Philip Craig - Academia.edu (original) (raw)

Papers by Philip Craig

Gastrointestinal Endoscopy, Sep 1, 2016

Gastrointestinal Endoscopy, Mar 1, 2004

Dysphagia, 2007

The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia... more The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia for solids, is relatively uncommon and its pathogenesis is unknown. The goal of this study was to describe the demographic, clinical, and endoscopic features of patients presenting with this condition, their response to esophageal dilatation, and the relationship of multiple esophageal rings to eosinophilic esophagitis. Between 1989 and June 2004, 32 patients at this adult hospital fulfilled the following inclusion criteria: (1) intermittent dysphagia for solids, (2) multiple esophageal rings at endoscopy, and (3) esophageal dilatation(s) performed. Response to esophageal dilatation was measured by need for subsequent dilatations. Seventy-five percent of the patients were male. Median age at onset of dysphagia was 21 years and at presentation 36.5 years. All had multiple rings in the proximal or midesophagus on endoscopy and had undergone a total of 73 esophageal dilatations with no esophageal perforations. Median maximal dilator size was 15 mm; however, 16% developed significant esophageal mucosal tears even with 11-mm dilators. Sixty-six percent required repeat dilatation, with the median time interval before recurrence being 8 months. Eosinophilic esophagitis (mucosal eosinophil count > 20/HPF) was present in 50% of this cohort. From this study we conclude that a multiringed esophagus causing intermittent dysphagia occurs predominantly in young males, responds well to dilatation, but repeated dilatations are often necessary. Dilatation can lead to extensive mucosal tears and should be performed with caution. Eosinophilic esophagitis is commonly but not invariably associated with this entity. Frequent relapse of dysphagia highlights the need for effective pharmacotherapy.

Dysphagia, 2007

The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia... more The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia for solids, is relatively uncommon and its pathogenesis is unknown. The goal of this study was to describe the demographic, clinical, and endoscopic features of patients presenting with this condition, their response to esophageal dilatation, and the relationship of multiple esophageal rings to eosinophilic esophagitis. Between 1989 and June 2004, 32 patients at this adult hospital fulfilled the following inclusion criteria: (1) intermittent dysphagia for solids, (2) multiple esophageal rings at endoscopy, and (3) esophageal dilatation(s) performed. Response to esophageal dilatation was measured by need for subsequent dilatations. Seventy-five percent of the patients were male. Median age at onset of dysphagia was 21 years and at presentation 36.5 years. All had multiple rings in the proximal or midesophagus on endoscopy and had undergone a total of 73 esophageal dilatations with no esophageal perforations. Median maximal dilator size was 15 mm; however, 16% developed significant esophageal mucosal tears even with 11-mm dilators. Sixty-six percent required repeat dilatation, with the median time interval before recurrence being 8 months. Eosinophilic esophagitis (mucosal eosinophil count > 20/HPF) was present in 50% of this cohort. From this study we conclude that a multiringed esophagus causing intermittent dysphagia occurs predominantly in young males, responds well to dilatation, but repeated dilatations are often necessary. Dilatation can lead to extensive mucosal tears and should be performed with caution. Eosinophilic esophagitis is commonly but not invariably associated with this entity. Frequent relapse of dysphagia highlights the need for effective pharmacotherapy.

