy were investigated from the preoperative evaluation until 12?weeks after surgery. Liver function was determined by the LiMAx test for the enzymatic capacity of cytochrome P450 1A2. Liver volume was determined by volumetric analysis of repeated computer tomography scans. Functional and volume recovery were compared during follow-up.

Results

Major hepatectomy decreased liver function capacity to 35.7?±?13.8?% of preoperative function. It was shown that functional recovery already reaches 77.2?±?33.5?% of preoperative values within 10?days. The actual kinetics were dependent from the type and extent of hepatectomy. Complete functional restoration was achieved within 12?weeks, while liver volume still remained at 73.2?±?14.8?% of preoperative. A constant but interindividually variable correlation between function and volume was observed at all points in time.

Conclusion

Partial hepatectomy leads to fast and complete functional recovery, while volume recovery is delayed and remains often incomplete. The functional recovery is mainly influenced by the preoperative liver function, the residual liver volume, and by obesity.     

Percentage of Future Liver Remnant Volume Before Portal Vein Embolization Influences the Degree of Liver Regeneration After Hepatectomy

Background

Clinical determinants of liver regeneration induced by portal vein embolization (PVE) and hepatectomy remain unclear. The aims of this study were to investigate how liver regeneration occurs after PVE followed by hepatectomy and to determine which factors strongly promote liver regeneration.

Methods

Thirty-six patients who underwent both preoperative PVE and major hepatectomy were enrolled in this study. Percentage of future liver remnant volume before PVE (%FLR-pre) was compared with the remnant liver volume after PVE (%FLR-post-PVE) and on postoperative day 7 after hepatic resection (%FLR-post-HR). Clinical indicators contributing to liver regeneration induced by both PVE and hepatectomy were examined by logistic regression analysis.

Results

PVE and hepatectomy caused a two-step regeneration. FLR-pre, FLR-post-PVE, and FLR-post-HR were 448, 579, and 761 cm³, respectively. The %FLR-pre was significantly associated with liver regeneration induced by both PVE and hepatectomy (r?=?0.63, p?<?0.0001). Multiple regression analysis showed that only %FLR-pre was independently correlated with posthepatectomy liver regeneration (p?=?0.027, odds ratio?=?13.8).

Conclusion

After PVE and the subsequent hepatectomy, liver regeneration was accomplished in a two-step manner. Liver regeneration was strongly influenced by the %FLR-pre.     

Repeat Hepatectomy for Metastatic Colorectal Cancer Is Safe but Marginally Effective

Background

Although hepatectomy for metastatic colorectal cancer (mCRC) offers prolonged survival in up to 40% of people, recurrence rates are high, approaching 70%. Many patients experience recurrent disease in the liver after initial hepatectomy. We examined our experience with repeat hepatectomy for mCRC.

Methods

After Institutional Review Board approval, we reviewed the records of all patients at a single institution who underwent hepatectomy for mCRC. Repeat hepatectomy was defined as partial liver resection any time after the initial hepatectomy for recurrent mCRC. We estimated time to recurrence and survival by using the Kaplan?CMeier method and compared outcomes between groups by using the log-rank test.

Results

From 1998 to 2008, 405 patients underwent hepatectomy for mCRC, and 215 (53%) experienced disease recurrence at a median of 13?months. Of 150 patients with liver-only or liver-predominant recurrence, 52 (35%) underwent repeat hepatectomy. The median time to recurrence after repeat hepatectomy was 10?months, and median overall survival was 19?months. There was one (1.9%) perioperative death, and there were 14 (27%) major complications. The median overall survival in the repeat hepatectomy group from the time of recurrence after initial hepatectomy was 22?months, compared with 15?months in the 98 patients with liver recurrence who were not selected for repeat hepatectomy (P?=?0.02).

Conclusions

Repeat hepatectomy for mCRC is feasible in highly selected patients, with acceptable perioperative morbidity and mortality. Although repeat hepatectomy should be considered, recurrence rates are high. Although the initial hepatectomy for mCRC is potentially curative, recurrence of metastatic disease in the liver is unlikely to be cured.     

Resection Margin with Anatomic or Nonanatomic Hepatectomy for Liver Metastasis from Colorectal Cancer

Background

When hepatectomy is used as a primary treatment for liver metastasis from colorectal cancer (CRCLM), the balance between surgical curability and functional preservation of the remnant liver is of great importance.

Methods

A total of 108 patients who underwent initial hepatectomy for CRCLM were retrospectively analyzed with respect to tumor extent, operative method, and prognosis, including recurrence.

