C.H.J. van Eijck

The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer

OBJECTIVES:Approximately 10–15% of all pancreatic cancers (PCs) may be hereditary in origin. We investigated the use of endoscopic ultrasonography (EUS) for the screening of individuals at high risk for developing PC. In this paper the results of first-time screening with EUS are presented.METHODS:Those eligible for screening in this study were first-degree family members of affected individuals from familial pancreatic cancer (FPC) families, mutation carriers of PC-prone hereditary syndromes, individuals with Peutz–Jeghers syndrome, and mutation carriers of other PC-prone hereditary syndromes with clustering (≥2 cases per family) of PC. All individuals were asymptomatic and had not undergone EUS before.RESULTS:Forty-four individuals (M/F 18/26), aged 32–75 years underwent screening with EUS. Thirteen were from families with familial atypical multiple-mole melanoma (FAMMM), 21 with FPC, 3 individuals were diagnosed with hereditary pancreatitis, 2 were Peutz–Jeghers patients, 3 were BRCA1 and 2 were BRCA2 mutation carriers with familial clustering of PC, and 1 individual had a p53 mutation. Three (6.8%) patients had an asymptomatic mass lesion (12, 27, and 50 mm) in the body (n=2) or tail of the pancreas. All lesions were completely resected. Pathology showed moderately differentiated adenocarcinomas with N1 disease in the two patients with the largest lesions. EUS showed branch-type intraductal papillary mucinous neoplasia (IPMN) in seven individuals.CONCLUSIONS:Screening of individuals at a high risk for PC with EUS is feasible and safe. The incidence of clinically relevant findings at first screening is high with asymptomatic cancer in 7% and premalignant IPMN-like lesions in 16% in our series. Whether screening improves survival remains to be determined, as does the optimal screening interval with EUS.

Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality

The impact of nationwide centralization of pancreaticoduodenectomy (PD) on mortality is largely unknown. The aim of this study was to analyse changes in hospital volumes and in‐hospital mortality after PD in the Netherlands between 2004 and 2009.

Somatostatin-receptor scintigraphy in primary breast cancer

Somatostatin-receptor (SS-R) scintigraphy successfully shows primary cancers and distant metastases in most patients with carcinoids, islet cells tumours, and paragangliomas. Previous in-vitro studies indicated that somatostatin receptors are present in human breast cancers. We report positive scintigraphy with [111In-DTPA-D-Phe1]-octreotide in 39 of 52 primary breast cancers (75%). Parallel in-vitro autoradiography with [125I-Tyr3]-octreotide of 30 of these showed a corresponding somatostatin-receptor status in 28. Significantly more invasive ductal cancers could be shown than invasive lobular carcinomas (85% vs 56%; p < 0.05). Also the number of T2 cancers which were shown was higher than T1 (86% vs 61%; p < 0.05). Imaging of the axillae showed non-palpable cancer-containing lymph nodes in 4 of 13 patients with subsequently histologically-proven metastases. In the follow-up after a mean of 2.5 yr, SS-R scintigraphy in 28 of the 37 patients with an originally SS-R-positive cancer, was positive in the 2 patients with clinically-recognised metastases, as well as in 6 of the remaining 26 patients who were symptom-free. Raised carcinoembryonic antigen (CEA) and CA 15-3 values were observed in only 2 and 1, respectively, of these patients. Most primary breast cancers can be shown by SS-R scintigraphy, especially invasive ductal cancers. This technique may be of value in selecting patients for clinical trials with somatostatin analogues or other medical treatments. Furthermore, SS-R scintigraphy is more sensitive than measurements of the usual serum cancer markers for detecting recurrences of SS-R-positive breast cancer.

Systematic review and meta-analysis of the association between diabetes mellitus and incidence and mortality in breast and colorectal cancer

Increasing evidence suggests that diabetes mellitus (DM) is associated with increased cancer incidence and mortality. Several mechanisms involved in diabetes, such as promotion of cell proliferation and decreased apoptosis, may foster carcinogenesis. This study investigated the association between DM and cancer incidence and cancer‐specific mortality in patients with breast and colorectal carcinoma.

Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma

BACKGROUND Surgery on pheochromocytoma carries a risk for hemodynamic (HD) instability. The aim of this study was to identify preoperative risk factors for intraoperative HD instability. In addition, efficacy of pretreatment with the alpha-adrenergic receptor (alpha) antagonists phenoxybenzamine (PXB) and doxazosin (DOX) was compared with respect to reduction of intraoperative HD instability. METHODS Seventy-three patients operated in Erasmus Medical Center between 1995 and 2007 were included. Parameters studied were catecholamine type and concentration, tumor diameter, mean arterial pressure (MAP) before and after (MAP(alpha)) pretreatment with alpha-antagonist, postural fall in blood pressure (BP) after pretreatment, type of alpha-blockade, type of operation, and presence of a familial polytumor syndrome. HD instability was assessed by measuring the number and time period MAP was below 60 mm Hg and systolic BP (SBP) was above 160 mm Hg. RESULTS A correlation was found between the intraoperative time periods of SBP above 160 mm Hg and plasma norepinephrine levels (r = 0.23; P < 0.05), tumor diameter (r = 0.36; P < 0.01), and postural BP fall (r = 0.30; P < 0.05). MAP at presentation and after alpha-blockade above 100 mm Hg (BP, 130/85 mm Hg) was related to more and longer episodes with a SBP above 160 mm Hg (P < 0.01). Type of operation or alpha-blockade and presence of a familial polytumor syndrome were not related to intraoperative HD instability. Postoperative MAP was lower in the DOX group than in the PXB group (P < 0.05). CONCLUSION Risk factors for HD instability during surgery for pheochromocytoma include a high plasma NE concentration, larger tumor size, more profound postural BP fall after alpha-blockade, and a MAP above 100 mm Hg (130/85 mm Hg). Efficacy for preventing HD instability was identical for PXB and DOX.

