Evidence-Based Approach to the Surgical Management of Acute Pancreatitis.

Background Acute pancreatitis is a significant challenge to health services. Remarkable progress has been made in the last decade in optimizing its management. Methods This review is a comprehensive assessment of 7 guidelines employed in current clinical practice with an appraisal of the underlying evidence, including 15 meta-analyses/systematic reviews, 16 randomized controlled trials, and 31 cohort studies. Results Key tenets of early management of acute pancreatitis include severity stratification based on the degree of organ failure and early goal-directed fluid resuscitation. Rigorous determination of etiology reduces the risk of recurrence. Early enteral nutrition and consideration of epidural analgesia have been pioneered in recent years with promising results. Indications for invasive intervention are becoming increasingly refined. The definitive indications for endoscopic retrograde cholangiopancreatography in acute pancreatitis are associated with cholangitis and common bile duct obstruction. The role of open surgical necrosectomy has diminished with the development of a minimally invasive step-up necrosectomy protocol. Increasing use of endoscopic ultrasound-guided intervention in the management of pancreatic necrosis has helped reduce pancreatic fistula rates and hospital stay. Conclusion The optimal approach to surgical management of complicated pancreatitis depends on patient physiology and disease anatomy, in addition to the available resources and expertise. This is best achieved with a multidisciplinary approach. This review provides a distillation of the recommendations of clinical guidelines and critical discussion of the evidence that informs them and presents an algorithmic approach to key areas of patient management.

An Evaluation of the Evidence Guiding Adult Midline Ventral Hernia Repair.

Purpose: Several guidelines have been published in recent years to guide the clinician in ventral hernia repair. This review distils this advice, critically assesses their evidence base, and proposes avenues for future study. Methods: A PUBMED search identified four guidelines addressing midline ventral hernia repair published by major surgical societies between 2016 and 2020. The studies used to inform the advice have been critically appraised, including 20 systematic reviews/meta-analyses, 10 randomized controlled trials, 32 cohort studies, and 14 case series. Results: Despite a lack of randomized controlled trials, case heterogeneity, and variation in outcome reporting, key themes have emerged. Preoperative computed tomography scan assesses defect size, loss of domain, and the likely need for component separation. Prehabilitation, frailty assessment, and risk stratification are beneficial in complex cases. Minimally invasive component separation techniques, Botox injection, and progressive pneumoperitoneum represent novel techniques to promote closure of large fascial defects. Rives-Stoppa sublay mesh repair has become the "gold" standard for open and minimally invasive repairs. Laparoscopic repair promotes early return to functional status. The enhanced-view totally extraperitoneal approach facilitates laparoscopic sublay mesh placement, avoiding mesh contact with viscera. Robotic techniques continue to evolve, although the evidence at present remains immature. Synthetic mesh is recommended for use in clean and clean-contaminated cases. However, optimism regarding the use of biologic and biosynthetic meshes in the contaminated setting has waned. Conclusions: Surgical techniques in ventral hernia repair have advanced in recent years. High-quality data has struggled to keep pace; rigorous clinical trials are required to support the surgical innovation.

Open Appendicectomy under Spinal Anesthesia-A Valuable Alternative during COVID-19.

Introduction Concerns relating to coronavirus disease 2019 (COVID-19) and general anesthesia (GA) prompted our department to consider that open appendicectomy under spinal anesthesia (SA) avoids aerosolization from intubation and laparoscopy. While common in developing nations, it is unusual in the United Kingdom. We present the first United Kingdom case series and discuss its potential role during and after this pandemic. Methods We prospectively studied patients with appendicitis at a British district general hospital who were unsuitable for conservative management and consequently underwent open appendicectomy under SA. We also reviewed patient satisfaction after 30 days. This ran for 5 weeks from March 25th, 2020 until the surgical department reverted to the laparoscopic appendicectomy as the standard of care. Main outcomes were 30-day complication rates and patient satisfaction. Results None of the included seven patients were COVID positive. The majority (four-sevenths) had complicated appendicitis. There were no major adverse (Clavien-Dindo grade III to V) postoperative events. Two patients suffered minor postoperative complications. Two experienced intraoperative pain. Mean operative time was 44 minutes. Median length of stay and return to activity was 1 and 14 days, respectively. Although four stated preference in hindsight for GA, the majority (five-sevenths) were satisfied with the operative experience under SA. Discussion Although contraindications, risk of pain, and specific complications may be limiting, our series demonstrates open appendicectomy under SA to be safe and feasible in the United Kingdom. The technique could be a valuable contingency for COVID-suspected cases and patients with high-risk respiratory disease.