Results

The 1-, 2-, 3-, and 5-year overall survival rates (OS) for all patients were 90.5%, 77.8%, 63.2%, and 51.6%, respectively. Multivariate analysis indicated serum carbohydrate antigen 19-9 (CA 19-9) level after hepatectomy (<36 or ??36?mAU/mL) and presence of recurrence as independent prognostic factors of OS (P?=?0.0458 and 0.0249, respectively), and tumor depth of colorectal cancer (P?=?0.0025 and 0.00138, respectively). Neither resection margin nor type of hepatectomy (anatomic or nonanatomic) for CRCLM was a significant prognostic factor for OS or DFS or CRCLM recurrence, including intrahepatic recurrence.

Conclusions

In CRCLM, we believe that nonanatomic hepatectomy with narrow margin is indicated, and optimal treatment would include functional preservation of as much of the remnant liver as possible.     

Extending the limitations of liver surgery: outcomes of initial human experience in a high-volume center performing single-port laparoscopic liver resection for hepatocellular carcinoma

Background

Single-port laparoscopic surgery is slowly but steadily gaining popularity among surgeons performing minimally invasive abdominal surgeries. The aim of the present study is to assess our initial experience with single-port laparoscopic liver resection for hepatocellular carcinoma.

Methods

Between March 2009 and April 2011, 24 patients underwent single-port laparoscopic liver resection for hepatocellular carcinoma. Of these, 13 were laparoscopic segmentectomies, 4 were laparoscopic left lateral sectionectomies, 1 was a right hepatectomy, 1 was a left hepatectomy, and 4 were nonanatomical resections.

Results

Median operating time and blood loss were 205?min (95–545?min) and 500?ml (100–2,500?ml), respectively. Two procedures were converted to multiport laparoscopic hepatectomy due to instrument length limitations, and four were converted to open surgery. There were no serious intraoperative or postoperative complications in this series. Median postoperative stay was 8.5?days (5–16?days).

Conclusions

Although the procedure requires a lot of technical expertise added to the skill of liver surgery, single-port laparoscopic liver resection for hepatocellular carcinoma seems a feasible approach in a variety of well-selected cases. In spite of the demanding nature of the procedure and the requirement of better instrumentation for single-port laparoscopic surgery, the results seem to compare favorably with conventional laparoscopic surgery and open surgery.     

Hepatectomy based on the tumor hemodynamics for hepatocellular carcinoma: a comparison among the hybrid and pure laparoscopic procedures and open surgery

Purpose

This study was designed to evaluate the surgical parameters and treatment outcomes of tumor hemodynamics-based pure laparoscopic (PURE) and laparoscopy-assisted (HYBRID) hepatectomy for small hepatocellular carcinoma (HCC) compared with those of open hepatectomy.

Methods

Using a prospectively collected database from 1997 to 2011, we analyzed the data of 56 consecutive cases of laparoscopic hepatectomy for HCC (PURE, n = 24; HYBRID, n = 29; HALS, n = 3) from among 102 cases undergoing laparoscopic hepatectomy. We employed 27 cases treated by open hepatectomy during the same period as controls.

Results

PURE was associated with lesser blood loss, lower weight of the resected liver, and a shorter skin incision than HYBRID and open hepatectomy [median blood loss (mL): PURE 7, HYBRID 380, Open 450; P < 0.05]. On the other hand, HYBRID hepatectomy was associated with a longer operation time [operation time (min): HYBRID 232, Open 185; P = 0.0226]. The length of hospitalization in the cases treated by PURE and HYBRID hepatectomy was shorter than that in the cases treated by open hepatectomy [length of hospitalization (days): PURE 11, HYBRID 12, Open 17; P < 0.05]. One case each of transfusion and morbidity was recorded in this series. There was no significant difference of the overall (OS) or disease-free survival (DFS) between the patients treated by laparoscopic and open hepatectomy (3-year OS: 100 vs. 100 %; DFS 50 vs. 62 %, respectively).

Conclusions

Neither the surgical parameters nor the treatment outcomes of hemodynamics-based laparoscopic hepatectomy were inferior to those of open hepatectomy.     

Predictors for Early Recurrence After Hepatectomy for Initially Unresectable Colorectal Liver Metastasis

Background

Early recurrence correlates with poor survival following various cancer surgeries and puts considerable stress on patients both physically and mentally. This retrospective study investigated the predictive factors for early recurrence after surgical resection for initially unresectable colorectal liver metastasis to elucidate indications for conversion strategies.

Methods

We retrospectively studied 46 patients who underwent hepatectomy after chemotherapy for initially unresectable colorectal liver metastasis from 1997 to 2010.

Results

Recurrences occurred within 6 months after hepatectomy in 13 patients (37 %). The median survival time of 21.2 months and the 5-year survival rate of 0 % after hepatectomy in patients with recurrence within 6 months were significantly worse than those in patients with recurrence more than 6 months after hepatectomy. Recurrence in less than 6 months was significantly correlated with impossibility of anticancer therapy for recurrence after hepatectomy (p?=?0.01). Eight or more hepatic tumors after chemotherapy were the only predictor of recurrence within 6 months (p?=?0.01; odds ratio 9.6; 95 % confidence interval 1.5–60.6).

