Aali J. Sheen

Antioxidant Therapy Does Not Reduce Pain in Patients With Chronic Pancreatitis: The ANTICIPATE Study

BACKGROUND & AIMS We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. METHODS We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol. RESULTS After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, β-carotene, and selenium were increased significantly in the antioxidant group. CONCLUSIONS Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants.

The End of Cryotherapy for the Treatment of Nonresectable Hepatic Tumors

Liver resection is generally accepted as the standard of care for patients with hepatic metastases from colorectal tumors in the absence of extrahepatic disease and for selected patients with primary hepatocellular carcinoma. However, in any given cohort of patients with hepatic tumors, most will be unsuitable for resection because of the extent of hepatic tumor burden, extrahepatic disease, or comorbidity. Treatment options in this setting include systemic modalities such as chemotherapy, regional interventions such as intra-arterial chemotherapy, and direct tumor ablation. Direct ablative treatments include intratumoral ethanol, laser, cryotherapy, and, more recently, radiofrequency ablation. Until the advent of radiofrequency, direct intratumoral ethanol and cryotherapy were perhaps the most widely used ablative approaches. Ethanol can be injected percutaneously and does not rely on costly equipment for delivery, and treatments can be repeated. Cryotherapy uses liquid nitrogen at )196 C delivered through a closed triplelumen probe and relies on cooling of liver tumors to at least )35 C. Tumor cell death occurs as a consequence of the formation of intracellular crystals during rapid freezing. Although widely used over the past decade, cryotherapy for liver tumors is not without problems. Freezing can lead to cracking or shearing of the liver parenchyma, andmajor hemorrhage results if these shearing injuries extend into major vessels. Late hemorrhage and intrahepatic abscesses related to biliary injury are also recognized complications. In addition to these local effects of cryotherapy, there are systemic side effects: the cytokine-mediated systemic illness associated with cryotherapy is characterized by fever, tachycardia, and tachypnea. This is known as the cryoshock syndrome and, in particular, can be associated with pleural effusion, diffuse lung injury, and acute renal tubular necrosis. The role of cryotherapy has become increasingly challenged since the advent of radiofrequency thermal ablation. This technique involves the passage of alternating high-frequency current (typically 10 kHz) through tissue. The molecular agitation caused by high-frequency energy leads to an increase in temperature in the tissue through which the current passes without causing muscle contraction or pain. If the field is applied between two equal-sized electrodes, the current flow per unit area of the electrode (current density) is similar in both electrodes. However, if one electrode is smaller, then, because the same total amount of current still has to flow, the current density is much higher at the smaller electrode, with a correspondingly higher temperature. Commercial availability of cooled-tip multiprobe electrodes equipped with probe-tip thermal sensors now permits the creation of a precise hepatic parenchymal ablation. In an important study, Scudamore et al. performed radiofrequency ablation of resectable liver tumors in 10 patients (7 patients with colorectal liver metastases) and then undertook liver resection in 9 of these individuals within 6 weeks of the ablation. On histological examination of the resected specimen by using nicotinamide adenine dinucleotide (NADH; a histochemical technique for demonstration of tissue oxidative enzyme activity), ablated tissue was recognized in all nine cases. The Received October 15, 2004; accepted December 2, 2004; published online March 3, 2005. Address correspondence and reprint requests to: Ajith K. Siriwardena, MD, FRCS; E-mail: ajith.siriwardena@cmmc.nhs.uk.Liver resection is generally accepted as the standard of care for patients with hepatic metastases from colorectal tumors in the absence of extrahepatic disease and for selected patients with primary hepatocellular carcinoma. However, in any given cohort of patients with hepatic tumors, most will be unsuitable for resection because of the extent of hepatic tumor burden, extrahepatic disease, or comorbidity. Treatment options in this setting include systemic modalities such as chemotherapy, regional interventions such as intra-arterial chemotherapy, and direct tumor ablation. Direct ablative treatments include intratumoral ethanol, laser, cryotherapy, and, more recently, radiofrequency ablation. Until the advent of radiofrequency, direct intratumoral ethanol and cryotherapy were perhaps the most widely used ablative approaches. Ethanol can be injected percutaneously and does not rely on costly equipment for delivery, and treatments can be repeated. Cryotherapy uses liquid nitrogen at )196 C delivered through a closed triplelumen probe and relies on cooling of liver tumors to at least )35 C. Tumor cell death occurs as a consequence of the formation of intracellular crystals during rapid freezing. Although widely used over the past decade, cryotherapy for liver tumors is not without problems. Freezing can lead to cracking or shearing of the liver parenchyma, andmajor hemorrhage results if these shearing injuries extend into major vessels. Late hemorrhage and intrahepatic abscesses related to biliary injury are also recognized complications. In addition to these local effects of cryotherapy, there are systemic side effects: the cytokine-mediated systemic illness associated with cryotherapy is characterized by fever, tachycardia, and tachypnea. This is known as the cryoshock syndrome and, in particular, can be associated with pleural effusion, diffuse lung injury, and acute renal tubular necrosis. The role of cryotherapy has become increasingly challenged since the advent of radiofrequency thermal ablation. This technique involves the passage of alternating high-frequency current (typically 10 kHz) through tissue. The molecular agitation caused by high-frequency energy leads to an increase in temperature in the tissue through which the current passes without causing muscle contraction or pain. If the field is applied between two equal-sized electrodes, the current flow per unit area of the electrode (current density) is similar in both electrodes. However, if one electrode is smaller, then, because the same total amount of current still has to flow, the current density is much higher at the smaller electrode, with a correspondingly higher temperature. Commercial availability of cooled-tip multiprobe electrodes equipped with probe-tip thermal sensors now permits the creation of a precise hepatic parenchymal ablation. In an important study, Scudamore et al. performed radiofrequency ablation of resectable liver tumors in 10 patients (7 patients with colorectal liver metastases) and then undertook liver resection in 9 of these individuals within 6 weeks of the ablation. On histological examination of the resected specimen by using nicotinamide adenine dinucleotide (NADH; a histochemical technique for demonstration of tissue oxidative enzyme activity), ablated tissue was recognized in all nine cases. The Received October 15, 2004; accepted December 2, 2004; published online March 3, 2005. Address correspondence and reprint requests to: Ajith K. Siriwardena, MD, FRCS; E-mail: ajith.siriwardena@cmmc.nhs.uk.

