Martin Schindl

The role of intra-abdominal pressure on splanchnic and pulmonary hemodynamic and metabolic changes during carbon dioxide pneumoperitoneum

BACKGROUND AND METHODS To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.

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 ≤ 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.

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)’.

Stage-dependent Therapy of Rectal Carcinoid Tumors

Abstract. Although malignant behavior of rectal carcinoid tumors is rare, the risk of metastases and death does exist. Adaptation of therapy according to the estimated malignancy seems necessary. To develop a stage-dependent therapy, 31 patients with rectal carcinoid tumors measuring 5 to 50 mm in diameter were analyzed retrospectively. Malignancy was estimated according to tumor size, infiltration depth, and histopathology. There were 18 tumors within the mucosa and submucosa (T1), 7 tumors with muscularis propria invasion (T2), and carcinoid tumor penetrating the full rectal wall (T3) or spreading to surrounding tissue (T4) in 6 patients. Altogether 20 patients (65%) were treated with a minimally invasive intervention: endoscopic polypectomy (EP) in 12 and transanal excision (TE) in 8 patients. In 11 patients (35%) aggressive surgical procedures—anterior resection (AR) in 4 and abdominoperineal resection (APR) in 7—were performed. After a mean ± SD follow-up of 86.0 ± 61.3 months, tumor recurrence was not seen in any of the 20 patients with minimally invasive treatment, and all were still alive. No severe complications associated with surgical procedures were detected. In contrast, 5 of the 10 patients with advanced tumor stage died from their disease despite aggressive surgery (AR, APR). In conclusion, depending on tumor stage, treatment of rectal carcinoids includes EP, TE, or extended resection. Minimally invasive techniques are safe treatments for small to medium-size T1/T2 rectal carcinoids. Extended surgery cannot improve the overall survival of those with advanced tumors (T3/T4, N1, M1) but can be beneficial for preventing local complications.

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.

Post-treatment imaging of liver tumours.

Abstract In the past few years, great improvements have been made to achieve local tumour control of primary liver malignancies and liver metastases. For hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) and tumour ablation techniques, including percutaneous ethanol injection (PEI), radiofrequency ablation (RF), and laser-induced interstitial thermotherapy (LITT) have been developed. For colorectal liver metastases, surgery is still the standard technique in localised disease, although percutaneous RF ablation has gained considerable acceptance. In patients with widespread disease, chemotherapy with new drugs offers improved survival. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice to evaluate treatment response. The present review demonstrates imaging findings of complete and incomplete tumour control after intervention as well as the imaging spectrum of complications. Imaging guidelines according to the World Health Organization and Response Evaluation Criteria In Solid Tumors (RECIST) for assessment of chemotherapy response are presented.

Treatment of small intestinal neuroendocrine tumors: is an extended multimodal approach justified?

Neuroendocrine tumors (NETs) of the small bowel are known for their low malignant behavior. Although most cases are diagnosed in an advanced stage, natural life expectancy is significantly higher than with intestinal carcinomas. The question arises if there are any benefits to combining extended (radical or debulking) surgery, interventional treatment, and medical treatment with respect to life expectancy, and quality of life. A series of 58 patients (34 men, 24 women; mean age 61 ± 12 years, range 37–87 years) with NETs of the small bowel were retrospectively reviewed and prospectively followed over 63 ± 53 months. Clinical presentation, tumor characteristics, and postoperative medical treatment were documented. Quality of life was additionally analyzed using a questionnaire. Survival probability and quality of life were compared for tumor stages and type of treatment performed. In 47 of 58 (81%) patients the NET was diagnosed based on the presence of intestinal stenosis or endocrine symptoms. Of 16 patients without liver metastases, 15 (94%) were cured by radical surgery. Multiple liver metastases were evident in 40 of 58 (69%) patients and decreased the 5- and 10-year cumulative survival to 64% ± 10% and 22% ± 10% (M0 vs. M1: p <0.05). The 5- and 10-year survival rates after multimodal treatment (surgery, bio/immunotherapy, transarterial embolization of liver metastases) were 64% ± 11% and 28% ± 12% compared to 61% ± 15% and 0% in patients without (p = NS). In patients with small intestinal NETs, a consistent multimodal treatment helps to improve the overall survival and, in most patients, the quality of life.

