Metachronous hepatic resection for liver only pancreatic metastases.

BACKGROUND: The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. METHODS: We performed a retrospective, multicenter study including patients undergoing hepatectomy for metachronous PDAC liver metastases between 2004 and 2015 to analyze postoperative outcome and overall survival. All patients were operated with curative intent. Patients with oligometastatic metachronous liver metastasis with definitive chemotherapy (n = 8) served as controls. RESULTS: Overall 25 patients in seven centers were included in this study. The median age at the time of LR was 63.8 years (56.9-69.9) and the median number of metastases in the liver was 1 (IQR 1-2). There were eight non-anatomical resections (32%), 15 anatomical minor (60%) and 2 major LR (8%). Postoperative complications occurred in eleven patients (eight Clavien-Dindo grade I complications (32%) and three grade IIIa complications (12%), respectively). The 30-day mortality was 0%. The median length of stay was 8.6 days (IQR 5-11). Median overall survival following LR was 36.8 months compared to 9.2 months in patients with metachronous liver metastasis with chemotherapy (p = 0007). DISCUSSION: Liver resection for metachronous PDAC metastasis is safe and feasible in selected patients. To address general applicability and to find factors for patient selection, larger trials are urgently warranted.

No alteration of Cyp3A4 activity after major hepatectomy in the early postoperative period - A prospective before-after study.

BACKGROUND: The impact of major liver resection (LR) on the detoxifying function of the remaining liver tissue as represented by CYP3A activity has yet to be assessed. Therefore, this study evaluates the changes in CYP3A activity between preoperative values and after liver resection. MATERIAL AND METHODS: To determine CYP3A activity, midazolam (MDZ) was used as a marker substance, 3 µg were applied intravenously one day before surgery and on the 3rd day after surgery. Subsequently blood was withdrawn at 0, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3, 4 and 6 h post application of the study drug. Plasma MDZ and 1-OH-MDZ concentration was assessed using a LC-MS/MS method. Volumetric analysis of the resected liver was done by syngo.CT liver analysis software (Siemens Healthineers) using preoperative multidetector computed tomography. RESULTS: N = 13 (8 male/5 female) patients were included in this study and received preoperative evaluation, 11 patients were studied also after liver resection. The mean age was 62 (±15.3) years with a mean BMI of 23.6 ± 4.8 kg/m2. No patient suffered from acute liver dysfunction postoperatively. None of the pharmacokinetic parameters assessed were significantly altered by liver resection. CYP3A activity over time was not significantly reduced by major liver resection. CONCLUSION: This study gives first time data on the impact of major liver resection on CYP3A activity. It was shown that MDZ clearance representing in vivo CYP3A activity is not altered by major liver resection. This suggests no dose adjustment of commonly applied drugs which are CYP3A substrates needs to be carried out.

Physical recovery after laparoscopic vs. open liver resection - A prospective cohort study.

BACKGROUND: While the number of laparoscopic liver resections (LLRs) is increasing worldwide, its impact on physical recovery remains unclear. We hypothesized that LLR is associated with better physical recovery than open liver resection (OLR). To address this question, we investigated the impact of laparoscopic liver resection compared to open liver resection on physical recovery in a prospective trial. METHODS: Twenty-one patients who underwent LR were included in this study (11 OLR (52.4%) and 10 LLR (47.6%), respectively). Physical recovery was measured by bicycle stress testing at months 1 and 6 after surgery and compared to preoperative stress testing. Standardized performance for bicycle stress testing was calculated based on age, sex, height and weight. Physical recovery was compared between groups as change of performance (%). RESULTS: Median age was 58 years (Inter Quartile Range (IQR): 44-68), and the main indications for LR were colorectal liver metastases (n = 10; 45%) and hepatocellular carcinoma (n = 6; 27%). The one-month change of performance level was -8% (IQR: -12-1) compared to the preoperative level with no significant difference between open and laparoscopic LR (LLR: -8% (-11 - 1); OLR: -6% (-12 - 4), p = 0.833). Furthermore, 6 months postoperatively, patients in both groups had not reached back their preoperative performance level (LLR: -5.7% (-8.4 - 18.6); OLR -4. 8% (-12.6 - 1.9), p = 0.833). CONCLUSION: In this study, we report an impaired physical recovery after LR that was not fully restored 6 months after surgery. There was no significant difference between open and laparoscopic LR in terms of bicycle stress testing. Limitations of the study include the limited sample size and differences, albeit non-statistically significant, in the baseline characteristics of the two groups. To rule out a possible role of age or underlying indication for liver resection on physical recovery, future randomized controlled trials need to be performed.