Ruptured ovarian dermoid cyst - an unusual cause for peritonitis in pregnancy: a case report.

Computed tomography scanning could be safely used in later pregnancy to aid diagnosis and target management of the acute abdomen.

Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury.

AIM: To investigate the hepatic microcirculatory changes due to Haemoxygenase (HO), effect of HO inhibition on remote ischemic preconditioning (RIPC) and modulation of CINC. METHODS: Eight groups of animals were studied - Sham, ischemia reperfusion injury (IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion, RIPC (remote ischemic preconditioning) + IRI group, remote ischemic preconditioning in sham (RIPC + Sham), PDTC + IR (Pyridodithiocarbamate, HO donor), ZnPP + RIPC + IRI (Zinc protoporphyrin prior to preconditioning), IR-24 (45 min of ischemia followed by 24 h of reperfusion), RIPC + IR-24 (preconditioning prior to IR). After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS: Velocity of flow (160.83 ± 12.24 µm/s), sinusoidal flow (8.42 ± 1.19) and sinusoidal perfusion index (42.12 ± 7.28) in hepatic IR were lower (P < 0.05) in comparison to RIPC and PDTC (HO inducer). RIPC increased velocity of flow (328.04 ± 19.13 µm/s), sinusoidal flow (17.75 ± 2.59) and the sinusoidal perfusion index (67.28 ± 1.82) (P < 0.05). PDTC (HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity (300.88 ± 22.109 µm/s), sinusoidal flow (17.66 ± 3.71) and sinusoidal perfusion (82.33 ± 3.5) to near sham levels. ZnPP (HO inhibition) reduced velocity of flow of RBC in the RIPC group (170.74 ± 13.43 µm/s and sinusoidal flow in the RIPC group (9.46 ± 1.34). ZnPP in RIPC (60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules (769.05 ± 87.48) and sinusoids (97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules (219.66 ± 93.79) and sinusoids (25.69 ± 9.08) (P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules (89.58 ± 58.32) and sinusoids (17.98 ± 11.01) (P < 0.05) reproducing the effects of RIPC. ZnPP (HO inhibition) increased venular (589.04 ± 144.36) and sinusoidal neutrophil adhesion in preconditioned animals (121.39 ± 30.65) (P < 0.05). IR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI (80.83 ± 13.03), RIPC + IR (17.35 ± 2.47), and PTDC + IR (11.66 ± 1.17) reduced hepatocellular death. ZnPP + RIPC + IR (41.33 ± 3.07) significantly increased hepatocellular death (P < 0.05 PTDC/RIPC vs ZnPP and IR). The CINC cytokine levels in sham (101.32 ± 6.42). RIPC + sham (412.18 ± 65.24) as compared to sham (P < 0.05). CINC levels in hepatic IR were (644.08 ± 181.24). PDTC and RIPC CINC levels were significantly lower than hepatic IR (P < 0.05). HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels (521.81 ± 74.9) (P < 0.05). The serum CINC levels were high in the late phase of hepatic IR (15306 ± 1222.04). RIPC reduced CINC levels in the late phase of IR (467.46 ± 26.06), P < 0.05. CONCLUSION: RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR.

Diaphragmatic hernia after liver transplantation in children: case series and review of the literature.

