T. R. Kurzawinski

Phase II Study of Anti–Gastrin-17 Antibodies, Raised to G17DT, in Advanced Pancreatic Cancer

PURPOSE The prognosis for advanced pancreatic cancer remains poor. Gastrin acts as a growth factor for pancreatic cancer. We describe the first study of the antigastrin immunogen G17DT in pancreatic cancer. Our aims were to determine the antibody response, safety, tolerability, and preliminary evidence of efficacy of G17DT in advanced pancreatic cancer. PATIENTS AND METHODS Thirty patients with advanced pancreatic cancer were immunized with three doses of either 100 micro g or 250 micro g of G17DT. RESULTS In the whole group, 20 (67%) of 30 patients produced an antibody response. The 250- micro g dose resulted in a significantly greater response rate of 82% compared with 46% for the 100- micro g group (P =.018). The most significant side effects, seen in three patients, were local abscess and/or fever. The median survival for the whole group from the date of the first immunization was 187 days; median survival was 217 days for the antibody responders and 121 days for the antibody nonresponders. The difference in survival between the antibody responders and nonresponders was significant (P =.0023). CONCLUSION Patients with advanced pancreatic cancer are able to mount an adequate antibody response to G17DT. The 250- micro g dose is superior to the 100- micro g dose, and it appears to be generally well tolerated. Antibody responders demonstrate significantly greater survival than antibody nonresponders. Phase III studies are currently underway in order to determine efficacy.

Diagnosis of Duct Disruption and Assessment of Pancreatic Leak with Dynamic Secretin-Stimulated MR Cholangiopancreatography

OBJECTIVE The management of pancreatic duct disruption is complex and depends on several factors including the cause, morphology, and degree of disruption. ERCP can show duct disruption in as many as 75% of patients but is invasive and cannot detect disruption beyond an obstruction. We studied the role of secretin MR cholangiopancreatography in patients with suspected pancreatic duct disruption. CONCLUSION Secretin MR cholangiopancreatography is a safe, noninvasive test that can provide additional useful information about duct integrity and facilitate management.

A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.

Imaging of biliary strictures may suggest malignancy but cytology can provide a tissue diagnosis. The aim of this study is to compare the diagnostic value of brush cytology and bile cytology. Thirty two patients (20 males, 12 females, median age 66 years, range 31-84) with biliary strictures at endoscopic retrograde cholangio pancreatography (24) or percutaneous transhepatic cholangiography (8) had bile cytology and brush cytology. Brushings were taken using a modified Geenan cytology brush (6 Fr gauge, Wilson Cook) passed alongside a guide wire placed through the stricture. Bile was aspirated after insertion of an internal/external catheter or an endoprosthesis. Bile and brushings were examined by one experienced cytologist (AD) and was reported as positive or negative for malignant cells. Twenty nine patients had malignant strictures. Sixteen were confirmed by histology and 13 had malignancy suggested by clinical follow up. Three patients had resection of histologically benign strictures. The overall sensitivity of brush cytology (17 of 29 positive, 59%) was significantly greater than bile cytology (seven of 29 positive, 24%) (p < 0.01) as was the diagnostic accuracy (63 v 31%, p < 0.01). None of the patients had positive bile cytology with negative brush cytology. There were no procedure related complications and the average sampling time once the guide wire had been inserted was less than five minutes. It is concluded that brush cytology is more sensitive than bile cytology and with the technique described is safe and rapid.

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials

Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P=0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P=0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P=0.03), stomatitis (P<0.001) and hand– foot syndrome (P<0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.

Value of exfoliative cytology for investigating bile duct strictures.

The cause of a biliary tract stricture may be difficult to determine radiologically. Exfoliative biliary cytology was evaluated in 62 patients (median age 65 years, range 30-94) with biliary tract strictures presenting to the Hepatobiliary Unit between January 1984 and December 1989. Bile samples were taken during endoscopic retrograde cholangiopancreatography (ERCP) in 42 patients, percutaneous cholangiography in 14, and both in six. The site of stricturing was upper third of the bile duct in 43% (n = 27), middle third in 10% (n = six), and lower third in 47% (n = 29). Of the 47 patients with radiological appearances of a malignant stricture, 22 (47%) had histological confirmation by biopsy either under computed tomography guidance, at endoscopy, at operation, or at necropsy. Fourteen of the 47 patients had positive cytology (30%). In seven patients cytology alone established the presence of malignancy (15%) and in the other seven positive cytology was confirmed by histology. The addition of cytology to tissue biopsy therefore allowed malignancy to be confirmed in 29 of the 47 patients (62%). None of the 15 patients subsequently shown to have benign disease had positive cytology. Sensitivity of the technique was 30% and specificity 100%. Samples for exfoliative cytology are simple to obtain, the results are highly specific and should be a routine part of the investigation of biliary strictures.

