Open versus laparoscopic liver resection of colorectal metastases: a meta-analysis of matched patient populations.

In recent years, the management of colorectal liver metastases (CRLM) has evolved significantly. Laparoscopic liver resection is increasingly being performed, despite a lack of major randomized controlled trial evidence or widespread international consensus. The objective of this review was to compare the short- and long-term outcomes following open and laparoscopic CRLM resection. A systematic review of comparative matched population studies was performed. Evaluated endpoints included surgical outcomes and survival outcomes. Twelve studies were included in this review, reporting on 3095 patients. R0 (negative margins) rates were higher in the laparoscopic CRLM group (89.3% versus 86.9%). In addition, laparoscopic resection was associated with less blood loss (486 mls versus 648 mls, p ≤ 0.0001*) and reduced blood transfusion rates (6.7% vs. 12.2%, OR 2.13, 95% CI 1.08-4.19, p = 0.03*). Major complication rates were higher in the open CRLM group (12.5% vs. 8.1%, OR 1.74, 95% CI 1.30-2.33, p = 0.03*), as was overall hospital length of stay (median 7 versus 5.5 days, p = 0.001*). Perioperative mortality was similar between both groups, and there was no significance in 5-year overall survival for open or laparoscopic CRLM resection groups (58% and 61% respectively). Laparoscopic CRLM resection is associated with less blood loss, lower transfusion rates, major complications, and overall hospital length of stay with comparable oncological outcome.

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

BACKGROUND: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. OBJECTIVES: To determine the association between mortality and the development of early IPN. METHODS: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. RESULTS: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Prevalence and Sonographic Detection of Gallbladder Polyps in a Western European Population.

BACKGROUND: Gallbladder cancer is rare but associated with significant morbidity and mortality necessitating the early identification of premalignant and malignant lesions to improve overall prognosis. Despite limited evidence regarding the effectiveness of transabdominal ultrasound (US) in the detection of gallbladder polyps, it plays a key role in current European guidelines. The aim of this study was to investigate gallbladder polyp prevalence in a western European population and assess the diagnostic accuracy of transabdominal US. METHODS: Data from patients who underwent cholecystectomy for US detected gallbladder polypoid lesions at four hospitals in Ireland and the United Kingdom between 2010 and 2018 were retrospectively collected. Patient demographics, ultrasonographic, and histopathologic findings were analyzed. RESULTS: A total of 134 patients underwent cholecystectomy for US-detected gallbladder polyps. After histopathologic examination, pseudopolyps were found in 75 (56%) specimens with dysplastic or malignant polyps seen in only six (4.5%) specimens. Mean size for neoplastic polyps was 33 mm. The positive predictive value for US in detecting neoplastic polyps in this study was 4.5%, which is significantly lower than the 10%-15% reported previously. CONCLUSIONS: Although the prevalence of neoplastic polyps in this study is higher than in the previous literature, the distribution of pseudopolyps and true polyps is as expected. With all malignant polyps being >10 mm in diameter, these findings support the current size thresholds stated in European guidelines. The poor diagnostic accuracy of US demonstrated may have led to significant number of patients undergoing unnecessary surgical intervention, further supporting the argument for improved strategies for the investigation of gallbladder polyps.

Outcomes of Patients Treated With Upfront Cholecystostomy for Severe Acute Cholecystitis.

INTRODUCTION: Percutaneous cholecystostomy tube (PCT) placement is a treatment method for acute cholecystitis, both in adult patients unsuitable for surgery and those failing to improve with conservative management. The purpose of this study was to assess the outcomes of patients undergoing cholecystostomy. MATERIALS AND METHODS: A review of consecutive patients who underwent PCT insertion over a 10-year period was performed. Outcomes assessed included cholecystostomy dwell time, tubogram requirement, cholecystostomy reinsertion, cholecystectomy, bile leaks, and mortality. RESULTS: One hundred eight patients (77 male individuals, 31 female individuals) were included. The mean age was 70 years (range: 29 to 93 y). A total of 89 transhepatic and 19 transperitoneal PCTs were inserted. Fifty-nine patients (55%) had a subsequent tubogram to assess cystic duct patency or catheter position. Mean catheter dwell time was 17 days (range: 1 to 154 d). Eleven (10%) required PCT reinsertion. Time to reinsertion ranged from 2 to 163 days (mean=38 d). Fifty-three patients (50%) had no further biliary intervention after removal of the cholecystostomy catheter. One patient required subsequent drainage of a hepatic abscess, and another developed a biloma. Thirty-two patients (30%) underwent cholecystectomy (66% laparoscopic, 34% open). Thirty-day mortality after PCT insertion was 8.3%. Twenty patients (19%) died of non-cholecystostomy-related illness during the 10-year follow-up period. CONCLUSIONS: Cholecystostomy is an important treatment method of acute cholecystitis as a bridge to cholecystectomy or as an alternative definitive treatment option in those unsuitable for surgery. A tubogram is not always necessary before tube removal. Cholecystostomy tubes can be removed safely with little risk of bile leak if patients are clinically well, and clean-appearing bile is draining.

