Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection.

BACKGROUND: Drain amylase content in the days immediately after major pancreatic resection has been investigated previously as a predictor of postoperative pancreatic fistula (POPF). Its accuracy, however, has not been determined conclusively. The purpose of this study was to evaluate the accuracy of drain amylase content on the first day after major pancreatic resection in predicting the occurrence of POPF. METHODS: A literature search of the MEDLINE, Embase and Scopus(®) databases to 13 May 2015 was performed to identify studies evaluating the accuracy of drain amylase values on day 1 after surgery in predicting the occurrence of POPF. The area under the hierarchical summary receiver operating characteristic (ROC) curve (AUChSROC ) was calculated as an index of accuracy, and pooled estimates of accuracy indices (sensitivity and specificity) were calculated at different cut-off levels. Subgroup and meta-regression analyses were performed to test the robustness of the results. RESULTS: Thirteen studies involving 4416 patients were included. The AUChSROC was 0·89 (95 per cent c.i. 0·86 to 0·92) for clinically significant POPF and 0·88 (0·85 to 0·90) for POPF of any grade. Pooled estimates of sensitivity and specificity were calculated for the different cut-offs: 90-100 units/l (0·96 and 0·54 respectively), 350 units/l (0·91 and 0·84) and 5000 units/l (0·59 and 0·91). Accuracy was independent of the type of operation, type of anastomosis performed and octreotide administration. CONCLUSION: Evaluation of drain amylase content on the first day after surgery is highly accurate in predicting POPF following major pancreatic resection. It may allow early drain removal and institution of an enhanced recovery pathway.

Neoadjuvant chemotherapy and primary-first approach for rectal cancer with synchronous liver metastases.

AIM: Up to a quarter of patients with rectal cancer have synchronous liver metastases at the time of diagnosis. This is a predictor of poor outcome. There are no standardized guidelines for treatment. We reviewed the outcomes of our patients with synchronous rectal liver metastases treated with a curative intent by neoadjuvant chemotherapy with or without chemoradiotherapy followed by resection of the primary tumour and then liver metastases. METHOD: Between 2004 and 2012, patients who presented with rectal cancer and synchronous liver metastasis were treated with curative intent with peri-operative systemic chemotherapy as the first line of treatment. Responders to chemotherapy underwent resection of the primary tumour with or without preoperative chemoradiotherapy followed by hepatic resection. RESULTS: Fifty-three rectal cancer patients with 152 synchronous liver lesions were identified. After a median follow-up of 29.6 months, the median survival was 41.4 months. Overall survival was 59.0% at 3 years and 39.0% at 5 years. CONCLUSION: Rectal resection before hepatic resection combined with neoadjuvant chemotherapy is associated with promising clinical outcome. It allows downstaging of liver lesions and removal of the primary tumour before the progression of further micrometastases. Furthermore, patients who do not respond to chemotherapy can be identified and may avoid major surgical intervention.

Radiofrequency assisted liver resection: analysis of 604 consecutive cases.

BACKGROUND: Intraoperative blood loss is an important factor contributing to morbidity and mortality in liver surgery. To address this we developed a bipolar radiofrequency (RF) device, the Habib 4X, used specifically for hepatic parenchymal transection. The aim of this study was to prospectively assess the peri-operative data using this technique. METHODS: Between 2001 and 2010, 604 consecutive patients underwent liver resections with the RF assisted technique. Clinico-pathological and outcome data were collected and analysed. RESULTS: There were 206 major and 398 minor hepatectomies. Median intraoperative blood loss was 155 (range 0-4300)ml, with a 12.6% rate of transfusion. There were 142 patients (23.5%) with postoperative complications; none had bleeding from the resection margin. Only one patient developed liver failure and the mortality rate was 1.8%. CONCLUSIONS: RF assisted liver resection allows major and minor hepatectomies to be performed with minimal blood loss, low blood transfusion requirements, and reduced mortality and morbidity rates.

Partial nephrectomy and enbloc liver resection using a bipolar radiofrequency device for renal cell carcinoma invading the liver.

A 66-year-old man presented with right- sided abdominal pain. Ultrasound, CT and MRI scans showed a right renal mass arising from the upper pole with direct involvement of the right lobe of the liver. Biopsy confirmed renal cell carcinoma. After Multi Disciplinary Team (MDT) discussion, right partial nephrectomy with enbloc resection of segments VI and VII of the liver was performed with the help of intraoperative ultrasound scan and the Habib 4X bipolar radiofrequency device. Apart from symptomatic collection, which was drained radiologically, the patient made a good recovery. The patient developed recurrence at the resection margin but is in remission following chemotherapy at 12 months.

Survival analysis after pancreatic resection for ampullary and pancreatic head carcinoma: an analysis of clinicopathological factors.