Gastroenterology, 2014

Background: Histologic assessment is an evolving outcome measure in ulcerative colitis (UC). Many... more Background: Histologic assessment is an evolving outcome measure in ulcerative colitis (UC). Many histological indices, including the Geboes score (GS; Figure 1 top panel) and Modified Riley Score (MRS; Figure 1 bottom panel) have been used to grade disease activity and served as endpoints for clinical trials. The operating properties of these indices, including agreement have not been fully evaluated. We assessed interand intra-rater agreement of central readers for histopathological evaluation of UC disease activity.Methods: Five central readers individually evaluated 50 slides of colonic biopsies taken from patients with UC on three separate occasions at least two weeks apart using the GS, MRS and a global rating of severity based on a 100 mm visual analogue scale (VAS). Interand intra-rater agreement was measured using intraclass correlation coefficients (ICC) for each grading system and for components of acute and chronic inflammation. Results: Intra-rater ICCs (95% confidence intervals) for the total GS, MRS and VAS scores were 0.83 (0.78, 0.87), 0.72 (0.65, 0.79) and 0.79 (0.74, 0.85), respectively. Corresponding inter-rater agreement ICCs were 0.57 (0.45, 0.68), 0.49 (0.38, 0.61) and 0.61 (0.51, 0.72) (Table 1). The correlation between each central reader's VAS with GS and MRS descriptors were 0.60 (0.44, 0.76) and 0.63 (0.47, 0.77), respectively. The items with lowest ICC (highest disagreement) were granuloma (0.01), patchiness (0.20), lamina propria fibrosis (0.21), lamina propria eosinophilia (0.26), crypt abscesses (0.32), crypt destruction (0.34), surface epithelium integrity (0.35), and lamina propria neutrophils (0.37). Conclusion: There is "substantial" to "almost perfect" intra-rater agreement among histopathologists in the assessment of disease activity in UC. Inter-rater agreement was less satisfactory. The results indicate that a central reader is highly reliable for the assessment of UC histologic disease. However, differences in interpretations of the scores among readers requires further study and standardization in order to determine the optimal instrument for use in UC clinical trials. A Delphi process has been initiated to further characterize the most important sources of disagreement. Table 1. Interand Intra-rater Agreement for Index Components

Gastrointestinal Endoscopy

Gastrointestinal endoscopy, Jan 25, 2016

HPB surgery : a world journal of hepatic, pancreatic and biliary surgery, 1998

The case of a male who had an open cholecystectomy complicated by persistent bile leak from an ab... more The case of a male who had an open cholecystectomy complicated by persistent bile leak from an aberrant bile duct is presented. The persistence and volume of bile leak resulted in subsequent investigation of the biliary tree which demonstrated a cholangiocarcinoma of the right hepatic duct. This case is presented as an unusual presentation of cholangiocarcinoma and to highlight the value of modern techniques in imaging the biliary tree.

Australian and New Zealand journal of medicine, 1987

Strategies for the control of hepatitis B virus (HBV) infection rely on information about the mod... more Strategies for the control of hepatitis B virus (HBV) infection rely on information about the modes of spread and the numbers of 'at risk' individuals in particular community subgroups. This study prospectively examined 377 family and household contacts of 145 patients with HBV infection to determine the incidence of and factors determining intrafamily spread. Two hundred and forty were contacts of 68 Asian patients and 137 were contacts of 77 Caucasian patients. Serological examination of all contacts demonstrated that 161 (43%) had HBV markers including 60 (16%) who were HBsAg positive. HBV transmission within families was greater if the index case was Asian rather than Caucasian (p less than 0.001), had an HBsAg positive mother rather than an HBsAg positive father (p less than 0.01), was HBeAg positive rather than HBeAg negative (p less than 0.002), and had chronic rather than acute HBV infection (p less than 0.001). However birthplace, family size, and the activity of th...

Gastroenterology, 1989

An animal model suitable for in vivo studies of interferon-mediated suppression of hepatic oxidat... more An animal model suitable for in vivo studies of interferon-mediated suppression of hepatic oxidative drug metabolism has been developed. Rats were injected with either recombinant human interferon alpha A, recombinant human interferon gamma, recombinant rat interferon gamma, or vehicle and experiments were performed 24 h later. In some animals theophylline elimination was determined twice (10 days apart), once after interferon and once after vehicle. Theophylline clearance was also determined in the isolated perfused rat liver after pretreatment of animals with interferon or vehicle. Pretreatment of animals with rat interferon gamma significantly reduced theophylline clearance in the intact rat but neither human interferon alpha A nor human interferon gamma altered theophylline elimination in vivo. Similar results were observed in the isolated perfused rat liver. We then examined whether the effects of interferon on hepatic drug metabolism were generalized or confined to individual ...