Selective Necrosectomy for Infected Pancreatic Necrosis.

BACKGROUND: Until recently, a diagnosis of infected pancreatic necrosis (IPN) warranted necrosectomy, which was associated with high morbidity and mortality rates greater than 20%. Preoperative percutaneous drainage delayed the need for necrosectomy with improved outcomes. METHODS: In 2008, this institution changed its approach to the management of such cases opting instead for percutaneous drainage with selective deferred necrosectomy. A total of 38 consecutive patients with IPN from January 2008 to December 2014 were included. RESULTS: All 38 underwent percutaneous radiological drainage, and selective necrosectomy was performed on 15 where the infected necrosis did not completely resolve. Twenty-three patients did not require surgery and were managed with pancreatic drain insertion, optimal nutritional support and critical care interventions. Median peak Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores were 10 (range 0-18) and 3 (range 0-10) prior to radiological intervention. Overall mortality was 5% (n = 2). CONCLUSION: This study demonstrates that radiological-guided drainage of infected pancreatic collections can, in most cases, prove curative and, if not, facilitates delayed surgical intervention with improved outcomes.

Osteoclastic-Type Giant Cell Tumours of the Pancreas: A Homogenous Series of Rare Tumours Diagnosed by Endoscopic Ultrasound.

BACKGROUND: Giant cell tumors (GCT) of the pancreas are a rare form of pancreatic cancer. Although data are limited, clinical outcomes appear to depend largely on histological subtype with osteoclastic tumors carrying a better prognosis. We report on a homogenous series of patients with osteoclastic-type GCTs of the pancreas presenting to a national pancreatico-biliary gastrointestinal oncology center. METHODS: Patients underwent endoscopic, radiological and histopathological assessments. Data were collected in relation to consecutive patients presenting with osteoclastic-type tumors of the pancreas and analyzed with survival as a primary end point. RESULTS: Four patients were treated over a 4-year period. Median age was 77 years with equal gender distribution. Median tumor size was 42 mm. Histology was osteoclast-type giant cells in all 4 patients. Two patients underwent surgery with curative intent. Median overall survival was 13.1 months. CONCLUSION: This is the largest reported series of osteoclast-type histology in GCTs of the pancreas.

Extension of hepatic necrosis secondary to current arcing to surgical clips: a potential complication of radiofrequency ablation.

The authors present a case report of a 67-year-old woman who underwent radiofrequency ablation of recurrent hepatic metastases. She was managed 2 years previously with a right hemi-hepatectomy. Subsequent to RF ablation she developed hepatic necrosis extending in a linear fashion to two of the metallic surgical clips at the free edge of the liver, consistent with current arcing.

Changes in hepatic immunoregulatory cytokines in patients with metastatic colorectal carcinoma: implications for hepatic anti-tumour immunity.

The hepatic immunological environment, dominated by NK and NKR(+) T cells, seems specialised to respond to malignant challenge. Ineffective immune responses to malignancy are likely determined by factors including alterations in the local cytokine profile. This study examines the cytokine milieu of normal and tumour-bearing liver, quantifying pro-/anti-inflammatory cytokines using modified ELISAs and real-time quantitative PCR. Cytokine protein was localised using immunohistochemistry. We demonstrate an active cytokine environment in normal liver, with high levels of inflammatory and regulatory cytokines. Inflammatory IFN-gamma was increased in tumour-bearing liver (p<0.0001). However, a much greater increase in anti-inflammatory IL-10, produced by non-parenchymal cells (p<0.0005), resulted in a reduced IFN-gamma:IL-10 ratio in tumour-bearing liver (p<0.02). In contrast, immunosuppressive TGF-beta and IL-13 were significantly downregulated (p<0.02). Furthermore, IL-2 was not increased and IL-15 was reduced (p<0.02). The IFN-gamma inducing cytokine, IL-18 was increased in tumour-bearing liver (p<0.02), while pro-inflammatory TNF-alpha was suppressed (p<0.05). These results suggest that, whilst there is a significant inflammatory immune response in tumour-bearing liver, evidenced by increased levels of IFN-gamma, disproportionate increase in IL-10 may be a key factor in facilitating tumour progression. Therapies aimed at antagonising IL-10-mediated immunosuppression may prove a useful strategy in the future treatment of metastatic disease.

