Reconstruction for Symptomatic Vertebral Artery Lesion Using Vertebral Artery to Carotid Artery Transposition: A Retrospective Study.

BACKGROUND: A posterior circulation infarction is caused by a vertebral artery (VA) lesion (stenosis or occlusion). The purpose of this study is to assess early and long-term outcomes after open surgery for a VA lesion at the origin. METHODS: In a retrospective study conducted from January 1, 2000 through March 31, 2020 in a single center, patients were treated with vertebral artery to carotid artery transposition (VCT). RESULTS: A total of 28 patients, with a mean age of 65.29 ± 9.81 years (range 45-84), were screened, including 22 patients with VA stenosis and 6 patients with VA occlusion. The complication rate was 21.4% (n = 6), including Horner syndrome (n = 2), lymphocele (n = 1), respiratory failure (n = 1), embolism of a subclavian artery stenosis (n = 1), and vocal cord paralysis (n = 1). The 30-day mortality rate was 0%. Primary patency was 100%. Overall, improvement in symptoms was 85.7% (n = 24) after surgery and 96.4% after 30 days. In the long-term results, primary patency was 100%, and the cumulative patency rate after 60 months was 85.7%, with 1 occlusion of the VA. Cumulative survival rates were 94%, 87%, 69%, and 59% after 12, 24, 60, and 72 months (n = 5). One of the 3 patients died after 60 months because of VA occlusion and posterior circulation infarction. CONCLUSIONS: VCT is a safe, effective, and durable procedure. It provides good stroke protection, symptomatic relief, and perioperative risk at acceptable levels, in experienced hands.

Long-term outcome of surgical resection in patients with gastroenteropancreatic neuroendocrine neoplasia: results from a German nation-wide multi-centric registry.

BACKGROUND: Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB). RESULTS: Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC. CONCLUSION: The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.

Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis.

The association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%-40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver ("hepatic mitochondrial flexibility") at early stages of obesity-related insulin resistance, which is subsequently lost in NASH.

New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) according to their proliferation index into G1- or G2-neuroendocrine tumors (NET) and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC). Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1) or lymph node metastases (NEC-DUE2) from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

"Cherry picking", a multiple non-anatomic liver resection technique, as a promising option for diffuse liver metastases in patients with neuroendocrine tumours.

INTRODUCTION: Liver metastases of GEP-NETs are a known major prognostic factor with a strong effect on patients' survival. To date, various treatment options are available, whereas surgery remains the only curative option. Because large liver resections often cannot be performed due to insufficient remnant liver volume, a special operative technique, "cherry picking" (multiple nonanatomic liver resections), can be used as a tissue-preserving procedure. METHODS: Of 91 patients with various GEP-NETs, 16 patients were identified with synchronous or metachronous multifocal, bilobular liver metastases (>10). All were treated with "cherry picking." Patient records were reviewed retrospectively and clinical data and pathology results were analyzed. RESULTS: Mean survival after primary tumour resection was 82.8 versus 41.2 months after liver surgery. All 16 patients are still alive. Mean recurrence-free survival after primary tumour operation was 49.8 versus 24.6 months after liver surgery. Complications of cherry picking included two postoperative biliary leakages and three small hepatic abscesses (conservative/interventional approach 25 % (n = 4), surgical approach 6.25 % (n = 1). There was no postoperative mortality. Initial hormonal symptoms (5/16 patients) completely disappeared postoperatively in 2 patients and were significantly decreased in 3 patients. CONCLUSIONS: The tissue-preserving surgical technique "cherry picking" has developed due to improved imaging techniques and increased knowledge in liver anatomy, which has helped to make this approach safer and easier. Highly selected patients with multiple bilobular liver metastases of GEP-NET can benefit from this special surgical approach, also applicable for recurrent metastases.

Notch 1 tumor expression is lacking in highly proliferative pancreatic neuroendocrine tumors.

To date, very little is known about the development of benign organic hyperinsulinism and its metastatic potential. Typical morphologic, biochemical, or genetic differentiations for benign or malign tumor course of insulinomas do not exist. As signaling pathways may affect pancreatic cancer development and the maintenance of the neoplastic phenotype, the purpose of this study was to examine the role of Notch1 expression in organic hyperinsulinism. We examined 32 well-differentiated pancreatic endocrine tumors (wd PET); 11 wd PET of unknown behavior (wd PET ub); and 15 wd pancreatic endocrine cancer (wd PEC) for Notch1 expression by immunohistochemistry. Demographic data, clinical data, and follow-up of all patients were analyzed. Islets of the Langerhans show the strongest Notch1 staining in nearly 90 %. Positive Notch1 staining was absent in the acinar of the pancreas. In patients with a wd PET more than every second tumor (56.3 %/n = 18/32) demonstrated a negative Notch1 staining. The other 14 patients were positive for Notch1. Tumors of unknown behavior (wd PET ub) and malignant insulinomas had no signs of Notch expression in contrast to benign insulinomas. Considering the clinical and histomorphological tumor behavior, no correlation between Notch1 expression and clinical data was found. The missing Notch expression in the malignant tumor course might be used as a potential predictive marker, but further studies are needed to investigate the underlying molecular mechanism.