BACKGROUND AND OBJECTIVES: Surgery remains the only curative option for the treatment of pancreatic and ampullary carcinomas. To examine the survival differences between ampullary and pancreatic head carcinomas after pancreaticoduodenectomy. METHODS: A retrospective review of patients with ampullary or pancreatic head adenocarcinoma undergoing curative resection during a 6-year period prior to 2000. RESULTS: A total of 104 patients underwent pancreaticoduodenectomy for pancreatic head and ampullary carcinomas (n = 65 and n = 39, respectively). Histologically, pancreatic cancer was worse, with more lymph node involvement and more positive resection margins and vascular and perineural invasions than found in ampullary carcinoma. The median disease-free and overall survival rates were significantly better for ampullary cancer when compared with pancreatic cancer (17 vs. 9 months [P = 0.001] and 35 vs. 24 months [P = 0.006], respectively). The actuarial 5-year disease-free and overall survival rates were 4.4% and 10.5%, respectively, for pancreatic carcinoma and 27.9% and 31.8%, respectively, for ampullary carcinoma. Multivariate analysis showed that microscopic resection margin involvement (P = 0.02) and involvement of over three nodes (P < 0.001) were significant factors affecting the overall survival for pancreatic and ampullary carcinomas, respectively. CONCLUSIONS: In this study, patients with ampullary carcinoma have a better prognosis and survival than those with pancreatic carcinoma.

Laparoscopic Habib 4X: a bipolar radiofrequency device for bloodless laparoscopic liver resection.

BACKGROUND: In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made laparoscopic hepatic surgery feasible and safe. In spite of this laparoscopic liver resection remains a surgical procedure of great challenge because of the risk of massive bleeding during liver transection and the complicated biliary and vascular anatomy in the liver. A new laparoscopic device is reported here to assist liver resection laparoscopically. METHODS: The laparoscopic Habib 4X is a bipolar radiofrequency device consisting of a 2 x 2 array of needles arranged in a rectangle. It is introduced perpendicularly into the liver, along the intended transection line. It produces coagulative necrosis of the liver parenchyma sealing biliary radicals and blood vessels and enables bloodless transection of the liver parenchyma. RESULTS: Twenty-four Laparoscopic liver resections were performed with LH4X out of a total of 28 attempted resections over 12 months. Pringle manoeuvre was not used in any of the patients. None of the patients required intraoperative transfusion of red cells or blood products. CONCLUSION: Laparoscopic liver resection can be safely performed with laparoscopic Habib 4X with a significantly low risk of intraoperative bleeding or postoperative complications.

Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease.

Evidence is growing in support of the role of stem cells as an attractive alternative in treatment of liver diseases. Recently, we have demonstrated the feasibility and safety of infusing CD34(+) adult stem cells; this was performed on five patients with chronic liver disease. Here, we present the results of long-term follow-up of these patients. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were isolated and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicity and changes in clinical, haematological and biochemical parameters; they were followed up for 12-18 months. All patients tolerated the treatment protocol well without any complications or side effects related to the procedure, also there were no side effects noted on long-term follow-up. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patient's serum bilirubin increased only at 18 months post-infusion. Computed tomography scan and serum alpha-foetoprotein monitoring showed absence of focal lesions. The study indicated that the stem cell product used was safe in the short and over long term, by absence of tumour formation. The investigation also illustrated that the beneficial effect seemed to last for around 12 months. This trial shows that stem cell therapy may have potential as a possible future therapeutic protocol in liver regeneration.

Stem cells as a treatment for chronic liver disease and diabetes.

Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a clinical reality. Cell therapies hold great promise to repair, restore, replace or regenerate affected organs and may perform better than any pharmacological or mechanical device. There is an accumulating body of evidence supporting the contribution of adult stem cells, in particular those of bone marrow origin, to liver and pancreatic islet cell regeneration. In this review, we will focus on the cell therapy for the diseased liver and pancreas by adult haematopoietic stem cells, as well as their possible contribution and application to tissue regeneration. Furthermore, recent progress in the generation, culture and targeted differentiation of human haematopoietic stem cells to hepatic and pancreatic lineages will be discussed. We will also explore the possibility that stem cell technology may lead to the development of clinical modalities for human liver disease and diabetes.

Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.

INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

Adenovirus 5 vector genetically re-targeted by an Affibody molecule with specificity for tumor antigen HER2/neu.

In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance.

A modified radiofrequency-assisted approach to right hemihepatectomy.