Long-term quality of life following pancreaticoduodenectomy.

BACKGROUND/AIMS: This study examined long-term quality of life in an unselected consecutive cohort of patients undergoing pancreaticoduodenectomy, both Whipple and total, for benign and malignant disease. METHODOLOGY: Forty consecutive patients who underwent pancreaticoduodenectomy over a nine-year period formed the study group. The control group consisted of 58 age- and sex-matched patients undergoing open cholecystectomy during the same period. Quality of Life was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 (core cancer module) and QLQ-PAN26 (pancreatic cancer module) questionnaires at a median of 42 months postoperatively. RESULTS: The Global Health Status of the study and control groups was similar, but significant differences were noted in certain individual scales. The benign group reported greater social and financial difficulties, and symptoms consistent with impaired exocrine function. The malignant group reported difficulties with daily physical and role functioning, concern for future health and individual symptoms such as fatigue, muscle weakness, and inability to gain weight. CONCLUSIONS: This study demonstrates that the overall quality of life of patients who underwent pancreaticoduodenectomy compared favorably with that of a control group. Significant differences did exist in some individual scales, in both the benign and malignant sub-groups, suggestive of exocrine insufficiency.

Nitric oxide in early ischaemia reperfusion injury during human orthotopic liver transplantation.

BACKGROUND: Altered nitric oxide (NO) metabolism has been shown to contribute to ischemia-reperfusion (IR) injury in animal models. However, similar studies have not been performed in human liver transplantation (LT). In this study, we examined nitrate, nitrite, and nitrosothiols (NOx), NO synthases (endothelial [constitutive] nitric oxide synthase [eNOS] and inducible nitric oxide synthase [iNOS]), and nitrotyrosine in early IR injury after human LT. METHODS: Paired biopsies were obtained from nine donor livers before cold ischemia (retrieval biopsy) and after reimplantation (reperfusion biopsy). Sections were graded for reperfusion injury using the Suzuki score. NO was detected by chemiluminescence after reduction of NOx. Expression of eNOS and iNOS was by Western blot and reverse transcriptase polymerase chain reaction and peroxynitrite by immunodetection of 3-nitrotyrosine. RESULTS: Reperfusion biopsies showed histologic evidence of injury (median Suzuki score: retrieval 2, reperfusion 6, P=0.008) and neutrophil infiltration. NOx was reduced after reperfusion from 5.41 microM/100 mg (median, range 2.17-13.39 microM) to 3.51 microM (1.45-5.66 microM, P=0.05). eNOS protein was reduced after reperfusion from 0.6 units (median, range 0.45-1 unit) in retrieval biopsies to 0.39 units in reperfusion biopsies (range 0.2-0.79 units, P=0.007). There was no change in eNOS or iNOS mRNA expression or iNOS protein. Western blotting showed increased nitrotyrosine formation after reperfusion, median 0.42 (range 0.16-0.87) units in retrieval biopsies and 0.68 (0.29-1.06) units in reperfusion samples (P=0.007) and localized to periportal regions. CONCLUSIONS: iNOS protein may not contribute to early reperfusion injury during human LT. However, reduced NO bioavailability caused by reduced eNOS may contribute significantly to damage at this time point.

Interleukin 12 (IL-12) is increased in tumour bearing human liver and expands CD8(+) and CD56(+) T cells in vitro but not in vivo.