Adequate preoperative staging rarely leads to a change of intraoperative strategy in patients undergoing surgery for colorectal cancer liver metastases

BACKGROUND Diagnostic tools used prior to hepatic surgery have significantly advanced during the last decade. We investigated the value of preoperative staging on detection of additional resectable hepatic lesions in metastatic colorectal cancer patients. METHODS One hundred ninety-four consecutive resections for colorectal liver metastases between January 2002 and December 2005 were prospectively analyzed. Data on imaging (multidetector computed tomography [MDCT] and magnetic resonance imaging [MRI]) were compared to intraoperative findings by intraoperative sonography and bimanual palpation together with histopathological examination. Univariate and multivariate analysis of factors influencing recurrence was performed. RESULTS In 16 (8.2%) resections, additional lesions were detected intraoperatively. In 11 cases (5.7%), these were small (<1 cm) and subcapsular. Detection of additional tumors was associated with shorter median recurrence free survival (5.4 vs. 13.4 months; P < .001) even though all lesions were resected and risk of recurrence was stratified by the Fong score. Patients treated with neoadjuvant chemotherapy did not generally have an increased risk of additional tumors; however, intraoperative detection of new lesions was associated with inferior outcome in this subgroup (median RFS 4.6 vs. 18.3 months in responders, P < .001). CONCLUSION Preoperative imaging with contrast-enhanced MDCT and MRI is efficient and very seldom leads to changes in intraoperative strategy. Patients exhibiting additional resectable hepatic lesions upon surgery have a high risk for early recurrence and should be monitored closely during follow-up.

Can dynamic gadolinium-enhanced magnetic resonance imaging with chemical shift studies predict the status of adrenal masses?

Endoscopic adrenalectomy represents the new gold standard in the surgical treatment of benign adrenal lesions up to 6 cm. In some cases lesions larger than 10 cm have been removed laparoscopically to offer the patient the advantages of the minimally invasive technique. The larger the diameter of an adrenal lesion, the greater the probability of malignancy. In a prospective study 130 consecutive patients (88 women, 42 men; mean age 47.8 years) with 137 adrenal lesions earmarked for surgery underwent preoperative gadolinium-enhanced magnetic resonance imaging (MRI) with chemical shift studies (CSS). The aim of this study was to predict the status (benign, borderline, malignant) of adrenal lesions by MRI irrespective of tumor size. There were 14 patients with malignant tumors, 3 had borderline tumors (epithelial tumors with high malignant potential), and the remaining 120 had benign adrenal lesions. Five malignant lesions (36%) had a diameter < 6 cm. MRI correctly predicted 11 of 14 malignant tumors (1 malignant pheochromocytoma and 2 adrenocortical carcinomas had false-negative results), 117 of 120 benign lesions, and 2 of 3 borderline lesions. All but two malignant tumors were operated on using open surgery; 82 (68%) of 120 benign adrenal lesions were treated using the transperitoneal laparoscopic approach. Tumor size alone is not suitable for predicting the status of adrenal lesions. Dynamic gadolinium-enhanced MRI with CSS can predict the status of at least 95% of adrenal lesions. Tumors > 6 cm classified as benign by preoperative MRI may be removed laparoscopically by endocrine surgeons experienced in endoscopic adrenalectomy.

HER2 gene amplification and protein expression in pancreatic ductal adenocarcinomas.

Background:Despite advances in combination therapies, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Blocking of overexpressed HER2 oncogene improves survival in breast and gastroesophageal cancer and might be also a therapeutic option in PDAC. The purpose of this study was to evaluate HER2 gene amplification and protein expression in PDAC. Methods:HER2 protein expression was investigated using a FDA-approved antibody in 87 formalin-fixed and paraffin-embedded cases of PDAC with complete follow-up. HER2 gene amplification was assessed on tissue microarrays using dual color silver in situ hybridization (DISH). Results:Generally, HER2 immunostaining showed considerable heterogeneity. In 19 cases, ≥10 of tumor cells showed some positive reaction. In no case, complete membranous staining was observed. Using the scoring system developed for assessment of HER2 status in gastroesophageal cancer, 9 cases showed positive immunohistologic staining (score 2+ to 3+). After performing DISH, 6 (7%) immunohistochemically 2+ or 3+ cases were found to have HER2 gene amplification, whereas none of these cases showed polyploidy. No association of HER2 status and clinicopathologic parameters or survival was observed (P>0.05). Conclusions:HER2 is overexpressed in a subset of PDACs, identifying them as possible candidates for a targeted therapy. For assessment of HER2 status in PDAC, the scoring system originally developed for gastric cancer is recommend.