Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial.

BACKGROUND: Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery. METHODS: ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete. FINDINGS: Between Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia. INTERPRETATION: Recruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma. FUNDING: Cancer Research UK.

A training tool to assess laparoscopic image navigation task performance in novice camera assistants.

BACKGROUND: A number of tools for assessing task performance of the laparoscopic camera assistant have been described, but few focus on the acquisition and assessment of the attainment of proficiency in novice laparoscopic camera assistants. Our aim was to develop a simulated objective assessment tool for a novice camera assistant. MATERIALS AND METHODS: A 10-cycle image navigation task tool was developed. This involved a series of 360° clockwise and anticlockwise rotation maneuvers of a 30° laparoscope along its shaft, focusing on a predefined geometric target on a 45° fixed slope in a laparoscopic box trainer. The tasks were to simultaneously maintain neutral horizon, optimum distance, and centering. Task accuracy and time to completion were assessed objectively at 3-s intervals on an unedited video recording. RESULTS: Twenty-nine novice medical students were assessed. Novices improved mean total error and task completion time (first versus fifth cycle, mean errors 15.4 versus 8.4, P = 0.048; mean task time 158.1 versus 92.9 s, P = 0.04). This improvement continued until the task cycle was completed (sixth versus 10th cycles, 7.9 versus 6.2, P = 0.01; 91.9 versus 76.6 s, P < 0.0001). There was a significant decrease in centering errors (5.2 versus 2.4, P = 0.001) and horizon (4.8 versus 2.3, P = 0.004), when comparing the first versus fifth task cycle. It took six cycles for optimum distance to achieve significance (5.4 versus 3.3, P = 0.023). CONCLUSIONS: Using our assessment tool, novices achieved an objective proficiency-gain curve for laparoscopic camera navigation tasks. There was improvement in errors related to maintaining horizon, optimum distance, and centering. Mean task completion time also decreased. This tool could be used as an additional mean of assessment and training in novice surgical trainees.

Pancreatic glucagonoma metastasising to the right ovary five years after initial surgery: a case report.

CONTEXT: Glucagonomas of the pancreas are neuroendocrine tumours (NETs) that arise from well-differentiated neuroendocrine cells within the pancreatic islets. They are considered to be aggressive NETs and often have metastases at initial presentation. In contrast localised glucagonoma without metastatic spread may have prolonged disease free survival with radical resectional surgery. CASE REPORT: The authors present a case of a glucagonoma that initially presented with classical necrolytic migratory erythema and a large solitary mass in the body and tail of the pancreas that was surgically resected. Five years after surgery the patient presented with increased serum glucagon levels and a mass in the right ovary. Pathology of the resected ovary after oophorectomy identified this as an isolated metastatic glucagonoma. CONCLUSION: Glucagonoma is a rare pancreatic NET that has significant malignant potential. This is the first case of a pancreatic glucagonoma metastasising to the ovary 5 years after radical distal pancreatosplenectomy.

Totally laparoscopic strategies for the management of colorectal cancer with synchronous liver metastasis.