Systematic review: laparoscopic treatment of long-standing groin pain in athletes

Objectives No single aetiological factor has been proven to cause long-standing groin pain in athletes and no sole operative technique (either open or laparoscopic) has been shown to be the preferred method of repair. The aim of this systematic review was to determine whether there are any differences in the return to full sporting activity following laparoscopic repair of groin pain in athletes. Data sources The minimal access approaches include laparoscopic transabdominal pre-peritoneal (TAPP) or endoscopic total extraperitoneal (TEP) techniques. A systematic literature search was performed in PubMed, SCOPUS, UpToDate and the Cochrane Library databases. Series reporting laparoscopic repair (TAPP/TEP) of groin pain in adult (>18 years) athletes were included. The primary outcome was return to full sporting activity and secondary outcomes included percentage success rates and complications of operations. Results Only 18 studies fulfilled the search criteria with both laparoscopic and sports hernia repairs. The studies were mainly observational with some reporting comparative data, but no large randomised controlled trials were detected. The median return to sporting activity of 4 weeks (28 days) was the same for the TAPP as well as TEP techniques. No real difference in secondary outcome measures was shown. More reported cases to date in the literature used the TAPP technique compared with TEP repair (n=605 vs n=266). Conclusions Laparoscopic surgery for elite athlete groin pain is increasingly becoming more common with almost 1000 patients reported since 1997. No particular laparoscopic technique appears to offer any advantage over the other.

Twenty-four hour infusion of human recombinant activated protein C (Xigris) early in severe acute pancreatitis: The XIG-AP 1 trial.

OBJECTIVE Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 μg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION Eudract Number 2007-003635-23.