Human liver is enriched with CD8(+)T- and CD3(+)CD56(+) natural T (NT)-lymphocytes, important anti-tumour effectors, similar to murine NKTs. IL-12 promotes anti-tumour functions of NKTs. We quantified IL-12 and CD56(+)/CD8(+)T lymphocytes in normal and tumour bearing liver. We also examined the effect of IL-12 on the expansion/activation of peripheral blood cells in vitro. IL-12 was detected in normal (n=13, median 2032 pg/100 mg protein) and increased in tumour bearing liver (n=9, 3678 pg, p< 0.01). Infiltrating monocytes appear to be the principal producers. Culture with IL-12 selectively expanded CD8(+)T and CD3(+)CD56(+)NT cells and polarised their cytokine responses to Th1-type. However, there was no in vivo expansion of these cells in tumour bearing liver. Changes observed in culture required addition of IL-2. We therefore quantified IL-2 in hepatic tissue. IL-2 was detected in normal liver (median 4700 pg/100 mg protein). Surprisingly, there was no increase in tumour-infiltrated liver (4910 pg). The presence of IL-12 may create an environment in healthy liver that promotes the accumulation of CD8(+)T and CD56(+)NT cells. Therefore, the development of metastases in the presence of high levels of IL-12 may be due to an insufficient IL-12 response. Alternatively, lack of IL-2 rather than a defect in IL-12, may be responsible for insufficient expansion/activation of tumour specific cytotoxic T lymphocytes.

Cystic duct remnant and the 'post-cholecystectomy syndrome'.

Post-cholecystectomy syndrome refers to a wide spectrum of conditions that pose a challenging diagnostic dilemma. Cystic duct remnant, defined as a residual duct greater than 1 cm in length, may, in the presence of stones, cause post-cholecystectomy syndrome. In this report, 4 patients with post-cholecystectomy syndrome due to cystic duct remnant are described. All underwent laparoscopic cholecystectomy and one was converted to open. The patients presented with pain 10 months to 9 years post-cholecystectomy and investigations demonstrated cystic duct remnant. All patients underwent successful resection with resolution of symptoms. In this era of laparoscopic surgery, where surgery favors a long cystic duct remnant, we should be aware of cystic duct stones as a possible cause of postcholecystectomy syndrome. This report highlights magnetic resonance cholangiopancreatography as the optimal method for evaluating the biliary tract in these cases.

Localization of T and B lymphocytes in histologically normal adult human donor liver.

BACKGROUND/AIMS: Donor liver suitable for successful transplantation often has one or more of a range of mild abnormalities including inflammation. Passenger leukocytes documented in donor liver are thought to result from inflammatory stimuli in response to ischemic, drug or alcohol related damage. The aim was to identify donor livers, which were free of any evidence of damage, and to determine if, and where, leukocytes were present in these pristine livers. METHODOLOGY: Eight of eighteen donor livers, examined by hematoxylin and eosin staining, were found to be free of any evidence of pathological damage. Sections from these livers were stained with antibodies against CD3 (T cell marker), CD20 (B cell marker) and CD45 (common leukocyte antigen). RESULTS: Each of these livers were found to have significant numbers of T lymphocytes, located mainly in the portal tracts but also scattered throughout the parenchyma. A similar distribution of B cells was detected but at much lower levels. CONCLUSIONS: The presence of lymphocytes in the human liver is usually considered a hallmark of pathology. The demonstration of significant lymphocyte populations in pristine liver, particularly in the parenchyma, supports the hypothesis that the human liver harbors tissue-resident lymphocytes.

Selective reduction of natural killer cells and T cells expressing inhibitory receptors for MHC class I in the livers of patients with hepatic malignancy.

Natural killer (NK) and CD56(+) T cells are thought to play a central role in antitumour immunity. Their cytolytic activities are controlled by a variety of receptors including CD94 and killer immunoglobulin-like receptors (KIR), which bind to major histocompatibility complex (MHC) class I molecules on target cells and mediate cell activation or inhibition. We have examined the numbers, phenotypes and antitumour cytotoxic functions of hepatic NK and CD56(+) T cells isolated from 22 patients with hepatic malignancy and 19 healthy donors. Flow cytometry revealed that NK cell numbers were increased among hepatic mononuclear cells in malignancy compared to histologically normal livers (mean: 38% vs 27%; P=0.03), but CD56(+) T cell numbers were not (28% vs 27%). NK cells and CD56(+) T cells from tumour-bearing livers exhibited lymphokine-activated killing of K562 targets and T cell receptor-mediated lysis of P815 cells. The expression of CD94 and the KIR isotypes CD158a, CD158b and KIR3DL1 by CD56(+) T cells and NK cells was significantly and consistently reduced in tumour-bearing livers compared to healthy livers ( P<0.05 in all cases). Simultaneous ligation of CD158a, CD158b and KIR3DL1 caused an overall partial inhibition of CD56(+) T cell cytotoxic activity, suggesting that the observed reductions in KIR(+) cell numbers in malignancy are likely to lead to enhanced cytotoxicity. Our results suggest that, while hepatic CD56(+) T cells are not expanded in malignancy, downregulation of KIR and CD94 expression may be a mechanism by which the hepatic immune system can be activated to facilitate tumour rejection.