AIMS: To evaluate a modified radiofrequency-assisted approach to right hemihepatectomy. METHODS: Following a bilateral subcostal incision and intraoperative ultrasonography, the liver was mobilized in the standard manner, and a cholecystectomy was performed. The portal vein was isolated, encircled, and ligated. After demarcating the liver parenchyma, coagulation necrosis was achieved using a radiofrequency-assisted device along the line demarcated for transecting the liver parenchyma. The actual transection of the liver parenchyma and the right portal vein was done using a surgical scalpel along the radiofrequency-coagulated line. The right hepatic vein was coagulated using the radiofrequency sealer or by stitching in the resection plane. The hepatic artery was not dissected and was sealed together with the bile ducts in the resection plane using the radiofrequency instrument. The hepatic vein was not divided. RESULTS: Between July 2005 and July 2006, a total of 49 liver resections were performed in our unit. Of these, the radiofrequency-assisted technique was used in 33 cases with metastatic disease; 14 of these cases had right hemihepatectomies, including 2 repeat resections. The mean operation time was 180min (range, 120-240min), and the average blood transfusion was 0.14U (range, 0-2U). Postoperatively, there was no morbidity, such as bleeding, infection, or biliary fistula, related to the liver resection technique, and no patients died as a result of surgery. In 8 out of the 14 right hemihepatectomies, a right-sided pleural effusion was observed; 3 of them required evacuation. CONCLUSION: This paper describes a modified radiofrequency-assisted hemihepatectomy, which allows one to obtain control of the portal blood flow going into the resected part of liver. The modified approach appears to be simple and safe.

Short- and-long term results of intraoperative radiofrequency ablation of liver metastases.

BACKGROUND: Surgical resection is the only therapeutic option with curative effect on malignant liver tumours, but in over 70% of cases, this is not a feasible option. A prospective study was performed to assess the short- and long-term effects of intraoperative radiofrequency ablation on unresectable liver metastases. PATIENTS: Between 1997 and 2001, 57 patients (mean age 61.9 years; range 31-83 years) with 297 unresectable liver metastases (colorectal adenocarcinoma, n=38; carcinoid tumour, n=4; malignant melanoma, n=3; other metastases, n=12) underwent intraoperative radiofrequency ablation. RESULTS: No mortality was observed in patients managed solely with radiofrequency ablation. Eight postoperative complications occurred in eight patients (14%). Three occurred when radiofrequency ablation was combined with resection. Of the 33 patients completely ablated, 30 patients are still alive and 21 are disease-free after a median follow-up of 18.1 months (range 2-43). Ten patients underwent more than one intraoperative radiofrequency ablation episode. Overall survival was 72.5% at 1 year and 52.5% at 3 years. Complete ablation and the number of lesions were significant independent prognostic factors for survival, with p<0.001 and p<0.0001, respectively. CONCLUSION: Radiofrequency ablation is a safe and effective option for patients with inoperable liver metastases without extra hepatic disease. Prospective controlled trials comparing the results of different treatments are required to assess which patients will benefit best from this emerging new treatment.

Liver resection in a patient with concomitant thoraco-abdominal and cerebral aneurysms.

BACKGROUND: Surgical resection remains the only curative procedure for liver metastases but even in expert hands it has appreciable morbidity and mortality rates. The presence of a concomitant aortic aneurysm greatly increases these risks. CASE OUTLINE: A 66-year-old woman who was known to have large aneurysms of the thoraco-abdominal aorta and middle cerebral artery presented with colorectal liver metastases. After detailed preoperative assessment, she underwent resection of segments V and VI of the liver. The surgical procedure was uneventful. She made a good initial recovery, but on day 7 she suddenly became hypotensive and died from a cardiorespiratory arrest. Post-mortem examination revealed a ruptured thoracic portion of the thoraco-abdominal aortic aneurysm. CONCLUSION: Despite careful control of perioperative blood pressure and the lack of abdominal complication, intrathoracic aneurysmal rupture on day 7 highlights the risk of major unrelated operations in patients with aneurysmal disease.

Laparoscopic radiofrequency-assisted liver resection.

Laparoscopic liver resection has not yet gained wide acceptance among hepatic surgeons, mainly because of the difficulties encountered in dealing with possible intraoperative bleeding. A new technique of laparoscopic liver resection is presented. A 43-year-old man with a large and symptomatic hemangioma underwent a laparoscopic radiofrequency energy-assisted liver resection. After induction of pneumoperitoneum, four trocars were introduced and intraoperative ultrasonography and coagulative desiccation were performed along a plane of tissue 1 cm away from the edge of the lesion using the Cool-Tip radiofrequency probe and a 500-kHz, radiofrequency generator. The necrosed band of parenchyma then was divided and the specimen removed. The operative time was 300 min with a resection time of 240 min. The intraoperative blood loss was 75 ml. The postoperative course was uneventful and the patient was discharged on postoperative day 6. Laparoscopic radiofrequency-assisted liver resection is feasible, and with greater experience may contribute to the wider use of mini-invasive video-assisted liver surgery.