Australian and New Zealand journal of medicine, 1990

This editorial will focus on the features of more recently identified forms of viral hepatitis, t... more This editorial will focus on the features of more recently identified forms of viral hepatitis, types C, D and E

Journal of Infection, 2002

We report a case of alveolar echinococcosis. To our knowledge this is the first report of human a... more We report a case of alveolar echinococcosis. To our knowledge this is the first report of human alveolar echinococcosis to be confirmed in the UK and if contracted in Afghanistan the first report for that country.

Journal of Gastroenterology and Hepatology, 2007

A 29-year-old man with previous neonatal meningitis and spastic quadriplegia required feeding by ... more A 29-year-old man with previous neonatal meningitis and spastic quadriplegia required feeding by percutaneous endoscopic gastrostomy (PEG) because of a poor oral intake. As a standard PEG placement was impossible due to severe postural contractures and a large hiatus hernia, a 20F PEG tube was placed using a combined endoscopic and radiological approach. As the stomach was largely intrathoracic, it was inadvertently accessed via the left 11th intercostal space and placement was initially complicated by a pneumothorax and pneumoperitoneum. The PEG tube functioned well for 6 months but, thereafter, the patient became distressed during feeding. A PEG tubogram and endoscopy confirmed migration of the bumper out of the stomach but, with traction to remove the tube, it became disconnected from the bumper. To avoid a thoracotomy, the bumper was left in situ between the gastric wall and ribs and a new PEG was inserted through the existing tract. Seven months later, use of the second PEG also became difficult. At gastroscopy, the buried PEG appeared as a protrusion in the gastric body. A computed tomography scan was performed (Fig. 1). Endoscopic removal of the PEG involved an incision of the overlying gastric mucosa with a needle-knife papillotome, dilatation of the tract using an 18 mm wire-guided dilating balloon and extraction of the bumpers through the stomach. The bumper from the initial PEG was found attached to the second PEG tube (Fig. 2). A 20F Ballard gastrostomy tube with an internal balloon was then positioned over a wire through the existing tract. The patient has remained well on follow-up for 2 years. Migration of the internal flange or PEG bumper out of the stomach is termed the buried bumper syndrome. This is usually due to excessive external traction on the PEG tube from a tight external flange that causes the bumper to erode through the gastric wall. In our case, rib fixation and continual respiratory movements seems likely to have contributed to the two episodes of buried bumper syndrome. Typical methods to remove buried bumpers involve the use of snares, grasping forceps, Savary dilators and modified PEG tube sets. However, in the above patient, these approaches were unlikely to have been successful and surgery would have required a thoracotomy. The combination of needle-knife incision of the gastric wall to expose the buried bumpers and balloon dilatation to enlarge the tract and pull the bumpers into the stomach does not appear to have been described previously.

Journal of Gastroenterology and Hepatology, 2008

symptomatic progression with sorafenib versus placebo. However, the overall survival rate was fou... more symptomatic progression with sorafenib versus placebo. However, the overall survival rate was found to be significantly longer in sorafenib-treated patients compared with those taking placebo (median survival: 46 weeks vs 34 weeks, respectively, P = 0.00058), representing a 44% improvement in overall survival (hazard ratio, 0.69). In addition, sorafenib significantly improved the time to disease progression compared to placebo (24 weeks vs 12 weeks, respectively, P = 0.000007), indicating a 73% prolongation in the time to disease progression (hazard ratio, 0.58). The most common treatment-related adverse events with sorafenib were diarrhea, rash/desquamation, fatigue, hand and foot skin reactions, alopecia, and nausea. However, dose limiting toxicities were infrequent. It was concluded that sorafenib as a single agent offered considerable efficacy in advanced HCC with reasonable toxicity. This study has established sorafenib as the new standard treatment of patients with advanced HCC. Sorafenib is the first US Food and Drug Administration approved systemic therapy in patients with advanced HCC. This effect is clinically meaningful, and establishes sorafenib as a control arm for clinical trials. However, the safety and efficacy of sorafenib in patients with significant hepatic dysfunction, such as Child-Pugh Class B or C cirrhosis, are still unknown. In conclusion, the need for more effective systemic therapies for patients with advanced HCC is clearly evident. A growing understanding of the pathways involved in the initiation and promotion of hepatocarcinogenesis may ultimately lead to novel therapies that demonstrate significant improvement in survival. Also, it is particularly important that well-designed and adequately powered clinical trials will hopefully are designed to clearly elucidate the role of chemotherapeutic agents in HCC.