A diaphragmatic hernia (DH) is a rare complication of pediatric liver transplantation (LT), with multiple factors implicated in the pathophysiology. It is a potentially life-threatening condition in the absence of early recognition and surgical treatment. A DH after LT has been reported in 16 patients in 7 case series. We report 10 cases from our institution and review the published literature to understand the underlying pathophysiology. The study sample included all children (<18 years of age) who underwent LT from October 1989 to August 2013 at our center and subsequently presented with a DH. Among 4433 LT procedures performed in this time period, 1032 were for children. Ten DH cases were recognized, and risk factors were assessed. The mean age at diagnosis was 4.9 years, all patients with a DH received left lateral segment split grafts, and the mean graft weight was 248 ± 41 g with a mean graft-to-recipient body weight ratio (GBWR) of 3% ± 1.22% (range = 1.7%-5.0%). The mean cold ischemia time was 510.7 ± 307.6 minutes (range = 60-900 minutes). Six patients had a primary abdominal muscle closure, 3 had a temporary Silastic mesh closure, and 1 had a skin closure only. Postoperative ascites and pleural effusion did not appear to be significant risk factors. All 10 children presented with a right posterolateral DH, with 1 also having a left DH. The small bowel was herniated in the majority. All patients underwent prompt surgical intervention without complications. An early age, a split graft, and a high GBWR may be risk factors for a DH. A high index of suspicion and prompt surgical intervention minimize complications.

The hepatic soluble guanylyl cyclase-cyclic guanosine monophosphate pathway mediates the protection of remote ischemic preconditioning on the microcirculation in liver ischemia-reperfusion injury.

BACKGROUND: Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-cGMP) pathway. The present study aimed to assess the role of hepatic sGC-cGMP in lower limb RIPC-induced protection against liver IR injury. METHODS: Mice were allocated to 4 groups: 1.Sham; 2.IR: 40 min of lobar hepatic ischemia and 2 hr reperfusion; 3.RIPC+IR: 6 cycles of 4x4 min IR of the lower limb followed by IR group procedure; (4) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ)+RIPC+IR: ODQ (sGC inhibitor) was administered followed by RIPC+IR group procedure. Hepatic microcirculatory blood flow (MBF) was measured throughout the experiment. Plasma transaminases, hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic cGMP levels were measured in groups 1-3 in addition to an RIPC alone group. RESULTS: Compared to liver IR alone, RIPC+IR increased hepatic MBF during liver reperfusion (P<0.05), and reduced plasma transaminases (P<0.05) and ultrastructural markers of injury. In contrast compared to RIPC+IR, ODQ+RIPC+IR decreased hepatic MBF (P<0.05) and ultrastructural markers of injury. However, plasma transaminases were not significantly different in the ODQ+RIPC+IR compared to the RIPC+IR group. Hepatic cGMP levels were significantly elevated in the RIPC compared to sham group. CONCLUSIONS: The hepatic sGC-cGMP pathway is required for mediating the protective effects of lower limb RIPC on hepatic MBF in liver IR injury.

Modulation of microcirculatory changes in the late phase of hepatic ischaemia-reperfusion injury by remote ischaemic preconditioning.

BACKGROUND: Remote ischaemic preconditioning (RIPC) is a novel method of protecting the liver from ischaemia-reperfusion (I-R) injury. Protective effects in the early phase (4-6 h) have been demonstrated, but no studies have focused on the late phase (24 h) of hepatic I-R. This study analysed events in the late phase of I-R following RIPC and focused on the microcirculation, inflammatory cascade and the role of cytokine-induced neutrophil chemoattractant-1 (CINC-1). METHODS: A standard animal model was used. Remote preconditioning prior to I-R was induced by intermittent limb ischaemia. Ischaemia was induced in the left and median lobes of the liver (70%). The animals were recovered after 45 min of liver ischaemia. At 24 h, the animals were re-evaluated under anaesthesia. Hepatic microcirculation, sinusoidal leukocyte adherence and hepatocellular death were assessed by intravital microscopy, hepatocellular injury by standard biochemistry and serum CINC-1 by enzyme-linked immunosorbent assay (ELISA). RESULTS: At 24 h post I-R, RIPC was found to have improved sinusoidal flow by increasing the sinusoidal diameter. There was no effect of preconditioning on the velocity of red blood cells, by contrast with the early phase of hepatic I-R. Remote ischaemic preconditioning significantly reduced hepatocellular injury, neutrophil-induced endothelial injury and serum CINC-1 levels. CONCLUSIONS: Remote ischaemic preconditioning is amenable to translation into clinical practice and may improve outcomes in liver resection surgery and transplantation.

Nitric oxide is an essential mediator of the protective effects of remote ischaemic preconditioning in a mouse model of liver ischaemia/reperfusion injury.