Gadoxetic acid-enhanced 3.0 T MR imaging versus multidetector-row CT in the detection of colorectal metastases in fatty liver using intraoperative ultrasound and histopathology as a standard of reference.

OBJECTIVE: To compare the diagnostic value of gadoxetic acid-enhanced MRI at 3.0 T with 64-row MDCT in the detection of colorectal liver metastases in diffuse fatty infiltration of the liver after neoadjuvant chemotherapy. METHODS: Twenty-three patients with colorectal liver metastases and at moderate to severe steatosis (25-90%) underwent prospectively preoperative tri-phasic MDCT (Somatom Sensation 64, Siemens) and gadoxetic acid-enhanced MRI (3-T Magnetom Trio, Siemens). All patients underwent surgical resection of liver metastases. Intraoperative ultrasound (IOUS) was carried out, which served as the standard of reference, together with histopathology. RESULTS: Overall, 68 metastases (range, 0.4-6 cm; 31/68 metastases [46%] ≤ 1 cm) were found at histology. MDCT detected 49/68 lesions (72%), and MRI 66/68 (97%, p < 0.001). For lesions ≤ 1 cm, MDCT detected only 13/31 (41.9%) and MRI 29/31 (93%, p < 0.001). Eight false-positive lesions were detected by MDCT, seven small lesions by MRI. There was no statistically significant difference between the two modalities in the detection of lesions > 1 cm (p = 0.250). IOUS detected all metastases and revealed two false-positive diagnoses. CONCLUSION: Gadoxetic acid-enhanced 3.0 T MRI is superior to 64-row MDCT in detecting colorectal liver metastases ≤ 1 cm during preoperative staging in patients with liver steatosis. A combination of MRI and IOUS may further improve the outcome of surgical treatment.

Value of hepatic venous pressure gradient measurement before liver resection for hepatocellular carcinoma.

BACKGROUND: Portal hypertension associated with liver cirrhosis increases the risk of postoperative complications after liver resection for hepatocellular carcinoma (HCC). This study assessed the role of preoperative hepatic venous pressure gradient (HVPG) assessment in identifying portal hypertension. METHODS: All patients who underwent liver resection for HCC between January 2000 and December 2009 at the Department of General Surgery, Medical University Vienna, were analysed retrospectively. HVPG was assessed prospectively in a subset of patients before liver resection. The influence of this assessment on postoperative complications was investigated. RESULTS: A total of 132 patients were enrolled, of whom 39 underwent HVPG measurement. Mean(s.d.) HVPG was 6·4(3·0) and 4·3(1·4) mmHg in patients with and without postoperative complications respectively (P = 0·028). Complication rates differed significantly at a cut-off HVPG value of 5 mmHg: 11 of 21 patients with a gradient of 1-5 mmHg developed complications versus 12 of 14 patients with a higher value (P = 0·045). HVPG exceeding 5 mmHg was associated with worse liver fibrosis (P = 0·004), higher rates of postoperative liver dysfunction (5 of 13 versus 1 of 18; P = 0·022) and ascites (7 of 14 versus 3 of 21; P = 0·022), and a longer hospital stay (median (range) 11 (7-26) versus 8 (4-20) days; P = 0·034). Overall postoperative morbidity did not differ between patients who had preoperative HVPG assessment and those who did not (P = 0·142). CONCLUSION: Preoperative HVPG assessment predicted liver fibrosis and postoperative complications.

Lymph node ratio after curative surgery for intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is rare but its incidence is rising worldwide. The value of lymph node dissection for ICC is under discussion; the current staging systems do not differentiate between numbers of involved nodes. METHODS: Ninety-three patients who underwent laparotomy for ICC between 1997 and 2007 were identified retrospectively; 46 who underwent curative resection and systematic lymphadenectomy around the hepatoduodenal ligament were analysed further. Univariable and multivariable regression analysis was performed to identify prognostic factors. RESULTS: Tumour size and advanced tumour stage were associated with worse overall and recurrence-free survival in univariable analysis. An increased ratio of positive to total harvested lymph nodes (LNR) was also prognostic for adverse outcome in lymph node-positive patients: crude hazard ratio 8.93 (95 per cent confidence interval (c.i.) 1.52 to 32.50) for overall survival and 8.76 (1.96 to 39.22) for recurrence-free survival. Adjusted hazard ratios for LNR in multivariable regression analysis were 9.81 (1.52 to 43.44) and 10.63 (2.04 to 55.31) respectively. The total number of retrieved lymph nodes was not related to survival or recurrence. CONCLUSION: LNR appears to be a good prognostic factor for survival or recurrence after curative resection for ICC.

Impact of parathyroidectomy on neutrophil cytosolic calcium in chronic kidney disease patients: a prospective parallel group trial.