Journal of Gastroenterology and Hepatology, 1986

Key words: computerized tomography, fine needle aspiration, liver abscess, liver abscess amoebic,... more Key words: computerized tomography, fine needle aspiration, liver abscess, liver abscess amoebic, liver resection, percutaneous drainage. ... Correspondence: Professor JM Little, Department of Surgery, Westmead Hospital, Westmead, NSW 2145, Australia.

Hepatology, 1993

Interferon down-regulates expression of cytochrome P-450 3A in male rats. This study explored the... more Interferon down-regulates expression of cytochrome P-450 3A in male rats. This study explored the hypothesis that interferon therefore decreases the metabolism of drugs catalyzed by cytochrome P-450 3A. Initial experiments in male rats used microsomal erythromycin N-demethylase activity as a probe for cytochrome P-450 3A catalytic activity. After administration of rat interferon-gamma, erythromycin metabolism was impaired (53% of control; p < 0.01). This change correlated with the decline in cytochrome P-450 3A-dependent androstenedione 6 beta-hydroxylase activity, indicating that the decrease in erythromycin N-demethylase activity could be attributed to interferon-mediated suppression of cytochrome P-450 3A. We then used the [14C]N-methyl erythromycin breath test to assess the activity of hepatic cytochrome P-450 3A in rats and human subjects before and after a single dose of interferon. In rats, rat interferon-gamma decreased erythromycin metabolism to 57% of control (p < 0.005). In the human study, six patients with chronic active hepatitis C and four healthy controls were examined 20 to 26 hr after receiving a subcutaneous injection of human interferon-alpha 2b. Interferon produced a small decrease (median = 15%; range = 3% to 35%) in erythromycin metabolism (p < 0.05), as determined by 2-hr excretion of 14CO2 in the breath. Thus interferon-mediated suppression of cytochrome P-450 3A is less strong in human subjects than in male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastrointestinal Endoscopy, 2000

Gastrointestinal Endoscopy, 1996

Effective palliation of malignant biliary obstruction with conventional 10 or 12 French gauge str... more Effective palliation of malignant biliary obstruction with conventional 10 or 12 French gauge straight polyethylene endoprostheses is limited by stent occlusion, which typically occurs four to five months after insertion. Short term follow up studies of self expanding metal stents (Wallstent, Schneider, UK) in the treatment of patients with malignant biliary obstruction have shown that their use is associated with fewer episodes of stent occlusion compared with plastic stents. There are few data, however, on the longterm patency and durability of metal stents in malignant disease. Between May 1989 and May 1992, metal stents were inserted in 28 patients with malignant bile duct strictures secondary to ampullary tumour (n =10), pancreatic carcinoma (n=10), cholangiocarcinoma (n=7), and porta hepatis nodes from colorectal carcinoma (n=1). The follow up of these patients until May 1993 is reported with a median follow up of 14-6 months. Twenty two of 28 (78.6%) patients remained free of jaundice or cholangitis. The median period of stent patency was 8.2 months (range 1.0-32.5). Thirteen patients represented with jaundice or cholangitis and endoscopic retrograde cholangiopancreatography showed evidence of stent occlusion due to tumour ingrowth. Successful clearance of metal stents was achieved by balloon trawling, or insertion of a polyethylene stent. In conclusion, metal stents provide improved longterm palliation for patients with malignant biliary strictures with fewer episodes of occlusion compared with conventional stents.

Gastrointestinal Endoscopy, 2013

A. Small broad-based subepithelial tumor in the gastric body. B. Miniloop ligation using the 18mm... more A. Small broad-based subepithelial tumor in the gastric body. B. Miniloop ligation using the 18mm transparent 'EMR' cap. C. Post-ligation unroofing with a needle knife. Biopsies showed a GIST. D. Scar at site of loop ligation. No residual tumor seen on EUS.