Duct-to-duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis.

The biliary complications in patients undergoing biliary reconstruction by duct-to-duct (D-D) anastomosis or with a Roux-en-Y loop (RL) at the time of liver transplantation for primary sclerosing cholangitis (PSC, 16 D-D, 10 RL) or primary biliary cirrhosis (PBC, 31 D-D, 1 RL) were reviewed and compared. Patients were followed up for a mean period of 32 months. Extrahepatic biliary strictures occurred in 18.7%, 10% and 9.7% of DD-PSC, RL-PSC and DD-PBC patients, respectively, leaks in 6.2%, 20% and 6.4% DD-PSC, RL-PSC and DD-PBC patients, respectively (P=NS). Four intrahepatic biliary abnormalities developed in the PSC group. Duct-to-duct anastomosis did not significantly increase the risk of stricture formation or bile leaks in PSC patients compared to PBC patients. We conclude that duct-to-duct biliary reconstruction following liver transplantation for PSC is satisfactory unless the distal common bile duct is strictured.

Potential pitfalls in intraoperative parathyroid hormone measurements during parathyroid surgery

Background: The outcome of parathyroid surgery is often not clear for at least 24 h after the operation. A frozen section does not always distinguish between an adenoma and hyperplasia. Minimally invasive surgical techniques are being refined, so the need for perioperative assurance about the completeness of surgery has increased. The value of intraoperative parathyroid hormone (PTH) measurements in 26 surgical cases undergoing parathyroidectomy has been evaluated. Methods: Twenty-one patients were diagnosed as having primary hyperparathyroidism, including two patients with multiple endocrine neoplasia type I (MEN I). Five patients had tertiary hyperparathyroidism, including one patient with X-linked hypophosphataemia and four with renal hyperparathyroidism (RHPT). Blood samples were taken at the onset of surgery, at the time of tumour resection and at 5-min intervals following removal of the tumour. PTH was measured using a PTH Turbo assay on the DPC Immulite analyser. Results: Current practice suggests that the PTH concentration should fall to less than 50% of the pre-incision value or to less than 50% of the level at the time of tumour resection (time equals zero). PTH levels were therefore monitored at 5-min intervals following removal of the tumour. In most of the case studies PTH followed the suggested pattern, but not when further exploration was warranted to determine if another adenoma was present. In some cases the PTH levels fell by the appropriate margin to deem the procedure a success but at 10 min post-gland excision the PTH began to rise again. Further exploration was required to confirm the continued source of PTH. Conclusion: We recommend that intraoperative PTH measurements continue until at least 15 min post-gland removal in cases of suspected single-gland disease. A decline in PTH concentration to at least 50% of the pre-incision or time of gland resection levels should be observed. If the PTH remains elevated or rises again after an appropriate decrease in levels, then multigland disease or ectopic sources should be considered. Caution is recommended in interpreting intraoperative PTH measurements to ensure complete success of the surgical procedure.

A prospective randomized clinical trial of liver preservation using high-odium versus high-potassium lactobionate/raffinose solution

Abstract High‐odium as opposed to high‐potassium lactobionate/raffinose preservation solution offers potential advantages in improving the quality of liver storage by reducing potassium‐induced vasoconstriction and preventing hyperkalaemia on reperfusion. In our study we evaluated in a prospective trial (encompassing 40 consecutive cadaver donor hepatic retrievals and subsequent transplants) the efficacy of a high‐odium formulation versus the standard high‐potassium solution. Quality of preservation was assessed by clinical indices of liver function in the intraoperative and early postoperative phases, including measurements of requirements for blood and blood products and potassium, circulating liver enzymes and bilirubin. Frequencies of acute rejection episodes and primary non‐function were also recorded. No significant differences were evident in any of the measured parameters. Thus a sodium‐based solution can be used for hepatic preservation, advancing the possibility that it may be possible to develop a single storage solution for clinical multi‐organ donor operations.