Alice Gillams

Photodynamic therapy for cancer of the pancreas.

Background: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. Aims: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. Patients: Sixteen patients with inoperable adenocarcinomas (2.5–6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. Methods: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. Results: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4–30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. Conclusions: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Autoimmune Pancreatitis: Clinical and Radiological Features and Objective Response to Steroid Therapy in a UK Series

OBJECTIVE:Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression.METHODS:Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted.RESULTS:Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 μmol/L to 11 μmol/L (P = 0.001), and ALT from 97 IU/L to 39 IU/L (P = 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well.CONCLUSIONS:Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.

Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer.

Background:Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.Methods:Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg−1 verteporfin. After 60–90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.Results:In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm3 at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple’s pancreaticoduodenectomy.Conclusions:Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.

Prospective comparison of secretin‐stimulated magnetic resonance cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi dysfunction types II and III

Background: In sphincter of Oddi dysfunction (SOD), sphincter of Oddi manometry (SOM) predicts the response to sphincterotomy, but is invasive and associated with complications. Aim: To evaluate the role of secretin-stimulated magnetic resonance cholangiopancreatography (ss-MRCP) in predicting the results of SOM in patients with suspected type II or III SOD. Methods: MRCP was performed at baseline and at 1, 3, 5 and 7 min after intravenous secretin. SOD was diagnosed when the mean basal sphincter pressure at SOM was >40 mm Hg. Long-term outcome after SOM, with or without endoscopic sphincterotomy, was assessed using an 11-point (0–10) Likert scale. Results: Of 47 patients (male/female 9/38; mean age 46 years; range 27–69 years) referred for SOM, 27 (57%) had SOD and underwent biliary and/or pancreatic sphincterotomy. ss-MRCP was abnormal in 10/16 (63%) type II and 0/11 type III SOD cases. The diagnostic accuracy of ss-MRCP for SOD types II and III was 73% and 46%, respectively. During a mean follow-up of 31.6 (range 17–44) months, patients with normal SOM and SOD type II experienced a significant reduction in symptoms (mean Likert score 8 vs 4; p = 0.03, and 9 vs 1.6; p = 0.0002, respectively), whereas in patients with SOD type III, there was no improvement in pain scores. All patients with SOD and an abnormal ss-MRCP (n = 12) reported long-term symptom improvement (mean Likert score 9.2 v 1.2, p<0.001). Conclusions: ss-MRCP is insensitive in predicting abnormal manometry in patients with suspected type III SOD, but is useful in selecting patients with suspected SOD II who are most likely to benefit from endotherapy.

Prospective study comparing multislice CT colonography with colonoscopy in the detection of colorectal cancer and polyps.

AbstractPURPOSE: Multislice CT colonography is an alternative to colonoscopy. The purpose of this study was to compare multislice CT colonography with colonoscopy in the detection of colorectal polyps and cancers. METHODS: Between June 2000 and December 2001, 45 males and 35 females (median age, 68 (29–83) years) with symptoms of colorectal disease were studied prospectively. All patients underwent multislice CT colonography and colonoscopy, and the findings were compared. RESULTS: Colonoscopy was incomplete in 18 (22 percent) patients because of obstructing lesions or technical difficulty, and multislice CT colonography was unsuccessful in 4 (5 percent) because of fecal residue. Colonoscopy was normal in 26 patients and detected 29 colorectal cancers and 33 polyps in 35 patients, diverticulosis in 16 patients, and colitis in 3 patients. Multislice CT colonography identified 28 of 29 colorectal cancers with one false negative and one false positive (sensitivity, 97 percent; specificity, 98 percent; positive predictive value, 96 percent; negative predictive value, 98 percent). Multislice CT colonography identified all 12 polyps measuring ≥10 mm in diameter (sensitivity, 100 percent), 5 of 6 measuring 6 to 9 mm in diameter (sensitivity, 83 percent), 8 of 15 polyps ≤5 mm (sensitivity, 53 percent), and false-positive for 8 polyps. The overall sensitivity was 74 percent and specificity 96 percent. The positive predictive value for polyps was 88 percent, and the negative predictive value was 90 percent. Multislice CT colonography also detected 5 of 16 patients with diverticulosis (sensitivity, 31 percent; specificity, 98 percent) and colitis in 2 of 3 patients (sensitivity, 67 percent; specificity, 100 percent). In ten (13 percent) patients, extracolonic findings on multislice CT colonography altered management and included five patients with colorectal liver metastases. In 15 (19 percent) patients, there were incidental findings that did not demand further investigation. CONCLUSIONS: The results from this study indicate that the efficacy of multislice CT colonography in the detection of colorectal cancers and polyps ≥6 mm is similar to colonoscopy. Multislice CT colonography allows clinical staging of colorectal cancers, outlines the whole length of the colon in obstructing carcinoma when colonoscopy fails, and can identify extracolonic causes of abdominal symptoms.

Percutaneous cholecystolithotomy: is gall stone recurrence inevitable?