Gastrointestinal Endoscopy, Sep 1, 2016

Gastrointestinal Endoscopy, Mar 1, 2004

Dysphagia, 2007

The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia... more The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia for solids, is relatively uncommon and its pathogenesis is unknown. The goal of this study was to describe the demographic, clinical, and endoscopic features of patients presenting with this condition, their response to esophageal dilatation, and the relationship of multiple esophageal rings to eosinophilic esophagitis. Between 1989 and June 2004, 32 patients at this adult hospital fulfilled the following inclusion criteria: (1) intermittent dysphagia for solids, (2) multiple esophageal rings at endoscopy, and (3) esophageal dilatation(s) performed. Response to esophageal dilatation was measured by need for subsequent dilatations. Seventy-five percent of the patients were male. Median age at onset of dysphagia was 21 years and at presentation 36.5 years. All had multiple rings in the proximal or midesophagus on endoscopy and had undergone a total of 73 esophageal dilatations with no esophageal perforations. Median maximal dilator size was 15 mm; however, 16% developed significant esophageal mucosal tears even with 11-mm dilators. Sixty-six percent required repeat dilatation, with the median time interval before recurrence being 8 months. Eosinophilic esophagitis (mucosal eosinophil count > 20/HPF) was present in 50% of this cohort. From this study we conclude that a multiringed esophagus causing intermittent dysphagia occurs predominantly in young males, responds well to dilatation, but repeated dilatations are often necessary. Dilatation can lead to extensive mucosal tears and should be performed with caution. Eosinophilic esophagitis is commonly but not invariably associated with this entity. Frequent relapse of dysphagia highlights the need for effective pharmacotherapy.

Dysphagia, 2007

The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia... more The entity of the multiringed esophagus, generally presenting in adults as intermittent dysphagia for solids, is relatively uncommon and its pathogenesis is unknown. The goal of this study was to describe the demographic, clinical, and endoscopic features of patients presenting with this condition, their response to esophageal dilatation, and the relationship of multiple esophageal rings to eosinophilic esophagitis. Between 1989 and June 2004, 32 patients at this adult hospital fulfilled the following inclusion criteria: (1) intermittent dysphagia for solids, (2) multiple esophageal rings at endoscopy, and (3) esophageal dilatation(s) performed. Response to esophageal dilatation was measured by need for subsequent dilatations. Seventy-five percent of the patients were male. Median age at onset of dysphagia was 21 years and at presentation 36.5 years. All had multiple rings in the proximal or midesophagus on endoscopy and had undergone a total of 73 esophageal dilatations with no esophageal perforations. Median maximal dilator size was 15 mm; however, 16% developed significant esophageal mucosal tears even with 11-mm dilators. Sixty-six percent required repeat dilatation, with the median time interval before recurrence being 8 months. Eosinophilic esophagitis (mucosal eosinophil count > 20/HPF) was present in 50% of this cohort. From this study we conclude that a multiringed esophagus causing intermittent dysphagia occurs predominantly in young males, responds well to dilatation, but repeated dilatations are often necessary. Dilatation can lead to extensive mucosal tears and should be performed with caution. Eosinophilic esophagitis is commonly but not invariably associated with this entity. Frequent relapse of dysphagia highlights the need for effective pharmacotherapy.