Contemporary management of ‘Inguinal disruption’ in the sportsman’s groin

BackgroundThis article helps define the basic principles to diagnosis and manage one of the surgically correctable causes of the ‘painful groin’, which is commonly described as the sportsman’s groin.DiscussionOften many surgeons will describe a single pathology for the sportsman’s groin such as a ‘hernia’ but often other coexisting etiologies may be present.Management relies on a multidisciplinary approach with a diagnosis initially made by a history of pain in the groin on exercise. Physiotherapy is the recommended first line treatment and is designed to concentrate on strengthening of the abdominal wall muscle and tendon groups around the groin area.Surgery does have a role in the sportsman’s groin but only once all conservative measures have been exhausted or if there is a clear identified pathology causing the groin symptoms such as posterior wall defect.Surgical principles for an inguinal disruption include either open or laparoscopic techniques reinforcing the inguinal canal with a mesh or suture repair followed by an active rehabilitation programme.SummaryOnce an accurate diagnosis has been achieved, contemporary guidance for inguinal disruption requires a multidisciplinary approach including a specially designed physiotherapy regime and possibly surgery.

Impact of portal vein embolization on long-term survival of patients with primarily unresectable colorectal liver metastases (Br J Surg 2010; 97: 240-250).

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Copyright

Preventing Inguinodynia After Hernia Surgery: Does the Type of Mesh Matter?

To the editor, We, the authors, read with interest the comments from Pellino and Selvaggi on our article [1]. We agree with the observation from Pellino et al. and colleagues that surgical expertise, method of mesh fixation as well as type of mesh used is likely to be the determining factor in post-operative chronic pain [2]. It is though mooted but remains to be demonstrated in any randomized controlled trial as to whether a patient’s relative weight and body mass index may determine mesh comfort, especially as ‘thin’ patients may more inclined to experience a foreign body sensation? Our study does demonstrate that fixation is a key factor with traumatic fixation being more inclined to result in increased post-operative discomfort. Further work is still required with trials aiming at long-term follow-up, however from previous studies and experience it would seem reasonable to predict that long-term follow-up may show little significant difference [3].

Letter 2: Randomized clinical trial of routine on‐table cholangiography during laparoscopic cholecystectomy (Br J Surg 2011; 98: 362–367)

Sir We read with interest the paper by Gruber-Blum and colleagues. Three different separate antiadhesive barriers (SABs) fixed to a polypropylene mesh with fibrin glue were compared. A bias exists as the SABs were fixed to the mesh with fibrin glue, whereas the mesh was not covered with glue in the control group. In effect, fibrin glue could have interfered with the inflammatory response. Fibrin sealant is known to be completely biodegradable, and to have adhesive and haemostatic effects1. This study failed to prove that it did not influence in any manner the antiadhesive or even the adhesive process. In order to demonstrate this conclusively, a ‘nude’ mesh should be compared at 7 and 30 days with another mesh covered with fibrin sealant in this particular instance. Furthermore, although two of the three SABs showed fewer adhesions, they also showed less tissue integration, which may impair abdominal wall reinforcement2. Moreover, tissue integration was very disparate with the use of small 4-cm2 meshes fixed with four sutures. Thus, no conclusion can be drawn from the data presented as it is known that incorporation between mesh and abdominal wall is often only seen at the fixing sutures2. Surprisingly, mesh covered with cellulose (Seprafilm; Genzyme, Cambridge, Massachusetts, USA) showed significantly fewer adhesions, but had the same foreign body reaction as the others (including control). This is in contrast to findings when mesh with a similar type of ‘coating’ (Proceed; Ethicon, Johnson & Johnson, Somerville, New Jersey, USA) was used2; large numbers of macrophages degrading remnants of cellulose coating and disorganized fibroblasts were found, without signs of granulation. S. Aellen, M. Cotton, N. Demartines, H. Vuilleumier University Hospital of Lausanne, CHUV, Lausanne, SwitzerlandHB (e-mail: steve.aellen@chuv.ch) DOI: 10.1002/bjs.7548

Colorectal Liver Metastases

Colorectal cancer can metastasize to the liver by three potential routes; the most common are via the portal venous drainage of the liver and the lymphatic drainage of the large intestine with a third mechanism being direct invasion of the liver by a tumor of the hepatic flexure [1].