Conclusion

Recurrence within 6 months was significantly correlated with a poorer outcome following surgery for initially unresectable colorectal liver metastasis. Surgical indication for initially unresectable colorectal liver metastasis with eight or more hepatic tumors after chemotherapy should be considered carefully in the light of mental and physical status, co-morbidity, and alternative treatment plans.     

Inferior Right Hepatic Vein-preserving Major Right Hepatectomy for Hepatocellular Carcinoma in Patients with Significant Fibrosis or Cirrhosis

Background

Liver resection represents a most effective treatment for hepatocellular carcinoma (HCC). The extent of hepatectomy for HCC involves maintaining a tricky balance between radical resection of tumors and preservation of sufficient liver parenchyma. Generally, removal of the right hepatic vein often involves resection of the whole posterior right lobe, which may prevent patients with impaired liver function from maintaining a functional reserve and could also limit the future liver remnant from curative hepatectomy. As a common anatomic variation, preservation of the inferior right hepatic vein (IRHV) may enable preservation of liver segment 6, even when the right hepatic vein has to be removed. In the present study, we report our experience with IRHV-preserving major right hepatectomy.

Methods

From February 2009 to December 2011, eight trisegmentectomies 5-7-8 and two segmentectomies 4-5-7-8 were performed with the IRHV-sparing technique on patients with HCC and significant fibrosis or cirrhosis. Data including demographic information, preoperative evaluations, postoperative outcomes, and follow-up results were collected and evaluated.

Results

All patients survived and recovered from hepatectomy. The incidence of complications was higher in cirrhotic patients. The 1-year overall survival rate was 80 %, and the 1-year disease free survival rate was 60 %.

Conclusions

IRHV-preserving major right hepatectomy increases the resectability of HCC. Intraoperative ultrasonography is recommended to facilitate protection of the IRHV. This technique is safe with careful preoperative evaluation and meticulous perioperative care. The short-term outcome of IRHV-preserving liver resections is satisfactory.     

Pancreatic injury after major hepatectomy: a study in a porcine model

Purpose

The aim of this study was to investigate the pathophysiology of pancreatitis after major hepatectomy.

Methods

The study used ten female pigs. Three served as sham animals (sham group) and were killed after laparotomy to obtain normal tissue samples. Seven animals were subjected to major hepatectomy (70–75%), using the Pringle maneuver for 150?min, after constructing a portacaval side-to-side anastomosis (hepatectomy group). Duration of reperfusion was 24?h.

Results

Pancreatic tissue sampled 24?h after reperfusion had increased necrosis and edema in comparison to sham group and to tissue sampled at 12?h. Tissue malondialdehyde (MDA) did not differ significantly between samples at 12 and 24?h but was increased in the hepatectomy group in comparison to sham animals. Percentage increase in portal MDA content during reperfusion was greater at 12?h of reperfusion in comparison to the increase after 24?h. Portal pressure increased significantly after 12?h of reperfusion. Serum amylase and C-peptide increased during reperfusion in comparison to baseline levels.

Conclusions

The findings suggest that intraoperative portal congestion is not the only cause of the development of pancreatitis after major hepatectomy. The oxidative markers suggest that reactive oxygen species produced during vascular control may be responsible as well.     

Clinicopathological Features of Recurrence in Patients After 10-year Disease-free Survival Following Curative Hepatic Resection of Hepatocellular Carcinoma

Background

The present study aimed to clarify the clinicopathologic features of long-term disease-fee survival after resection of hepatocellular carcinoma (HCC).

Methods

This retrospective study identified 940 patients who underwent curative resection of HCC between 1991 and 2000 at five university hospitals. Seventy-four patients with 10 years of recurrence-free survival were identified and followed up. They were divided into two groups, 60 recurrence-free and 14 with recurrence after a 10-year recurrence-free period.

Results

Overall survival rates of recurrence and non-recurrence groups were 68 and 91 % at 16 years, and 34 and 91 % at 20 years (p = 0.02), respectively. There were five (36 %), and two deaths (3 %), respectively, after 10 recurrence-free years. A second resection for recurrence was performed in four patients (29 %), and mean survival was 15.3 years after the first hepatectomy. Although three patients in the non-recurrence group (5 %) developed esophageal and/or gastric varices, seven patients in the recurrence group (50 %) developed varices during 10 years (p < 0.0001). In multivariate analysis, preoperative and 10-year platelet count was identified as a favorable independent factor for maintained recurrence-free survival after a 10-year recurrence-free period following curative hepatic resection of HCC.