Using radiological interventional techniques the gall bladder can be cleared of stones with a high success rate. As with any treatment option that leaves the gall bladder in situ there is an accompanying risk of stone recurrence, which is currently unknown for the radiological method. One hundred patients were studied prospectively to determine the recurrence rate of stones and clinical outcome after successful percutaneous cholecystolithotomy. Follow up included both clinical assessment and ultrasound examination at 3, 6, and 12 months and then annual intervals thereafter. The overall stone recurrence rate was 31% at a mean follow up of 26 months (range, 3-50 months). By actuarial life table analysis, the cumulative proportion of gall stone recurrence was 7, 19, 28, 35, and 44% at 6, 12, 24, 36, and 48 months respectively. Of the 31 patients with recurrent stones; 17 remain asymptomatic, seven have experienced biliary colic, two abdominal pain, three non-specific upper gastrointestinal symptoms, and two jaundice secondary to common duct stones. Thirteen of the stone free patients have remained symptomatic; six with abdominal pain and seven with nonspecific upper gastrointestinal symptoms. Eight patients have subsequently had a cholecystectomy. No significant difference was found between the sex of the patient or the number of stones before treatment and the stone recurrence rates. The cumulative stone recurrence rate was significantly less in the 56 patients who received adjuvant chemolitholysis (p < 0.05). These data show that stone recurrence after successful percutaneous cholecystolithotomy occurs in the minority, and is usually asymptomatic. It is concluded that the technique remains justified in the management of selected patients with gall stones.

Photodynamic therapy of pancreatic cancer and elastic scattering spectroscopy of the duodenal mucosa for the detection of pancreaticobiliary malignancy

The diagnosis and treatment of pancreaticobiliary malignancy is of major interest to our group. Building on prior work, we undertook a phase I study of verteporfin photodynamic therapy in patients with locally advanced, unresectable, pancreatic cancer. We also initiated an optical diagnostic study using elastic scattering spectroscopy (ESS) of the normal-appearing periampullary duodenal mucosa in vivo to investigate the hypothesis of a field effect in pancreaticobiliary malignancy. In a phase I dose escalation study, patients were treated with interstitial verteporfin PDT via a single fibre, to determine its general safety profile and the optimum treatment parameters needed to achieve effective and safe necrosis of tumour, With increasing light doses, there was a linear increase in the extent of tumour necrosis around the fibre, without serious adverse events. Follow-on studies using multiple fibres are planned. In 30 patients with benign or malignant pancreaticobiliary disease undergoing clinically-indicated endoscopy, ESS spectra were collected from the normal-appearing duodenum and antrum and a diagnostic algorithm generated by principle component and linear discriminant analysis. Pooled data from duodenal sites distal to the ampulla gave a sensitivity of 86% and a specificity of 72% (82% AUC) for the detection of malignancy, whereas those from the periampullary region had a sensitivity of 77% and a specificity of 61% (72% AUC); antral measurements were not able to discriminate with such accuracy. These early results suggest that ESS of the duodenal mucosa could represent a novel minimally invasive diagnostic test for pancreaticobiliary malignancy.

The percutaneous rotary lithotrite: a new approach to the treatment of symptomatic cholecystolithiasis.

This report evaluates the use of a new device for destruction of gall stones, the Kensey-Nash Lithotrite (Baxter Corporation, California, USA). The principle of the instrument is that of a liquidiser with an impeller that emulsifies stones. Twenty five patients were treated; 13 patients were considered unfit for conventional treatment (complex group) and 12 elected to have the procedure (non-complex group). In the complex group nine patients were treated under local anaesthesia. Only six of the 13 patients had a clear gall bladder at the end of the first procedure, but after further treatments that included cholecystoscopy, endoscopic sphincterotomy, and percutaneous cholecystolithotomy 11 patients had a gall bladder free of stones. The morbidity was high, mainly due to pain and bile leaks, causing prolonged stays in hospital (median 18 days). In the non-complex group six patients had the procedure performed under local anaesthesia. Ten patients had a successful clearance of the gall bladder, and the remaining two patients had the stones removed at cholecystoscopy. Despite good clearance, the morbidity was high, with eight emergency admissions on account of complications and a prolonged duration of stay (median 13 days). In conclusion the technique is effective, but the morbidity is high. Further development is required if this technique is to be included in the alternative treatments for the management of gall stones.

'Nipped in the Budd': hepatic venous outflow obstruction in evolution

Hepatic venous thrombosis (Budd-Chiari) in evolution is a rare phenomenon and carries a high morbidity and mortality. We describe the case of a 39-year-old Bangladeshi lady who presented with severe abdominal pain secondary to a perforated duodenal ulcer and during her hospital admission developed an asymptomatic Budd-Chiari syndrome (BCS). Our report highlights the important role of an inflammatory focus, and how this process with an associated reactive thrombocytosis may act as a trigger for the development of BCS in an individual with predisposing risk factors. Our patient had been on the contraceptive pill, and was homozygous for the C677T mutation of 5,10-methylenetetrahydrofolate reductase, which results in hyperhomocysteinaemia. These pro-thrombotic risk factors were compounded by the thrombogenic potential of subsequent laparoscopic surgery, and resulted in an evolving thrombus that progressed into the inferior vena cava causing hepatic infarction. A particular feature of this case was the radiological demonstration of complete regression of the thrombus and the hepatic parenchymal changes, upon resolution of the inflammation and normalization of the platelet count. These changes occurred with oral anticoagulation as the only treatment modality, since our patient declined systemic thrombolysis. The demonstration of complete radiological resolution raises the question of how long one should continue oral anticoagulants and, indeed, whether in some instances a conservative approach may be the best management strategy for evolving BCS.