IAP Guidelines for the Surgical Management of Acute Pancreatitis.

During 2002 the International Association of Pancreatology developed evidenced-based guidelines on the surgical management of acute pancreatitis. There were 11 guidelines, 10 of which were recommendations grade B and one (the second) grade A. (1) Mild acute pancreatitis is not an indication for pancreatic surgery. (2) The use of prophylactic broad-spectrum antibiotics reduces infection rates in computed tomography-proven necrotizing pancreatitis but may not improve survival. (3) Fine-needle aspiration for bacteriology should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome. (4) Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention including surgery and radiological drainage. (5) Patients with sterile pancreatic necrosis (with negative fine-needle aspiration for bacteriology) should be managed conservatively and only undergo intervention in selected cases. (6) Early surgery within 14 days after onset of the disease is not recommended in patients with necrotizing pancreatitis unless there are specific indications. (7) Surgical and other forms of interventional management should favor an organ-preserving approach, which involves debridement or necrosectomy combined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate. (8) Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis. (9) In mild gallstone-associated acute pancreatitis, cholecystectomy should be performed as soon as the patient has recovered and ideally during the same hospital admission. (10) In severe gallstone-associated acute pancreatitis, cholecystectomy should be delayed until there is sufficient resolution of the inflammatory response and clinical recovery. (11) Endoscopic sphincterotomy is an alternative to cholecystectomy in those who are not fit to undergo surgery in order to lower the risk of recurrence of gallstone-associated acute pancreatitis. There is however a theoretical risk of introducing infection into sterile pancreatic necrosis. These guidelines should now form the basis for audit studies in order to determine the quality of patient care delivery.

Intraperitoneal pethidine versus intramuscular pethidine for the relief of pain after laparoscopic cholecystectomy: randomized trial.

Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure. We undertook a randomized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy. A series of 100 consecutive American Society of Anesthesiologists (ASA) I or II patients were randomly assigned to intramuscular pethidine (54 patients) or intraperitoneal pethidine (46 patients). Each was combined with intraperitoneal bupivacaine. The primary endpoints were the pain and nausea scores at intervals after operation. All recruited patients completed the study. Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined (pain at rest at 4 hours: 1.6 +/- 0.8 vs. 2.4 +/- 0.9 cm; p < 0.001; pain upon movement at 4 hours: 2.1 +/- 0.9 vs. 3.1 +/- 1.2 cm; p < 0.001). The total dose of pethidine administered via patient-controlled analgesia (PCA) during the first 24 hours after surgery was also significantly lower in this group (total dose 50.9 +/- 3.9 vs. 55.9 +/- 4.4 mg; p < 0.001). There were no significant differences in the respiratory rate at any of the time periods. Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. This was achieved at the expense of increased nausea but no significant increase in vomiting. The accessibility of this route of analgesia administration has implications for patients undergoing laparoscopic procedures, particularly with the recent trend toward increased use of ambulatory techniques.

Decrease in hepatic CD56(+) T cells and V alpha 24(+) natural killer T cells in chronic hepatitis C viral infection.

BACKGROUND/AIMS: The intrahepatic immune system is likely to play a key role in determining the outcome of hepatitis C virus (HCV) infection. The hepatic lymphocyte repertoire is characterised by high CD8/CD4 T cell ratios and large numbers of gamma delta T cells, natural killer (NK) cells, NK T cells and NK receptor-positive T cells. It is not known which of these populations contribute to immunity against HCV or immune pathology. METHODS: To explore the relative contributions of lymphocyte subpopulations, we have compared the intrahepatic lymphocyte repertoires and cytokine expression in 13 patients with mild chronic hepatitis C infection, 14 with end-stage hepatitis C cirrhosis and five histologically normal livers by flow cytometry and immunohistochemistry. RESULTS: CD4(+) T cells bearing alpha beta T cell receptors (TCR) were significantly expanded in livers with chronic HCV infection while CD56(+) alpha beta T cells and V alpha 24 TCR-positive T cells were significantly depleted. Expanded CD4(+)T cells were predominantly Th1 cells, producing interferon-gamma but not interleukin-4. CONCLUSIONS: Failure to resolve HCV infection may be due to deficient innate and/or memory immune responses, while Th1 cells may mediate immune pathology.