NO (nitric oxide) may protect the liver from IR (ischaemia/reperfusion) injury. RIPC (remote ischaemic preconditioning) also protects against liver IR injury; however, the molecular mediator(s) of RIPC are currently unknown. The aim of the present study was to assess the role of NO in hindlimb RIPC-induced protection against liver IR injury. Mice were allocated to the following groups: sham group; RIPC group (six cycles of 4×4 min IR of hindlimb); IR group [40 min lobar (70%) hepatic ischaemia and 2-h reperfusion]; RIPC+IR group (RIPC followed by IR group procedures); and C-PTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt]+RIPC+IR group [C-PTIO (a direct NO scavenger) was administered, followed by the RIPC+IR group procedure]. Hepatic MBF (microcirculatory blood flow) was measured throughout the experiment. Circulating NOx (nitrite and nitrate) levels, plasma liver transaminases, hepatic histopathological and TEM (transmission electron microscopy) studies were performed at the end of the experiment. NOx concentrations were significantly elevated (P<0.05) in the RIPC and RIPC+IR groups. Compared with liver IR alone, RIPC+IR preserved hepatic MBF during liver reperfusion (P<0.05). In contrast, C-PTIO+RIPC+IR reduced MBF compared with RIPC+IR (P<0.05). RIPC+IR reduced plasma transaminases (P<0.05), and histopathological and ultrastructural features of injury compared with IR alone. The protective effects of RIPC+IR in reducing liver IR injury were abrogated in the group that received antecedent C-PTIO (C-PTIO+RIPC+IR). In conclusion, NO is an essential mediator of the protection afforded by hindlimb RIPC against liver IR injury. The mechanisms underlying this protection involve preservation of the sinusoidal structure and maintenance of blood flow through the hepatic microcirculation.

Effect of remote ischemic preconditioning on liver ischemia/reperfusion injury using a new mouse model.

Ischemic preconditioning of remote organs (RIPC) reduces liver ischemia/reperfusion (IR) injury in the rabbit and rat. Mice are the only species available with a large number of transgenic strains. This study describes development and validation of a mouse model of hindlimb RIPC that attenuates liver IR injury. Mice were allocated to 4 groups: (1) Sham surgery; (2) RIPC: 6 cycles of 4 × 4 minutes ischemia/reperfusion of hindlimb; (3) IR: 40 minutes lobar (70%) hepatic ischemia and 2 hours reperfusion; (4) RIPC+IR: RIPC followed by IR group procedures. Plasma liver aminotransferases and hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic microcirculatory blood flow was measured throughout the experiment. Postoperative complications and animal survival were evaluated. Hindlimb RIPC using a tourniquet resulted in limb paralysis. Hindlimb RIPC using direct clamping of the femoral vessels showed no side effects. Compared to liver IR alone, RIPC+IR reduced plasma aminotransferases (P < 0.05) and histopathological and ultrastructural features of injury. Hepatic microcirculatory blood flow was preserved in the RIPC+IR compared to IR group (P < 0.05). There was no mortality in any of the groups. By demonstrating a consistent improvement in these features of liver IR injury with antecedent hindlimb RIPC and by minimizing experimental confounding variables, we validated this mouse model. In conclusion, we describe a validated mouse model of hindlimb RIPC that reduces liver IR injury. With the availability of transgenic mice strains, this model should prove useful in unraveling the mechanisms of protection of hindlimb RIPC.

Attenuation of warm ischemia-reperfusion injury in the liver by bucillamine through decreased neutrophil activation and Bax/Bcl-2 modulation.

BACKGROUND AND AIM: Liver transplantation and resection surgery involve a period of ischemia and reperfusion to the liver, which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low molecular weight thiol antioxidant that is capable of rapidly entering cells. We hypothesized that bucillamine acts by replenishing glutathione levels, thus reducing neutrophil activation, modulating Bax/Bcl-2 expression, and subsequently, attenuating the effects of warm ischemia-reperfusion injury (IRI) in the liver. METHODS: The effect of bucillamine was studied in a rat model of liver IRI with 45 min of partial (70%) liver ischemia and 3 h of reperfusion. Liver injury was assessed by measuring serum transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and liver histology. Oxidative stress was quantified by measuring F(2) isoprostane and glutathione levels. Leukocyte adhesion was assessed by intravital microscopy, and inflammatory cytokine response was assessed by measuring serum cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels. Bax and Bcl-2 expression was measured by reverse transcription-polymerase chain reaction. RESULTS: The model produced significant liver injury with elevated transaminases and an acute inflammatory response. Bucillamine reduced the liver injury, as indicated by reduced AST (932 ± 200.8 vs 2072.5 ± 511.79, P < 0.05). Bucillamine reduced Bax expression, serum CINC-1 levels, and neutrophil adhesion, and upregulated Bcl-2. However, bucillamine did not affect tissue glutathione levels nor the levels of oxidative stress, as measured by plasma and hepatic F(2) isoprostane levels. CONCLUSIONS: Bucillamine reduces warm ischemia-reperfusion in the liver by inhibiting neutrophil activation and modulating Bax/Bcl-2 expression.