INTRODUCTION: Laparoscopy is an accepted treatment for colorectal cancer and liver metastases, but there is no consensus for its use in the management of synchronous liver metastases (SCRLM). The purpose of this study was to evaluate totally laparoscopic strategies in the management of colorectal cancer with synchronous liver metastases. METHODS: Patients presenting to Ninewells Hospital between July 2007 and August 2010, with adenocarcinoma of the colon and rectum with synchronous liver metastases were considered. Patients underwent simultaneous laparoscopic liver and colon cancer resection, a staged laparoscopic resection of SCRLM and colon cancer, or simultaneous colon resection and radiofrequency ablation (RFA) of SCRLM. Primary endpoints were in-hospital morbidity and mortality, total hospital stay, intraoperative blood loss, duration of surgery, and resection margin status. RESULTS: Twenty-eight patients presented with synchronous colorectal liver metastases. Thirteen patients underwent a simultaneous laparoscopic liver and colon resection (median operating time, 370 (range, 190-540) min; median hospital stay, 7 (range, 3-54) days), seven patients had a staged laparoscopic resection of SCRLM and primary colon cancer (median operating time, 530 (range, 360-980) min; median hospital stay 14, (range, 6-51) days), and eight patients underwent laparoscopic colon resection and RFA of SCRLM (median operating time, 310 (range, 240-425) min; median hospital stay, 8 (range, 6-13) days). There were no conversions to an open procedure. Overall in-hospital morbidity and mortality was 28 and 0 % respectively. An R0 resection margin was achieved in 91 % of the resection group. At a median follow-up of 26 (range, 18-55) months, 19 (90 %) patients remain disease-free. CONCLUSIONS: Totally laparoscopic strategies for the radical treatment of stage IV colorectal cancer are feasible with low morbidity and favorable outcomes. A laparoscopic approach for the simultaneous management of SCRLM and primary colon cancer is associated with reduced surgical access trauma, postoperative morbidity, and hospital stay with no compromise in short-term oncological outcome.

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

CONTEXT: There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. OBJECTIVES: To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. DESIGN: All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. RESULTS: Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). CONCLUSION: A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Impact of methicillin-resistant Staphylococcus Aureus (MRSA) infection on patient outcome after pancreatoduodenectomy (PD)--a cause for concern?

OBJECTIVES: This study evaluated the impact of methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired infection on postoperative complications and patient outcome after pancreatoduodenectomy (PD). METHODS: Seventy-nine patients who underwent PD were monitored for hospital-acquired MRSA. The patients were grouped as (1) no MRSA infection, (2) skin colonization with MRSA, and (3) systemic MRSA infection. RESULTS: Forty (51%) of the 79 patients were MRSA positive during hospital admission. Fourteen of the 40 patients swabbed for MRSA were found positive (skin colonization), and 26 patients (33%) developed systemic MRSA infection after PD. The sites of MRSA infection included (1) abdominal drain fluid (16/26; 42%), (2) sputum (4/26; 15%), (3) blood cultures (2/26; 8%), and (4) combination of sites (9/26; 35%). The patients with systemic MRSA infection had a longer postoperative stay (31 vs 22 days; P = 0.005) and increased incidence of chest infections compared with MRSA-negative patients (14 vs 4; P = 0.02). Four of the 16 patients with MRSA-positive drain fluid had a postpancreatectomy hemorrhage compared with 3 of the 63 patients with no MRSA infection in drain fluid (P = 0.02). CONCLUSION: Of the 79 patients admitted for PD, 51% became colonized with MRSA infection. Systemic hospital-acquired MRSA infection in 33% was associated with prolonged postoperative stay, increased wound and chest infections, and increased risk of postoperative hemorrhage.

Late post pancreatectomy haemorrhage. Risk factors and modern management.

CONTEXT: Current management of late post-pancreatectomy haemorrhage in a university hospital. OBJECTIVE: Haemorrhage after pancreaticoduodenectomy is a serious complication. We report on risk factors and outcome following management by radiological intervention. SETTING: Tertiary care centre in Scotland. SUBJECTS: Sixty-seven consecutive patients who underwent pancreaticoduodenectomy. METHODS: All pancreaticoduodenectomies over a 3-year period were reviewed. International Study Group on Pancreatic Surgery (ISGPS) definition of post-pancreatectomy haemorrhage was used. MAIN OUTCOME MEASURES: Endpoints were incidence of haemorrhage, pancreaticojejunal anastomosis leak, methicillin-resistant Staphylococcus aureus (MRSA) infection and mortality. RESULTS: Seven patients (10.4%) developed post-pancreatectomy haemorrhage out of 67 pancreaticoduodenectomies. Median age was 71 years. All post-pancreatectomy haemorrhage were late onset (median 23 days; range: 3-35 days), extraluminal and ISGPS grade C. Post-pancreatectomy haemorrhage arose from hepatic artery (n=4), superior mesenteric artery (n=1), jejunal artery (n=1), and splenic artery (n=1). Angiographic treatment was successful in all patients by embolisation (n=5) or stent grafting (n=2). Pancreatic fistula rate was similar in post-pancreatectomy haemorrhage and "no-haemorrhage" groups (57.1% vs. 40.0%; P=0.440); MRSA infection was significantly higher in post-pancreatectomy haemorrhage group (57.1% vs. 16.7%; P=0.030). Mortality from post-pancreatectomy haemorrhage despite successful haemostasis was 42.9%. Univariate and multivariate analysis identified MRSA infection as a risk factor for post-pancreatectomy haemorrhage. CONCLUSION: CT angiogram followed by conventional catheter angiography is effective for treatment of late extraluminal post-pancreatectomy haemorrhage. MRSA infection in the abdominal drain fluid increases its risk and therefore aggressive treatment of MRSA and high index of suspicion are indicated.