Non-colorectal, non-neuroendocrine, and non-sarcoma metastases of the liver: resection as a promising tool in the palliative management.

PURPOSE: Hepatic resection is established as a safe procedure for colorectal, neuroendocrine, and sarcoma liver metastases. The present study evaluates whether liver resection is an option for patients with non-colorectal, non-neuroendocrine, and non-sarcoma metastases of the liver. METHODS: According to data from our prospective clinical tumor registry, we reviewed the medical records of 44 consecutive patients with non-colorectal, non-neuroendocrine, and non-sarcoma liver metastases, who underwent hepatic resection from January 2000 to December 2008. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. RESULTS: Following hepatic resection, mean overall survival was 21 months, and 5-year survival was 20%. Following hepatic resection, gender, histology, and chemotherapy were of prognostic value in our patient cohort in univariate analysis (p < 0.05). Multivariate survival analysis confirmed chemotherapy (p = 0.002) as an independent prognostic variable. Following initial resection of the primary tumor, synchrone occurrence of metastases, histology, localization of primary, perioperative complications, interval between initial resection of the primary tumor and resection of the metastases, and metastases in follow-up after hepatic resection were of prognostic value in univariate analysis (p < 0.05). Histology (p = 0.017) and interval between resection of the primary and resection of the metastases (p = 0.030) were confirmed as independent prognostic variables in multivariate survival analysis. CONCLUSIONS: Hepatic resection seems to be a safe and promising additive for a selective group of patients with non-colorectal, non-neuroendocrine, and non-sarcoma metastases of the liver.

Multiple giant scalp metastases of a follicular thyroid carcinoma.

BACKGROUND: The occurrence of skin metastases are rare events in the course of a follicular thyroid carcinoma (FTC) and usually indicate advanced tumor stages. The scalp is the most affected area of these metastases. CASE PRESENTATION: We present a case of a 76 year old Woman with multiple giant scalp metastases of a follicular carcinoma. These metastases had been resected and wounds had been closed with mesh graft. The 14-months follow up is presented. CONCLUSION: We demonstrate another case with multicentric form. Because of its location and size a primary wound closure was not possible. A healing could be reached using vacuum therapy and mesh graft transplantation.

Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features.

Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal reflux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zurich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished from tumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1-associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1-associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1-associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas.

Primary hyperparathyroidism in the young age group: particularities of diagnostic and therapeutic schemes.

Primary hyperparathyroidism (pHPT) is a rare endocrine disease in children and young adults. The widespread use of new developments in pHPT surgery (i.e., unilateral and minimally invasive approaches) is based on the assumption that the solitary adenoma is the predominant intraoperative finding, but it has not been evaluated in the subgroup of young patients. From April 1986 to December 2002, a total of 1219 patients with pHPT have been operated on in our institution. The records of 64 patients (5.3%) younger than 30 years were extracted and compared to those of the older patients. The study group (median age 25 years, range 11-30 years) had significantly less bone pain, fewer signs of bone demineralization, and fewer neuropsychiatric symptoms. Eleven patients had hereditary disease. We found a solitary adenoma in only 32 of the 64 juvenile patients (p < 0.001), multiple gland disease in 25 patients (p < 0.001), and two suspected carcinomas. No adenoma could be identified in five patients. Follow-up of 54 patients after a median of 6.1 years revealed 42 normocalcemic patients, 5 hypocalcemic patients, and 7 patients with hypercalcemia. Altogether, 16 juvenile patients underwent parathyroid reoperations (25%) compared to 105 older patients (9%) (p = 0.003). Problems and difficulties with parathyroid surgery are pronounced in younger patients. The high rate of multiple gland disease requires bilateral cervical exploration as the standard procedure in pHPT patients younger than 30 years of age.

Incidentally found medullary thyroid cancer: treatment rationale for small tumors.

The object of this study was to assess the extent of surgery required for small sporadic medullary thyroid cancers (sMTCs). We retrospectively studied 261 patients with MTCs treated in our institution between 1986 and 2002 and identified 15 patients with small pT1 or pT2 sMTCs. The tumors were diagnosed incidentally, so surgical therapy was less than total thyroidectomy. Total thyroidectomy with or without neck dissection was applied to all other patients as standard surgical treatment of care. Patients were systematically followed up by postoperative ultrasonography, calcitonin, carcinoembryonic antigen levels, and pentagastrin stimulation tests. On long-term follow-up over a period of 4.6 years, the rate of biochemical cure in these patients who underwent less than total thyroidectomy for a sporadic incidentally diagnosed tumor was 100%. We concluded that completion thyroidectomy and neck dissection are not mandatory in patients in whom a solitary small sMTC is incidentally discovered by histologic diagnosis following operation so long as a genetic background is excluded. Nevertheless, such patients require systematic careful long-term follow-up.