Liver ischemia/reperfusion injury: processes in inflammatory networks--a review.

Liver ischemia/reperfusion (IR) injury is typified by an inflammatory response. Understanding the cellular and molecular events underpinning this inflammation is fundamental to developing therapeutic strategies. Great strides have been made in this respect recently. Liver IR involves a complex web of interactions between the various cellular and humoral contributors to the inflammatory response. Kupffer cells, CD4+ lymphocytes, neutrophils, and hepatocytes are central cellular players. Various cytokines, chemokines, and complement proteins form the communication system between the cellular components. The contribution of the danger-associated molecular patterns and pattern recognition receptors to the pathophysiology of liver IR injury are slowly being elucidated. Our knowledge on the role of mitochondria in generating reactive oxygen and nitrogen species, in contributing to ionic disturbances, and in initiating the mitochondrial permeability transition with subsequent cellular death in liver IR injury is continuously being expanded. Here, we discuss recent findings pertaining to the aforementioned factors of liver IR, and we highlight areas with gaps in our knowledge, necessitating further research.

Compartment syndrome following short saphenous varicose vein surgery: a case report.

Compartment syndrome is an infrequent but serious complication which can occur post-operatively. In our case, a patient developed severe left calf pain following short saphenous vein surgery. She underwent emergency fasciotomy and made an excellent recovery. Informed consent for varicose vein surgery should probably include the possibility of developing compartment syndrome.

Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury.

BACKGROUND: Liver transplantation involves a period of ischemia and reperfusion to the graft which leads to primary non-function and dysfunction of the liver in 5-10% of cases. Remote ischemic preconditioning (RIPC) has been shown to reduce ischemia reperfusion injury (IRI) injury to the liver and increase hepatic blood flow. We hypothesized that RIPC may directly modulate hepatic microcirculation and have investigated this using intravital microscopy. METHODS: A rat model of liver IRI was used with 45 min of partial hepatic ischemia (70%) followed by 3 h of reperfusion. Four groups of animals (Sham, IRI, RIPC+IRI, RIPC+Sham) were studied (n= 6, each group). Intravital microscopy was used to measure red blood cell (RBC) velocity, sinusoidal perfusion, sinusoidal flow and sinusoidal diameter. Neutrophil adhesion was assessed by rhodamine labeling of neutrophils and cell death using propidium iodide. RESULTS: RIPC reduced the effects of IRI by significantly increasing red blood cell velocity, sinusoidal flow and sinusoidal perfusion along with decreased neutrophil adhesion and cell death. CONCLUSIONS: Using intravital microscopy, this study demonstrates that RIPC modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a key role in the modulation of hepatic microcirculation and endothelial function.

Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury.

BACKGROUND: Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells. METHODS: The effect of bucillamine was studied in a rat model of liver ischaemia-reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM). RESULTS: The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 +/- 511.79 vs. 932 +/- 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 +/- 16.86 vs. 181.11 +/- 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001). CONCLUSION: Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.

Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review.