Gastroenterology, 2014

Background: Histologic assessment is an evolving outcome measure in ulcerative colitis (UC). Many... more Background: Histologic assessment is an evolving outcome measure in ulcerative colitis (UC). Many histological indices, including the Geboes score (GS; Figure 1 top panel) and Modified Riley Score (MRS; Figure 1 bottom panel) have been used to grade disease activity and served as endpoints for clinical trials. The operating properties of these indices, including agreement have not been fully evaluated. We assessed interand intra-rater agreement of central readers for histopathological evaluation of UC disease activity.Methods: Five central readers individually evaluated 50 slides of colonic biopsies taken from patients with UC on three separate occasions at least two weeks apart using the GS, MRS and a global rating of severity based on a 100 mm visual analogue scale (VAS). Interand intra-rater agreement was measured using intraclass correlation coefficients (ICC) for each grading system and for components of acute and chronic inflammation. Results: Intra-rater ICCs (95% confidence intervals) for the total GS, MRS and VAS scores were 0.83 (0.78, 0.87), 0.72 (0.65, 0.79) and 0.79 (0.74, 0.85), respectively. Corresponding inter-rater agreement ICCs were 0.57 (0.45, 0.68), 0.49 (0.38, 0.61) and 0.61 (0.51, 0.72) (Table 1). The correlation between each central reader's VAS with GS and MRS descriptors were 0.60 (0.44, 0.76) and 0.63 (0.47, 0.77), respectively. The items with lowest ICC (highest disagreement) were granuloma (0.01), patchiness (0.20), lamina propria fibrosis (0.21), lamina propria eosinophilia (0.26), crypt abscesses (0.32), crypt destruction (0.34), surface epithelium integrity (0.35), and lamina propria neutrophils (0.37). Conclusion: There is "substantial" to "almost perfect" intra-rater agreement among histopathologists in the assessment of disease activity in UC. Inter-rater agreement was less satisfactory. The results indicate that a central reader is highly reliable for the assessment of UC histologic disease. However, differences in interpretations of the scores among readers requires further study and standardization in order to determine the optimal instrument for use in UC clinical trials. A Delphi process has been initiated to further characterize the most important sources of disagreement. Table 1. Interand Intra-rater Agreement for Index Components

Gastrointestinal Endoscopy

Gastrointestinal endoscopy, Jan 25, 2016

HPB surgery : a world journal of hepatic, pancreatic and biliary surgery, 1998

The case of a male who had an open cholecystectomy complicated by persistent bile leak from an ab... more The case of a male who had an open cholecystectomy complicated by persistent bile leak from an aberrant bile duct is presented. The persistence and volume of bile leak resulted in subsequent investigation of the biliary tree which demonstrated a cholangiocarcinoma of the right hepatic duct. This case is presented as an unusual presentation of cholangiocarcinoma and to highlight the value of modern techniques in imaging the biliary tree.

Australian and New Zealand journal of medicine, 1987

Strategies for the control of hepatitis B virus (HBV) infection rely on information about the mod... more Strategies for the control of hepatitis B virus (HBV) infection rely on information about the modes of spread and the numbers of 'at risk' individuals in particular community subgroups. This study prospectively examined 377 family and household contacts of 145 patients with HBV infection to determine the incidence of and factors determining intrafamily spread. Two hundred and forty were contacts of 68 Asian patients and 137 were contacts of 77 Caucasian patients. Serological examination of all contacts demonstrated that 161 (43%) had HBV markers including 60 (16%) who were HBsAg positive. HBV transmission within families was greater if the index case was Asian rather than Caucasian (p less than 0.001), had an HBsAg positive mother rather than an HBsAg positive father (p less than 0.01), was HBeAg positive rather than HBeAg negative (p less than 0.002), and had chronic rather than acute HBV infection (p less than 0.001). However birthplace, family size, and the activity of th...

Gastroenterology, 1989

An animal model suitable for in vivo studies of interferon-mediated suppression of hepatic oxidat... more An animal model suitable for in vivo studies of interferon-mediated suppression of hepatic oxidative drug metabolism has been developed. Rats were injected with either recombinant human interferon alpha A, recombinant human interferon gamma, recombinant rat interferon gamma, or vehicle and experiments were performed 24 h later. In some animals theophylline elimination was determined twice (10 days apart), once after interferon and once after vehicle. Theophylline clearance was also determined in the isolated perfused rat liver after pretreatment of animals with interferon or vehicle. Pretreatment of animals with rat interferon gamma significantly reduced theophylline clearance in the intact rat but neither human interferon alpha A nor human interferon gamma altered theophylline elimination in vivo. Similar results were observed in the isolated perfused rat liver. We then examined whether the effects of interferon on hepatic drug metabolism were generalized or confined to individual ...

