Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases: an in-patient randomised controlled trial (LUTIA).

PURPOSE: Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1-2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity. METHODS: Twenty-seven patients with grade 1-2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a "second-pass" effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test. FINDINGS: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle. CONCLUSION: Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial.

BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.

Influence of lanreotide on uptake of 68Ga-DOTATATE in patients with neuroendocrine tumours: a prospective intra-patient evaluation.

INTRODUCTION: Somatostatin receptor imaging with PET is the standard of care for patients with a neuroendocrine tumour (NET). Since therapy and imaging with somatostatin analogues utilize the same receptor, current guidelines recommend withdrawing long-acting somatostatin analogues for 3-4 weeks prior to somatostatin receptor PET imaging. The aim of this study is to prospectively assess the effect of lanreotide use on the uptake of 68Ga-DOTATATE intra-individually 1 day prior to and 1 day post injection of lanreotide. METHODS: Thirty-four patients with metastatic and/or unresectable NET and currently on lanreotide therapy for at least 4 months were included in the study. A 68Ga-DOTATATE PET/CT scan was performed on the day before and the day after lanreotide injection. In each patient 68Ga-DOTATATE uptake (SUVmax, mean, peak) was assessed in both tumour lesions and normal tissue. All scans were assessed by two blinded nuclear medicine physicians for visual analysis. Paired T-tests were performed to determine the differences between the scans. RESULTS: Of the 34 patients included, 31 were available for analyses in which 190 tumour lesions were measured. Uptake of 68Ga-DOTATATE in tumour lesions was increased significantly after lanreotide, but decreased significantly in the liver, spleen, and thyroid gland resulting in a higher tumour-to-liver ratio. CONCLUSION: Lanreotide injection prior to 68Ga-DOTATATE PET/CT does not result in decreased tumour uptake. In contrast, tumour uptake was increased, whereas the uptake in normal organs is decreased, leading to an increased tumour-to-liver ratio. However, these differences were small and not deemed clinically relevant. These results strongly suggest that discontinuation of lanreotide injections in the weeks prior to 68Ga-DOTATATE PET examinations is unnecessary and does not compromise nuclear medicine imaging results.

Long-term olive oil-based parenteral nutrition sustains innate immune function in home patients without active underlying disease.

BACKGROUND & AIMS: It remains unclear whether impaired host defenses contribute to the increased risk for infectious complications seen in patients on home parenteral nutrition (HPN). The aim of this study was to compare the innate immune function of patients on olive oil-based HPN with that of healthy controls. METHODS: Innate immune functions and (anti-)oxidant balance were studied in 20 patients on olive oil-based HPN without an active underlying immune-mediated disease (Clinoleic(®), ≥ 6 months; >3 times/week), and 21 age- and sex-matched healthy controls. RESULTS: Neutrophils of patients and controls had a similar capacity to eliminate Streptococcus pneumoniae. Also, levels of activation markers (CD66b, CD11b, CD62L) in granulocytes and monocytes, phorbol ester- and zymosan-induced neutrophil oxygen radical production were not different between patients and controls. No differences in (anti-)oxidant status were found, except for higher concentrations of oxidized glutathione and lower plasma selenium and vitamin C in patients compared to controls. CONCLUSION: Compromised innate immune function does not seem to explain the increased risk for infectious complications in HPN patients using olive oil-based lipid emulsions.

A case of esophageal duplication cyst with a 13-year follow-up period.

Benign esophageal cysts are very rare embryonic malformations. In adults, esophageal cysts are mostly asymptomatic. Complications can occur due to mass effects. The diagnosis can be made using endoscopic ultrasonography (EUS), which is regarded as the diagnostic test of choice. It is a matter of debate whether relatively asymptomatic esophageal duplication cysts should be removed or whether conservative management is feasible. We report here on the case of a 37-year-old woman who presented with mild upper abdominal complaints and who was found to have compression of the distal lumen on barium esophagography. It was possible to diagnose an esophageal duplication cyst with EUS. In view of the absence of symptoms, it was decided to provide conservative management. During a 13-year follow-up period, no growth of the cyst was documented, nor did symptoms develop during this period. Close EUS observation may eliminate the need for surgery in asymptomatic patients.

Recurrent pancreatitis after trimethoprim-sulfamethoxazole rechallenge.

We report a female patient who repeatedly developed pancreatitis after trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as prophylaxis for pyelonephritis for many years. The patient presented with abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX use, could be identified. A causal relationship was confirmed by relapse of the pancreatitis after rechallenge. Our case is unique in demonstrating that acute pancreatitis related to the use of TMP/SMX may occur even after long-term treatment. We advise that the medication is discontinued immediately if a causal relationship with pancreatitis is suspected.