Successful endoscopic treatment of chronic groin pain in athletes.

BackgroundChronic groin pain, especially in professional sportsmen, is a difficult clinical problem.MethodsFrom January 1999 to August 2005, 55 professional and semiprofessional sportsmen (53 males; mean age, 25 ± 4.5 years; range, 17–36 years) with undiagnosed chronic groin pain were followed prospectively. All the patients underwent an endoscopic total extraperitoneal (TEP) mesh placement.ResultsIncipient hernia was diagnosed in the study athletes: 15 on the right side (27%), 12 on the left side (22%), and 9 bilaterally (16%). In 20 patients (36%), an inguinal hernia was found: 3 direct inguinal hernias (5%) and 17 indirect hernias (31%). All the athletes returned to their normal sports level within 3 months after the operation.ConclusionsA TEP repair must be proposed to patients with prolonged groin pain unresponsive to conservative treatment. If no clear pathology is identified, reinforcement of the wall using a mesh offers good clinical results for athletes with idiopathic groin pain.

Survival after surgical management of pancreatic adenocarcinoma: does curative and radical surgery truly exist?

Surgery for pancreatic cancer offers a low success rate but it provides the only likelihood of cure. Modern series show that, in experienced hands, the standard Whipple procedure is associated with a 5-year survival of 10%–20%, with a perioperative mortality rate of less than 5%. Most patients, however, will develop recurrent disease within 2 years after curative treatment. This occurs, usually, either at the site of resection or in the liver. This suggests the presence of micrometastases at the time of operation. Negative lymph nodes are the strongest predictor for long-term survival. Other predictors for a favourable outcome are tumour size, radical surgery and a histopathologically well-differentiated tumour. Adjuvant therapy has, so far, shown only modest results, with 5FU chemotherapy, to date, the only proven agent able to increase survival. Nowadays, the choice of therapy should be based on histopathological assessment of the tumour. Knowledge of the molecular basis of pancreatic cancer has led to various discoveries concerning its character and type. Well-known examples of genetic mutations in adenocarcinoma of the pancreas are k-ras, p53, p16, DPC4. Use of molecular diagnostics and markers in the assessment of tumour biology may, in future, reveal important subtypes of this type of tumour and may possibly predict the response to adjuvant therapy. Defining the subtypes of pancreatic cancer will, hopefully, lead to target-specific, less toxic and finally more effective therapies. Long-term survival is observed in only a very small group of patients, contradicting the published actuarial survival rates of 10%–45%. Assessment of clinical benefit from surgery and adjuvant therapy should, therefore, not only be based on actuarial survival but also on progression-free survival, actual survival, median survival and quality of life (QOL) indicators. Survival in surgical series is usually calculated by actuarial methods. If there is no information on the total number of patients and the number of actual survivors, and no clear definition of the subset of patients, actuarial survival curves can prove to be misleading. Proper assessment of QOL after surgery and adjuvant therapy is of the utmost importance, as improvements in survival rates have, so far, proved to be disappointing.

Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum.

In this experimental study, the effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum was investigated. A reproducible in vitro assay was developed to study the adhesion of CC531 colon carcinoma cells to an autologous monolayer of rat mesothelial cells. Tumour cell adhesion to mesothelium pre‐incubated with interleukin‐1β (IL‐1β) and epidermal growth factor (EGF) resulted in at least 60% more tumour cell adhesion at maximal stimulation (p≤0.001). Transforming growth factor‐β (TGF‐β) pre‐incubation resulted in minor, though significant stimulation of cell adhesion (maximal 16%, p<0.05). The effect of IL‐1β was time‐ and dose‐dependent. No mesothelial cell proliferation took place after pretreatment with IL‐1β, indicating that enhanced adhesion was not based on an increase in the number of mesothelial cells. Pretreatment with EGF stimulated mesothelial cell growth as measured by DNA analysis. This effect on cell growth and adhesion was dose‐dependent. Additional blocking experiments with anti‐IL‐1β resulted in statistically significant inhibition of IL‐1β‐stimulated tumour cell adhesion (p≤0.01), demonstrating the specificity of this effect. Interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α), IL‐6, and insulin‐like growth factor (IGF‐I) pre‐incubation had no effect on tumour cell adhesion. These results prove that IL‐1β and EGF are significant promoting factors in tumour cell adhesion to mesothelium in vitro and may therefore account for tumour recurrence in the peritoneum in vivo. Copyright

Phaeochromocytomas and sympathetic paragangliomas

About 24 per cent of phaeochromocytomas (PCCs) and sympathetic paragangliomas (sPGLs) appear in familial cancer syndromes, including multiple endocrine neoplasia type 2, von Hippel–Lindau disease, neurofibromatosis type 1 and PCC–paraganglioma syndrome. Identification of these syndromes is of prime importance for patients and their relatives. Surgical resection is the treatment of choice for both PCC and sPGL, but controversy exists about the management of patients with bilateral or multiple tumours.

A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals.

Objective Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. Design Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. Results Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. Conclusions EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.