BACKGROUND: Restoration of blood supply to an organ after a critical period of ischemia results in parenchymal injury and dysfunction of the organ referred to as reperfusion injury. Ischemia reperfusion injury is often seen in organ transplants, major organ resections and in shock. Ischemic preconditioning (IPC) is an adaptational response of briefly ischemic tissues which serves to protect against subsequent prolonged ischemic insults and reperfusion injury. Ischemic preconditioning can be mechanical or pharmacological. Direct mechanical preconditioning in which the target organ is exposed to brief ischemia prior to prolonged ischemia has the benefit of reducing ischemia-reperfusion injury (IRI) but its main disadvantage is trauma to major vessels and stress to the target organ. Remote (inter organ) preconditioning is a recent observation in which brief ischemia of one organ has been shown to confer protection on distant organs without direct stress to the organ. AIM: To discuss the evidence for remote IPC (RIPC), underlying mechanisms and possible clinical applications of RIPC. METHODS OF SEARCH: A Pubmed search with the keywords "ischemic preconditioning," "remote preconditioning," "remote ischemic preconditioning," and "ischemia reperfusion" was done. All articles on remote preconditioning up to September 2006 have been reviewed. Relevant reference articles from within these have been selected for further discussion. RESULTS: Experimental studies have demonstrated that the heart, liver, lung, intestine, brain, kidney and limbs are capable of producing remote preconditioning when subjected to brief IR. Remote intra-organ preconditioning was first described in the heart where brief ischemia in one territory led to protection in other areas. Translation of RIPC to clinical application has been demonstrated by the use of brief forearm ischemia in preconditioning the heart prior to coronary bypass and in reducing endothelial dysfunction of the contra lateral limb. Recently protection of the heart has been demonstrated by remote hind limb preconditioning in children who underwent surgery on cardiopulmonary bypass for congenital heart disease. The RIPC stimulus presumably induces release of biochemical messengers which act either by the bloodstream or by the neurogenic pathway resulting in reduced oxidative stress and preservation of mitochondrial function. Studies have demonstrated endothelial NO, Free radicals, Kinases, Opioids, Catecholamines and K(ATP) channels as the candidate mechanism in remote preconditioning. Experiments have shown suppression of proinflammatory genes, expression of antioxidant genes and modulation of gene expression by RIPC as a novel method of IRI injury prevention. CONCLUSION: There is strong evidence to support RIPC. The underlying mechanisms and pathways need further clarification. The effective use of RIPC needs to be investigated in clinical settings.

A comparison of tumour M2-PK with carcinoembryonic antigen and CA19-9 in patients undergoing liver resection for colorectal metastases.

BACKGROUND: The currently available tumour markers used in the management of patients with colorectal metastases are of limited value. Tumour M2-pyruvate kinase (TuM2-PK), a tumour-associated isoenzyme of pyruvate kinase, is elevated in patients with gastrointestinal cancer. This study has measured TuM2-PK levels in patients before and after resection of colorectal liver metastases (CLM). MATERIALS AND METHODS: Fifty patients with CLM and no local residual disease had TuM2-PK levels measured before liver resection. In 20 patients, TuM2-PK levels were repeated at 2 weeks, 5 weeks and 5 months after resection. Plasma levels were analysed by enzyme-linked immunosorbent assay (ScheBo, Giessen, Germany). Carcinoembryonic antigen (CEA) and CA19-9 levels were measured at the same time periods by electrochemiluminescence immunoassay. CEA, CA19-9 and TuM2-PK levels were compared with the tumour number, volume, differentiation and stage. Cut-off values used for TuM2-PK, CEA and CA19-9 were 15 IU/ml, 10 ng/ml and 39 IU/ml, respectively. RESULTS: TuM2-PK was elevated in 68%, CEA in 62% and CA19-9 in 40% of patients with CLM. TuM2-PK+CEA was elevated in 88% and TuM2-PK+CA19-9 in 78% of patients. A significant correlation was observed between tumour volume and CEA (r=0.34, P<0.05) and CA19-9 (r=0.49, P<0.005). TuM2-PK levels did not show a significant correlation with tumour differentiation, volume or the number of metastases. At 2 weeks after liver resection, CEA and CA19-9 levels had decreased to normal value in 73 and 67% of patients, respectively, but TuM2-PK remained elevated in all patients. At 5 weeks, TuM2-PK, CEA and CA19-9 levels decreased to normal in 64, 93 and 70% of patients, respectively, and at 5 months levels were normal in 58, 92 and 67%. CONCLUSION: Plasma TuM2-PK is commonly elevated in patients with CLM. Levels do not correlate with tumour volume, number or differentiation. Levels remain elevated after liver resection, the cause of which requires further investigation.

Haematogenous metastasis to ascending colon in a patient with hepatocellular carcinoma and autoimmune hepatitis.