Conclusions

Recurrence of HCC may occur even after a 10-year recurrence-free period. Long-term follow-up after resection of HCC is important, and should be life-long. Patients with higher preoperative and 10-year platelet counts are more likely to have long-term survival after resection. A low platelet count, related to the degree of liver fibrosis, is a risk factor for recurrence and survival of HCC after curative resection.     

Liver-to-Spleen Ratio as an Index of Chronic Liver Diseases and Safety of Hepatectomy: A Pilot Study

Background

Hepatic failure is a main cause of death after hepatectomy. Accurate preoperative evaluation of functional liver reserve is the key to ensure safe resection. Studies have found that the spleen would gradually enlarge as chronic liver disease worsened. This study was designed to determine whether preoperative liver-to-spleen ratio (LSR) would be an indicator to evaluate severity of liver disease and predict safety of hepatectomy.

Methods

The volumes of liver and spleen were evaluated on computed tomography scan in 67 patients who received partial hepatectomy. Preoperative LSR was calculated. Statistical analysis was conducted to examine the relationship between LSR and the degree of chronic liver disease. Ability of LSR to predict the safety of hepatectomy also was evaluated.

Results

LSR had a negative correlation with the degree of chronic liver diseases (r = ?0.606, P < 0.0001). LSR = 3.22 was the cutoff point for predicting posthepatectomy complications and inadequacy. AUC, sensitivity, and specificity for predicting posthepatectomy complications and inadequacy respectively were 0.830 (95 % confidence interval [CI] 0.715–0.950, P < 0.0001), 69.6, 93.2 %, and 0.863 (95 % CI 0.777–0.949, P < 0.0001), 68.8, 84.3 %. Multivariate analysis showed that LSR = 3.22 was the factor that affected both posthepatectomy complications and liver inadequacy.

Conclusions

Preoperative LSR score correlated well with the degree of chronic liver diseases, and it probably help us to improve the safety of hepatectomy.     

The separate and combined influence of antioxidant and anti-inflammatory drugs on the liver during ischaemia-reperfusion of the superior mesenteric artery: An experimental study

Aim-Background

To investigate the influence of N-acetyl-cysteine (NAC) and Atorvastatin, separately and combined, on the liver of rats after inducing ischaemia-reperfusion of the superior mesenteric artery.

Methods

Forty male rats aged 2½ months and weighing 220–250gr were randomly assigned to 5 groups of 8 rats. The rats in the first group were considered as controls. The second group was subjected to ischaemia of the superior mesenteric artery for 45 minutes, followed by reperfusion of the superior mesenteric artery for 3 hours, without any drug administration. In the third group, a single dose of Atorvastatin (10mg/kg) was administered 24 hours before the phase of ischaemia. The fourth group received a single dose of N-acetyl-cysteine (160mg/kg) 24 hours before the phase of ischaemia. The fifth group was given both drugs simultaneously 24 hours before the phase of ischaemia. Three hours after reperfusion of the superior mesenteric artery, the liver was surgically removed and prepared for histological examination.

Results

The histological examination of liver tissue samples revealed diffuse necrosis of hepatocytes in the group without any drug administration prior to ischaemia-reperfusion. The groups of animals that were treated with NAC or Atorvastatin or the combination of both drugs showed quite a different histological picture with focal necrosis of hepatocytes and less degenerative lesions.

Conclusions

This study shows that pretreatment with NAC, Atorvastatin and their combination protects the liver from injury induced by intestinal ischaemia-reperfusion. This is ascribed to the antioxidant and anti-inflammatory effect of the above-mentioned drugs.     

Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy

Background

Although laparoscopic hepatectomy has increasingly been used to treat cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to that of open surgery because the ability to visualize and palpate the liver surface during laparoscopy is relatively limited. Fluorescence imaging has the potential to provide a simple compensatory diagnostic tool for identification of cancers in the liver during laparoscopic hepatectomy.

Methods

In 17 patients who were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine green (ICG) was administered intravenously within the 2 weeks prior to surgery. Intraoperatively, a laparoscopic fluorescence imaging system obtained fluorescence images of its surfaces during mobilization of the liver.

Results

In all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs (75 %) and 11 LMs (69 %) on the liver surfaces distributed over Couinaud’s segments 1–8, including the 17 tumors that had not been identified by visual inspections of normal color images. The 23 tumors that were identified by fluorescence imaging were located closer to the liver surfaces than another nine tumors that were not identified by fluorescence imaging (median [range] depth 1 [0–5] vs. 11 [8–30] mm; p < 0.001).

Conclusions

Like palpation during open hepatectomy, laparoscopic ICG fluorescence imaging enables real-time identification of subcapsular liver cancers, thus facilitating estimation of the required extent of hepatic mobilization and determination of the location of an appropriate hepatic transection line.