Mucous cystadenoma of the appendix: is it safe to remove it by a laparoscopic approach?

Mucinous cystadenoma is an uncommon neoplasm of the appendix usually discovered intraoperatively. Its clinical significance lies in the possible rupture and consequent spillage of mucin into the peritoneal cavity, leading to pseudomyxoma peritonei. Even if laparoscopy has been successfully used to perform appendectomy, some concerns exist regarding its use in dealing with mucinous secreting lesions because of possible spillage of mucin during surgery. We report a case of mucous cystadenoma of the appendix, which was successfully removed using a laparoscopic approach. At a 12-month follow-up assessment, the patient was free of disease. We believe that the laparoscopic approach is safe if surgery can be performed without grasping the lesion, and if the specimen is removed through the abdominal wall using a bag. Conversion to laparotomy should be considered if the lesion must be traumatically grasped, or if the tumor clearly extends beyond the appendix.

A novel approach to gallbladder cancer in a Jehovah's Witness.

Transfusion of blood or blood products peri- or postoperatively is often necessary in patients undergoing liver resections for hepatic or biliary tract neoplasms. In Jehovah's Witnesses this inevitably poses a difficult dilemma for clinicians. A 66-year-old female Jehovah's Witness with a T1b gallbladder cancer was referred to our specialist unit for further treatment after having had a routine laparoscopic cholecystectomy in another hospital. Although an abdominal computed tomography scan preoperatively showed a normal liver with no evidence of regional lymph node involvement, histologically the tumor was found in the posterior wall of the gallbladder adherent to the liver bed and had a full thickness involvement of the muscular layer, raising suspicion of a local invasion into the liver bed. The patient, having refused liver resection, was treated with a laparoscopic radiofrequency ablation under intraoperative ultrasound guidance using a newly developed "cooled-tip" needle and a 500-kHz radiofrequency generator. A "zone of necrosis" measuring 3.5 cm in diameter was created in the liver bed and adjacent tissues. The procedure lasted 90 min with no blood loss. Postoperatively, the patient was discharged on the third postoperative day and remained disease free at the 9-month follow-up. Although the follow-up in this case was too short to determine the long-term result of this approach, we believe that this is a single unique case posing a challenging problem to clinicians for which radiofrequency ablation may have a role in offering an alternative to major resections.

Bloodless hepatectomy technique.

BACKGROUND: Surgical resection remains the gold standard in dealing with liver tumours. Blood loss, biliary leak and postoperative liver function are still the main concerns of surgeons operating on the liver, even though different techniques have been developed to allow safer liver resection. A novel concept for liver resection is described using a radiofrequency energy (RF) assisted technique. METHOD: A patient with a large colorectal liver metastasis located in segments VI, VII, VIII underwent a right hepatectomy using this technique. At laparotomy the tumour was staged with intraoperative ultrasonography, and a 'cooled tipped' radiofrequency probe was used to achieve a 'zone of desiccation' in the liver parenchyma 2 cm away from the edge of the tumour. Liver parenchyma was subsequently divided with a surgical scalpel. RESULTS: The resection time was 80 min with a blood loss of 30 ml. The patient was discharged on the ninth postoperative day without complications. DISCUSSION: Liver resection assisted by RF energy is feasible and safe. This technique could offer a new method for 'transfusion-free' resection without the need for sutures, ties, staples, tissue glue or admission to the intensive care unit.

The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines.

It has been suggested the E1B 55 kDa mutant adenovirus dl1520 can selectively kill p53-deficient human tumor cells. In this study, we examined the cytotoxic effect of dl1520 on nine human hepatocellular carcinoma (HCC) cell lines with different p53 genetic and functional status. The results showed that HCC cell lines with deleted or mutant p53 gene and reduced p53 transcriptional activities were more susceptible to dl1520-induced cytolysis. Hep3B (p53-null) and HepG2 (p53-wt) cells were arrested at G2/M phase when cytolysis occurred. Cyclin-dependent kinase inhibitor (CDKI) p21(Waf-1/Cip-1) was downregulated 24 hours after dl1520 infection in HepG2 cells and increased when cytolysis occurred. No p21 expression was detected in Hep3B cells. DNA fragmentation was found in both Hep3B and HepG2 cells after dl1520 infection. Bax expression increased in dl1520-infected HepG2 cells but not in Hep3B cells. Notably, three Bax-like proteins, molecular mass around 40 to 80 kDa, accumulated 48 hours after adenovirus infection in Hep3B cells but not in HepG2 cells. These results suggest that the susceptibility of HCC cells to dl1520-induced cytolysis is related to both p53 genotype and functional status, and is mediated by both cell cycle disturbance and apoptosis.