Management guidelines for gallstone pancreatitis. Are the targets achievable?

CONTEXT: Current management of gallstone pancreatitis in a university hospital. OBJECTIVE: Comparison of current management of gallstone pancreatitis with recommendations in national guidelines. SETTING: Tertiary care centre in Scotland. SUBJECTS: One-hundred consecutive patients admitted with gallstone pancreatitis. METHODS: All patients that presented with gallstone pancreatitis over a 4-year period were audited retrospectively. Data were collated for radiological diagnosis within 48 hours, ERCP within 72 hours, CT at 6-10 days, and use of high-dependency or intensive therapy units in severe gallstone pancreatitis, and definitive treatment of gallstone pancreatitis within 2 weeks as recommended in national guidelines. RESULTS: Forty-six patients had severe gallstone pancreatitis and 54 patients mild pancreatitis. Etiology was established within 48 hours in 92 patients. Six (13.0%) out of the patients with severe gallstone pancreatitis were managed in a high dependency unit. Fifteen (32.6%) patients with severe gallstone pancreatitis underwent CT within 6-10 days of admission. Four (8.7%) of the 46 patients with severe gallstone pancreatitis had urgent ERCP (less than 72 hours). Overall 22/100 patients unsuitable for surgery underwent endoscopic sphincterotomy as definitive treatment. Seventy-eight patients had surgery, with 40 (51.3%) of these patients undergoing an index admission cholecystectomy, and 38 (48.7%) patients were discharged for interval cholecystectomy. Overall 81 patients with gallstone pancreatitis had definitive therapy during the index to same admission (cholecystectomy or sphincterotomy). Two (5.3%) patients were readmitted whilst awaiting interval cholecystectomy: one with acute cholecystitis and one with acute pancreatitis. There were no mortalities in this cohort. CONCLUSION: This study has highlighted difficulties in implementation of national guidelines, as the use of critical care, timing of ERCP and CT, and definitive treatment prior to discharge did not concur with national targets for gallstone pancreatitis.

Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma.

BACKGROUND: The majority of patients with hilar cholangiocarcinoma have irresectable disease and require palliation with biliary stenting to alleviate symptoms and prevent biliary sepsis. Chemotherapy and radiotherapy have proved ineffective, but recent studies suggest photodynamic therapy (PDT) may improve the outlook for these patients. This prospective clinical cohort study has evaluated the efficacy of radical curative surgery, standard palliative therapy (stent +/- chemotherapy) and a novel palliative therapy (stent +/- Photofrin-PDT) in 50 consecutive patients treated for hilar cholangiocarcinoma over a 5-year period. METHODS: Between January 2002 and December 2006, 50 patients with hilar cholangiocarcinoma were evaluated for treatment. Ten patients were considered suitable for curative resection (Cohort 1). Forty patients with irresectable disease were stratified into Cohort 2 - Stent +/- chemotherapy (n= 17); and Cohort 3 - Stent +/- PDT (n= 23). Prospective follow-up in all patients and data collected for morbidity, mortality and overall patient survival. RESULTS: The median age was 68 years [range 44-83]. Positive cytology/histology was obtained in 28/50 (56%). One death in Cohort 1 occurred at 145 days after surgical resection. No treatment related-deaths occurred in Cohort 2 or 3, chemotherapy-induced morbidity in three patients in cohort 2, PDT-induced morbidity in 11 patients in cohort 3. Actual 1-year survival was 80%, 12% and 75% in Cohorts 1, 2 and 3, respectively. Mean survival after resection was 1278 days (median survival not reached). Mean and median survival was 173 and 169 days, respectively, in Cohort 2; and 512 and 425 days in Cohort 3. Patient survival was significantly longer in cohorts 1 and 3 (P < 0.0001; Log rank test). CONCLUSION: This prospective clinical cohort study has demonstrated that radical surgery and palliative Photofrin-PDT are associated with an increased survival in patients with hilar cholangiocarcinoma.