OBJECTIVES: Polymorphonuclear leucocytes (PMNs) of chronic kidney disease (CKD) patients display elevated basal cytosolic calcium concentrations (iCa(2+)). As parathyroid hormone is considered to substantially contribute to the inappropriate cellular entry of calcium in uraemia, we hypothesized that parathyroidectomy lowers PMN iCa(2+). DESIGN AND SETTING: Prospective parallel group trial at a tertiary care centre. SUBJECTS, INTERVENTION AND MAIN OUTCOME MEASURES: Two patient cohorts (cohort 1: 14 CKD patients; cohort 2: 14 renal transplant recipients) underwent parathyroidectomy for uncontrolled secondary hyperparathyroidism. We assessed PMN iCa(2+) (primary objective) spectrofluorimetrically 1 day before and 20 days after intervention (secondary objective: PMN glucose uptake). Data were compared with those of 16 matched maintenance haemodialysis patients (cohort 3), and to 15 healthy subjects (cohort 4), by generalized estimating equations. RESULTS: PMN iCa(2+) of cohort 1 decreased over time and was significantly higher than that of cohort 3 before but not after parathyroidectomy [mean difference before/after parathyroidectomy: 19.1 nmol L(-1) (95% confidence interval: 9.4-22.4), P =0.0003/-3.2 (-20.9-14.5), P = 0.71]. PMN iCa(2+) of cohort 2 decreased over time, but we found no significant difference in comparison with cohort 3 [mean difference before/after parathyroidectomy: 6.5 nmol L(-1) (-9.4-22.4), P = 0.4/-15.8 (-43.6-12.0), P = 0.25]. PMN iCa(2+) of all CKD patients was substantially higher in comparison with that of healthy subjects [cohort 4 vs. 3: -35.3 (-48.9-21.6), P < 0.001]. PMN glucose uptake increased significantly in both interventional cohorts in comparison with cohort 3. CONCLUSIONS: Parathyroidectomy lowers, but does not normalize PMN iCa(2+) of CKD patients. Further variables, possibly uraemic retention solutes, control both PMN iCa(2+) and functional responses.

Importance of tumour size in papillary and follicular thyroid cancer.

BACKGROUND: The most controversial change in the new pathological tumour node metastasis (pTNM) classification of thyroid tumours is the extension of the pT1 classification to include tumours up to 20 mm. METHODS: Four hundred and three patients with pT1 or pT2 differentiated thyroid carcinomas were divided into three groups according to tumour diameter (group 1, 10 mm or less; group 2, 11-20 mm; group 3, 21-40 mm). They were analysed retrospectively with respect to carcinoma-specific and disease-free survival. RESULTS: No patient in group 1 died from papillary thyroid carcinoma, compared with three patients in group 2 and six in group 3. There was a statistically significant difference in carcinoma-specific survival between groups 1 and 2 (P = 0.033). Two patients in group 1, six in group 2 and eight in group 3 developed recurrence. The difference in disease-free survival between groups 1 and 2 was significant (P = 0.025). One patient in group 1, three in group 2 and four in group 3 died from follicular thyroid carcinoma, but there were no significant differences in survival between the three groups. CONCLUSION: Extension of the pT1 classification to cover all tumours up to 20 mm does not appear to be justified for papillary thyroid carcinoma.

Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines.

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine. Eight MTC cell lines were established from seven patients with MTC. IC(50) values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC(50) values were 3.5 +/- 1.2 nmol/liter for CPT and 8.2 +/- 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable. Given peak plasma concentrations of 65 +/- 20 nmol/liter for CPT and 1 micro mol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region.

Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodine-replete endemic goiter region. Six hundred and three patients with DTC treated within a 35-year-period were retrospectively analyzed with respect to carcinoma-specific survival. Prognostic factors were tested for their significance using univariate and multivariate analysis. The histological type (PTC versus FTC) was found to be a highly significant factor - carcinoma-specific survival both in univariate (P<0.001) and multivariate analyses (P=0.003) was significantly different. Univariate analysis revealed patients' age, extra-thyroid tumor spread, lymph node and distant metastases, increasing tumor size, and the tall cell variant to be significant prognostic factors for PTC patients. Age > or =45 years, positive lymph nodes and increasing tumor size were confirmed as independent prognostic factors. Univariate analysis of FTC patients revealed age at presentation, gender, extrathyroidal tumor spread, lymph node and distant metastases, increasing tumor size, multifocality, widely invasive tumor growth and oxyphilic variant to be factors bearing prognostic significance. The presence of distant metastases and increasing tumor size could be identified as independent prognostic factors for FTC patients. This study shows distinctive differences in prognostic factors of PTC and FTC: independent factors predicting poor prognosis are age > or =45 years, positive lymph nodes and increasing tumor size for PTC, and distant metastases and increasing tumor size for FTC. PTC and FTC patients should be analyzed and reported separately.