The association of hepatocellular carcinoma with chronic active autoimmune hepatitis and haematogenous metastasis to ascending colon has not been reported previously in the literature. The patient was asymptomatic for colonic disease and the finding of colonic involvement was incidental on scans subsequently confirmed by colonoscopy. Usually hepatocellular tumour mass would involve the colon by direct contiguity. Owing to haematogenous metastasis, which is extremely rare, the colonic mass was discontiguous from hepatic tumour lesions. The unique presentation of this case and the differential diagnosis of hepatic tumours coexisting with colonic tumours are highlighted in this case report.

Inflammatory pseudotumour of the liver: the residuum of a biliary cystadenoma?

Inflammatory pseudotumour is a rare form of a liver mass. We report the case of a 28-year-old man presenting with obstructive jaundice, in whom an inflammatory pseudotumour arose with the resolution of a mucus secreting cystic liver lesion. The initial features suggested an intrahepatic cystadenoma or cystadenocarcinoma, which on its involution left a solid mass. Histopathology showed an inflammatory pseudotumour with no evidence of malignancy. A similar case has been reported recently, with the development of an inflammatory pseudotumour following collapse of a liver cyst seen on imaging. These two cases may shed some light on the origins of these rare liver lesions.

Tumour M2-pyruvate kinase: a gastrointestinal cancer marker.

BACKGROUND: Gastrointestinal cancer tumour markers are valuable in the detection of recurrence following resection or in monitoring response to chemotherapy. CEA, CA19-9, CA-50 and CA72-4 are currently available but are nonspecific and have a low sensitivity. 'Tumour M2-pyruvate kinase' was described by Eigenbrodt around 1985. In cancers the active tetrameric form of the M2 isoenzyme of pyruvate kinase converted to an inactive dimeric form by direct interaction with oncoproteins to channel glucose carbons into DNA synthesis. This review summarizes the current knowledge of this unique tumour marker with regard to its biochemistry, assay and potential use as a diagnostic and screening tool in gastrointestinal cancer. METHODS: A literature search was conducted for entries from 1980 to 2005 using PubMed and NeLH databases using tumour M2-pyruvate kinase, faecal tumour M2-pyruvate kinase, tumour metabolism, tumour markers and carcinoembryonic antigen as keywords. A total of 56 references relevant to tumour M2-pyruvate kinase were retrieved. Eighteen references were clinical studies involving plasma/faecal tumour M2-pyruvate kinase and gastrointestinal cancer. The remaining 38 references were clinical/nonclinical trials and reviews on tumour metabolism and plasma/faecal tumour M2-pyruvate kinase assay. Seven of the 18 clinical studies involved faecal M2-pyruvate kinase. Three of the 11 plasma tumour M2-pyruvate kinase studies were non-English language and were excluded. The sensitivity, specificity, positive predictive and negative predictive value for plasma/serum tumour M2-pyruvate kinase in the detection of gastrointestinal cancer was determined for each of the remaining eight studies. Data for gastrointestinal cancer M2-pyruvate kinase were compared with other gastrointestinal cancer markers. Data from three of the eight studies using a diagnostic cut-off value of 15 U/ml for ethylenediaminetetraacetic acid (EDTA) plasma tumour M2-pyruvate kinase were analysed together as a small meta-analysis. RESULTS: At a diagnostic cut-off value of 15 U/ml for tumour M2-pyruvate kinase in EDTA plasma the sensitivity, specificity, positive predictive and negative predictive value was 57.3, 89, 85.7 and 64.8%, respectively, for colorectal cancers, 62.1, 89, 88 and 64%, respectively, for gastric/oesophageal cancers and 72.5, 89, 58 and 94%, respectively, for pancreatic cancers. As a faecal marker for colorectal cancers, faecal tumour M2-pyruvate kinase has a sensitivity of 73-92% at a cut-off value of 4 U/ml as against 50% sensitivity for Guaiac faecal test. CONCLUSION: Circulating tumour M2-pyruvate kinase is more commonly elevated in oesophageal, gastric and colorectal cancer patients than conventional tumour markers. Faecal M2-pyruvate kinase is a sensitive marker of colorectal cancer. The clinical role of tumour M2-pyruvate kinase in gastrointestinal cancer management should be investigated in large-scale clinical trials.