Laparoscopic versus open liver segmentectomy: prospective, case-matched, intention-to-treat analysis of clinical outcomes and cost effectiveness.

INTRODUCTION: Reduction in hospital stay, blood loss, postoperative pain and complications are common findings after laparoscopic liver resection, suggesting that the laparoscopic approach may be a suitable alternative to open surgery. Some concerns have been raised regarding cost effectiveness of this procedure and potential implications of its large-scale application. Our aim has been to determine cost effectiveness of laparoscopic liver surgery by a case-matched, case-control, intention-to-treat analysis of its costs and short-term clinical outcomes compared with open surgery. METHODS: Laparoscopic liver segmentectomies and bisegmentectomies performed at Ninewells Hospital and Medical School between 2005 and 2007 were considered. Resections involving more than two Couinaud segments, or involving any synchronous procedure, were excluded. An operation-magnitude-matched control group was identified amongst open liver resections performed between 2004 and 2007. Hospital costs were obtained from the Scottish Health Service Costs Book (ISD Scotland) and average national costs were calculated. Cost of theatre time, disposable surgical devices, hospital stay, and high-dependency unit (HDU) and intensive care unit (ICU) usage were the main endpoints for comparison. Secondary endpoints were morbidity and mortality. Statistical analysis was performed with Student's t-test, chi(2) and Fisher exact test as most appropriate. RESULTS: Twenty-five laparoscopic liver resections were considered, including atypical resection, segmentectomy and bisegmentectomy, and they were compared to 25 matching open resections. The two groups were homogeneous by age, sex, coexistent morbidity, magnitude of resection, prevalence of liver cirrhosis and indications. Operative time (p < 0.03), blood loss (p < 0.0001), Pringle manoeuvre (p < 0.03), hospital stay (p < 0.003) and postoperative complications (p < 0.002) were significantly reduced in the laparoscopic group. Overall hospital cost was significantly lower in the laparoscopic group by an average of 2,571 pounds sterling (p < 0.04). CONCLUSIONS: Laparoscopic liver segmentectomy and bisegmentectomy are feasible, safe and cost effective compared to similar open resections. Large-scale application of laparoscopic liver surgery could translate into significant savings to hospitals and health care programmes.

Endoscopic sphincterotomy and interval cholecystectomy are reasonable alternatives to index cholecystectomy in severe acute gallstone pancreatitis (GSP).