Australian and New Zealand journal of medicine, 1990

This editorial will focus on the features of more recently identified forms of viral hepatitis, t... more This editorial will focus on the features of more recently identified forms of viral hepatitis, types C, D and E

Journal of Infection, 2002

We report a case of alveolar echinococcosis. To our knowledge this is the first report of human a... more We report a case of alveolar echinococcosis. To our knowledge this is the first report of human alveolar echinococcosis to be confirmed in the UK and if contracted in Afghanistan the first report for that country.

Journal of Gastroenterology and Hepatology, 2007

A 29-year-old man with previous neonatal meningitis and spastic quadriplegia required feeding by ... more A 29-year-old man with previous neonatal meningitis and spastic quadriplegia required feeding by percutaneous endoscopic gastrostomy (PEG) because of a poor oral intake. As a standard PEG placement was impossible due to severe postural contractures and a large hiatus hernia, a 20F PEG tube was placed using a combined endoscopic and radiological approach. As the stomach was largely intrathoracic, it was inadvertently accessed via the left 11th intercostal space and placement was initially complicated by a pneumothorax and pneumoperitoneum. The PEG tube functioned well for 6 months but, thereafter, the patient became distressed during feeding. A PEG tubogram and endoscopy confirmed migration of the bumper out of the stomach but, with traction to remove the tube, it became disconnected from the bumper. To avoid a thoracotomy, the bumper was left in situ between the gastric wall and ribs and a new PEG was inserted through the existing tract. Seven months later, use of the second PEG also became difficult. At gastroscopy, the buried PEG appeared as a protrusion in the gastric body. A computed tomography scan was performed (Fig. 1). Endoscopic removal of the PEG involved an incision of the overlying gastric mucosa with a needle-knife papillotome, dilatation of the tract using an 18 mm wire-guided dilating balloon and extraction of the bumpers through the stomach. The bumper from the initial PEG was found attached to the second PEG tube (Fig. 2). A 20F Ballard gastrostomy tube with an internal balloon was then positioned over a wire through the existing tract. The patient has remained well on follow-up for 2 years. Migration of the internal flange or PEG bumper out of the stomach is termed the buried bumper syndrome. This is usually due to excessive external traction on the PEG tube from a tight external flange that causes the bumper to erode through the gastric wall. In our case, rib fixation and continual respiratory movements seems likely to have contributed to the two episodes of buried bumper syndrome. Typical methods to remove buried bumpers involve the use of snares, grasping forceps, Savary dilators and modified PEG tube sets. However, in the above patient, these approaches were unlikely to have been successful and surgery would have required a thoracotomy. The combination of needle-knife incision of the gastric wall to expose the buried bumpers and balloon dilatation to enlarge the tract and pull the bumpers into the stomach does not appear to have been described previously.

Journal of Gastroenterology and Hepatology, 2008

symptomatic progression with sorafenib versus placebo. However, the overall survival rate was fou... more symptomatic progression with sorafenib versus placebo. However, the overall survival rate was found to be significantly longer in sorafenib-treated patients compared with those taking placebo (median survival: 46 weeks vs 34 weeks, respectively, P = 0.00058), representing a 44% improvement in overall survival (hazard ratio, 0.69). In addition, sorafenib significantly improved the time to disease progression compared to placebo (24 weeks vs 12 weeks, respectively, P = 0.000007), indicating a 73% prolongation in the time to disease progression (hazard ratio, 0.58). The most common treatment-related adverse events with sorafenib were diarrhea, rash/desquamation, fatigue, hand and foot skin reactions, alopecia, and nausea. However, dose limiting toxicities were infrequent. It was concluded that sorafenib as a single agent offered considerable efficacy in advanced HCC with reasonable toxicity. This study has established sorafenib as the new standard treatment of patients with advanced HCC. Sorafenib is the first US Food and Drug Administration approved systemic therapy in patients with advanced HCC. This effect is clinically meaningful, and establishes sorafenib as a control arm for clinical trials. However, the safety and efficacy of sorafenib in patients with significant hepatic dysfunction, such as Child-Pugh Class B or C cirrhosis, are still unknown. In conclusion, the need for more effective systemic therapies for patients with advanced HCC is clearly evident. A growing understanding of the pathways involved in the initiation and promotion of hepatocarcinogenesis may ultimately lead to novel therapies that demonstrate significant improvement in survival. Also, it is particularly important that well-designed and adequately powered clinical trials will hopefully are designed to clearly elucidate the role of chemotherapeutic agents in HCC.