Combined transmission and (99m)Tc-sestamibi emission tomography for localization of mediastinal parathyroid glands.

AIM: Although parathyroid scintigraphy using (99m) Tc-sestamibi is considered the best preoperative localization method for hyperfunctioning parathyroid tissue it lacks the anatomical details required for successful, minimal invasive surgery of ectopic parathyroid lesions. This study presents the role of combined SPECT/X-ray-CT imaging in a single device for localization of mediastinal parathyroid glands. METHODS: (99m) Tc-sestamibi SPECT/X-ray-CT was performed by gamma camera-mounted anatomical X-ray tomography (GMAXT; GE Medical systems, Millenium VG with Hawkeye) in four patients with ectopic parathyroid glands (two patients with primary, two with persistent secondary hyperparathyroidism). The device contains an X-ray tube and a set of detectors that rotate around the patient combined with a gamma camera. For comparison with GMAXT addition-ally high resolution computed tomography images of the neck and mediastinum were performed. RESULTS: Correct preoperative localization was achieved. The parathyroid glands were located in the anterior mediastinum. High resolution computed tomography could not provide further details. Three patients were operated by a minimal invasive open and one patient by a transsternal approach because of concomitant aortic valve replacement. CONCLUSION: (99m)Tc-sestamibi/X-ray-CT fusion imaging in a single device can accurately localise ectopic or supernumerary mediastinal parathyroid tumours in primary and secondary hyperparathyroidism. Morbidity,radiation exposure, time, and costs are reduced by avoiding multiple diagnostic examinations and minimal invasive parathyroid surgery becomes possible.

Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism.

BACKGROUND: Nesidioblastosis in adults has been reintroduced into the differential diagnosis of organic hyperinsulinism by the description of 'noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)'. MATERIALS AND METHODS: Pathologic specimens of all adult patients (n = 66) operated on for organic hyperinsulinism were re-examined. Five patients fulfilled the histomorphological criteria of nesidioblastosis. Retrospective review of clinical presentation, results of 72-h fasts, intravenous tolbutamide tolerance tests, pre- and intraoperative localization studies and surgical therapy was performed. RESULTS: In contrast to NIPHS, fasting tests became positive after 8-14 h. Tolbutamide tests were positive and preoperative imaging showed negative results in all patients. At first operation distal pancreatic resections were performed in three patients, resection of the pancreatic body in one patient and biopsy of the pancreatic tail in one patient. Two of three patients with recurrent disease had to be reoperated. One patient showed a coexistence of nesidioblastosis and multiple small insulinomas and is part of a kindred with autosomal dominantly inherited 'familial islet-cell adenomatosis'. CONCLUSIONS: Surgical exploration is indicated only after thorough biochemical diagnosis. An aggressive strategy for preoperative localization including selective arterial calcium stimulation testing seems justified. There may be a combination of nesidioblastosis and islet cell tumours. A link between beta-cell hyperplasia and progression to insulinoma based on not yet known genetic causes can be suspected.

Is the new classification of neuroendocrine pancreatic tumors of clinical help?

A new concept of classifying neuroendocrine pancreatic tumors based on clinicopathologic patterns was summarized recently. To evaluate the clinical reliability and prognostic specificity of this classification system, 100 neuroendocrine pancreatic tumors were retrospectively categorized as "benign," "uncertain," and "malignant" based on tumor risk factors (size, local invasion and angioinvasion, cell atypia, metastases) and were followed for disease recurrence and progression. Altogether, 71 functioning tumors (insulinoma, gastrinoma, glucagonoma, enterochromaffin-like (ECL)oma, somatostatinoma) and 29 nonfunctioning neuroendocrine pancreatic tumors (NETs) were studied. NETs had an increased risk of malignancy (p < 0.05). Tumor size, gross invasion, and metastases correlated significantly with tumor behavior and allowed us to distinguish between "benign" and "malignant" tumors. About 89% of the tumors < or = 20 mm were "benign," whereas 71% > 20 mm were "malignant" (p < 0.05). In patients with "benign" and "uncertain" neuroendocrine pancreatic tumors, neither recurrence nor progression of disease was seen. About 41% of the patients with "malignant" tumors died of the disease. The 5-year estimated cumulative survival of those with "benign" and "uncertain" tumors was 100% and 52 +/- 10% for those with "malignant" tumors (p < 0.05). Histomorphologic details classifying the behavior of an "uncertain" tumor are known only after initial treatment and definitive histopathologic investigation. Thus this information is of limited clinical help for treatment strategies.