BACKGROUND: UK guidelines for gallstone pancreatitis (GSP) advocate definitive treatment during the index admission, or within 2 weeks of discharge. However, this target may not always be achievable. This study reviewed current management of GSP in a university hospital and evaluated the risk associated with interval cholecystectomy. METHODS: All patients that presented with GSP over a 4-year period (2002-2005) were stratified for disease severity (APACHE II). Patient demographics, time to definitive therapy [index cholecystectomy; endoscopic sphincterotomy (ES); Interval cholecystectomy], and readmission rates were analysed retrospectively. RESULTS: 100 patients admitted with GSP. Disease severity was mild in 54 patients and severe in 46 patients. Twenty-two patients unsuitable for surgery underwent ES as definitive treatment with no readmissions. Seventy-eight patients underwent cholecystectomy, of which 40 (58%) had an index cholecystectomy, and 38 (42%) an interval cholecystectomy. Only 10 patients with severe GSP had an index cholecystectomy, whilst 30 were readmitted for Interval cholecystectomy (p = 0.04). The median APACHE score was 4 [standard deviation (SD) 3.8] for index cholecystectomy and 8 (SD 2.6) for Interval cholecystectomy (p < 0.05). Median time (range) to surgery was 7.5 (2-30) days for index cholecystectomy and 63 (13-210) days for Interval cholecystectomy. Fifty percent (19/38) of patients with GSP had ES prior to discharge for interval cholecystectomy. Two (5%) patients were readmitted: with acute cholecystitis (n = 1) and acute pancreatitis (n = 1) , whilst awaiting interval cholecystectomy. No mortality was noted in the Index or Interval group. CONCLUSIONS: This study demonstrates that overall 62% (22 endoscopic sphincterotomy and 40 index cholecystectomy) of patients with GSP have definitive therapy during the Index admission. However, surgery was deferred in the majority (n = 30) of patients with severe GSP, and 19/30 underwent ES prior to discharge. ES and interval cholecystectomy in severe GSP is associated with minimal morbidity and readmission rates, and is considered a reasonable alternative to an index cholecystectomy in patients with severe GSP.

CA 19-9 and survival in advanced and unresectable pancreatic adenocarcinoma and cholangiocarcinoma.

BACKGROUND: The CA 19-9 tumour marker is increasingly used to monitor response to therapy in patients with pancreatic adenocarcinoma. Serum CA 19-9 levels have also been shown to correlate with survival. However, their role in cholangiocarcinoma is less clear. AIM OF STUDY: To assess the utility of CA 19-9 levels in the management of patients with advanced pancreatic adenocarcinoma or cholangiocarcinoma in routine clinical practice is the aim of the study. METHODS: A retrospective analysis of CA 19-9 values and survival was performed in 26 patients with pancreatic adenocarcinoma receiving gemcitabine and in 18 patients with cholangiocarcinoma. RESULTS: Patients with advanced pancreatic adenocarcinoma receiving gemcitabine who experienced a decrease of > or = 20% in CA 19-9 concentration had a median survival of 13.9+ months (range 4.2-23.5) compared to 7.6+ months (range 4.0-14.7) in those without such a change (p = 0.0109). In patients with advanced cholangiocarcinoma, the median survival was longest in those with a baseline CA 19-9 level of less than 1,000 U/ml; 11.8 months (range 1.0-41.4) vs 6.2 months (range 3.1-9.4; p = 0.0075). CONCLUSIONS: The CA 19-9 concentration has a valuable role in predicting outcome in patients with pancreatic adenocarcinoma and cholangiocarcinoma. It is helpful in guiding therapy and should be used accordingly in oncology practice.

Liver cell adenoma and liver cell adenomatosis.

During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection.

Treatment of grade III anal intraepithelial neoplasia with photodynamic therapy: report of a case.

PURPOSE: We report the use of photodynamic therapy to treat a 53-year-old female with Grade III anal intraepithelial neoplasia. METHODS: Topical 5-aminolevulinic acid cream was applied to the affected area five hours before light treatment. The distribution of 5-aminolevulinic acid-induced protoporphyrin IX was identified by its characteristic red fluorescence. The lesion was treated by illumination with a 630-nm red laser light that used a total energy of 125 J/cm2 for approximately 17 minutes. RESULTS: Complete symptomatic relief was achieved after the first photodynamic therapy session, and macroscopic and microscopic ablation of dysplasia was achieved after a second session of photodynamic therapy. Healing was excellent, with no residual scarring or functional loss. CONCLUSION: Photodynamic therapy offers a simple, noninvasive method for treatment of anal intraepithelial neoplasia.