Journal of Gastroenterology and Hepatology, 1986

Key words: computerized tomography, fine needle aspiration, liver abscess, liver abscess amoebic,... more Key words: computerized tomography, fine needle aspiration, liver abscess, liver abscess amoebic, liver resection, percutaneous drainage. ... Correspondence: Professor JM Little, Department of Surgery, Westmead Hospital, Westmead, NSW 2145, Australia.

Hepatology, 1993

Interferon down-regulates expression of cytochrome P-450 3A in male rats. This study explored the... more Interferon down-regulates expression of cytochrome P-450 3A in male rats. This study explored the hypothesis that interferon therefore decreases the metabolism of drugs catalyzed by cytochrome P-450 3A. Initial experiments in male rats used microsomal erythromycin N-demethylase activity as a probe for cytochrome P-450 3A catalytic activity. After administration of rat interferon-gamma, erythromycin metabolism was impaired (53% of control; p < 0.01). This change correlated with the decline in cytochrome P-450 3A-dependent androstenedione 6 beta-hydroxylase activity, indicating that the decrease in erythromycin N-demethylase activity could be attributed to interferon-mediated suppression of cytochrome P-450 3A. We then used the [14C]N-methyl erythromycin breath test to assess the activity of hepatic cytochrome P-450 3A in rats and human subjects before and after a single dose of interferon. In rats, rat interferon-gamma decreased erythromycin metabolism to 57% of control (p < 0.005). In the human study, six patients with chronic active hepatitis C and four healthy controls were examined 20 to 26 hr after receiving a subcutaneous injection of human interferon-alpha 2b. Interferon produced a small decrease (median = 15%; range = 3% to 35%) in erythromycin metabolism (p < 0.05), as determined by 2-hr excretion of 14CO2 in the breath. Thus interferon-mediated suppression of cytochrome P-450 3A is less strong in human subjects than in male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastrointestinal Endoscopy, 2000

Gastrointestinal Endoscopy, 1996

Effective palliation of malignant biliary obstruction with conventional 10 or 12 French gauge str... more Effective palliation of malignant biliary obstruction with conventional 10 or 12 French gauge straight polyethylene endoprostheses is limited by stent occlusion, which typically occurs four to five months after insertion. Short term follow up studies of self expanding metal stents (Wallstent, Schneider, UK) in the treatment of patients with malignant biliary obstruction have shown that their use is associated with fewer episodes of stent occlusion compared with plastic stents. There are few data, however, on the longterm patency and durability of metal stents in malignant disease. Between May 1989 and May 1992, metal stents were inserted in 28 patients with malignant bile duct strictures secondary to ampullary tumour (n =10), pancreatic carcinoma (n=10), cholangiocarcinoma (n=7), and porta hepatis nodes from colorectal carcinoma (n=1). The follow up of these patients until May 1993 is reported with a median follow up of 14-6 months. Twenty two of 28 (78.6%) patients remained free of jaundice or cholangitis. The median period of stent patency was 8.2 months (range 1.0-32.5). Thirteen patients represented with jaundice or cholangitis and endoscopic retrograde cholangiopancreatography showed evidence of stent occlusion due to tumour ingrowth. Successful clearance of metal stents was achieved by balloon trawling, or insertion of a polyethylene stent. In conclusion, metal stents provide improved longterm palliation for patients with malignant biliary strictures with fewer episodes of occlusion compared with conventional stents.

Gastrointestinal Endoscopy, 2013

A. Small broad-based subepithelial tumor in the gastric body. B. Miniloop ligation using the 18mm... more A. Small broad-based subepithelial tumor in the gastric body. B. Miniloop ligation using the 18mm transparent 'EMR' cap. C. Post-ligation unroofing with a needle knife. Biopsies showed a GIST. D. Scar at site of loop ligation. No residual tumor seen on EUS.