Markus Krausch

In situ liver transection with portal vein ligation for rapid growth of the future liver remnant in two‐stage liver resection

Portal vein embolization (PVE) has become a standard procedure to increase the future liver remnant (FLR) and enable curative resection of initially unresectable liver tumours. This study investigated the safety and feasibility of a new two‐stage liver resection technique that uses in situ liver transection (ISLT) and portal vein ligation before completion hepatectomy.

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.

Loss of PTEN Expression in Neuroendocrine Pancreatic Tumors

PTEN (phosphatase and tensin homologue deleted from chromosome 10) is a well established tumor suppressor gene, which was cloned to chromosome 10q23. PTEN plays an important role in controlling cell growth, apoptosis, cell adhesion, and cell migration. In various studies, a genetic change as well as loss of PTEN expression by different carcinomas has been described. To date, the role of PTEN as a differentiation marker for neuroendocrine tumors (NET) and for the loss of PTEN expression is still unknown. It is assumed that loss of PTEN expression is important for tumor progression of NETs. We hypothesize that PTEN might be used as a new prognostic marker. We report 38 patients with a NET of the pancreas. Tumor tissues were surgically resected, fixed in formalin, and embedded in paraffin. PTEN expression was evaluated by immunohistochemistry and was correlated with several clinical and pathological parameters of each individual tumor. After evaluation of our immunohistochemistry data using a modified Remmele Score, a widely accepted method for categorizing staining results for reports and statistical evaluation, staining results of PTEN expression were correlated with the clinical and pathological parameters of each individual tumor. Our data demonstrates a significant difference in survival with existence of lymph node or distant metastases. Negative patients show a significant better survival compared with positive patients. Furthermore, we show a significant difference between PTEN expression and WHO or TNM classification. Taken together, our data shows a positive correlation between WHO classification and the new TNM classification of NETs, and loss of PTEN expression as well as survival. These results strongly implicate that PTEN might be helpful as a new prognostic factor.

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.

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.

Splenic Artery Switch for Revascularization of the Liver: A Salvage Procedure for Inflammatory Arterial Hemorrhage

BackgroundHemorrhage caused by inflammatory vessel erosion represents a life-threatening complication after upper abdominal surgery such as pancreatic head resection. The gold standard therapeutic choice is an endovascular minimally invasive technique such as embolization or stent placement. Hepatic arterial hemorrhage in presence of pancreatitis and peritonitis is a particular challenge is if a standard therapeutic option is not possible.MethodsThe management of five patients with massive bleeding from the common hepatic artery is described. All patients underwent a splenic artery switch. The splenic artery was dissected close to the splenic hilum and transposed end-to-end to the common hepatic artery after resection of the eroded part. Patients’ medical records, radiology reports, and images were reviewed retrospectively. Technical success was defined as immediate cessation of hemorrhage and preserved liver vascularization. Clinical success was defined as hemodynamic stability and adequate long-term liver function.ResultsTotal pancreatectomy and splenectomy were performed in four of the five cases. Hemodynamic stability and good liver perfusion was achieved in these patients.ConclusionsSplenic artery switch is an effective, safe procedure for revascularization of the liver in case of hepatic arterial hemorrhage following pancreatic surgery, pancreatitis, and/or peritonitis. The technique is a promising option if a standard procedure—e.g., stent implantation, embolization and surgical repair with alloplastic prosthesis or autologous venous interposition graft—is not possible.

Multiple giant scalp metastases of a follicular thyroid carcinoma

BackgroundThe 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 presentationWe 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.ConclusionWe 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.

Neuroendokrine Neoplasien des distalen Jejunums und Ileums

ZusammenfassungNeuroendokrine Neoplasien (NEN) des distalen Jejunums und Ileums leiten sich von den serotoninproduzierenden enterochromaffinen Zellen (EC-Zellen) ab. Aufgrund ihrer niedrigen proliferativen Aktivität und ihres infiltrativen Wachstums werden sie klinisch häufig in einem fortgeschrittenen metastasierten Tumorstadium diagnostiziert. Die Biologie dieser Tumoren unterscheidet sich grundlegend von NEN anderer Lokalisation. Für eine Vereinheitlichung und Verbesserung der Diagnose und Therapie wurden die Leitlinien für die Diagnostik und das klinische Management von jejunoilealen NEN sowie für das Management von Patienten mit hepatisch und fernmetastasierten NEN durch die European Neuroendocrine Tumor Society (ENETS) im Jahre 2012 überarbeitet. Die folgende Übersicht konzentriert sich auf die für die Pathologie besonders relevanten Sachverhalte und deren Einbettung in das klinische Management.AbstractNeuroendocrine neoplasms (NEN) of the distal jejunum and ileum derive from serotonin-producing enterochromaffin (EC) cells. Due to their low proliferation rate and their infiltrative growth, they are often discovered at an advanced disease stage when metastasis has already occurred. The biology of these tumours is different from other NEN of the digestive tract. In order to standardise and improve diagnosis and therapy, the guidelines for the diagnosis and clinical management of jejuno–ileal NEN as well as for the management of patients with liver and other distant metastases from NEN were revised by the European Neuroendocrine Tumour Society (ENETS) in 2012. This review focuses on aspects relevant for surgical pathology.

Neuroendocrine neoplasms of the distal jejunum and ileum

ZusammenfassungNeuroendokrine Neoplasien (NEN) des distalen Jejunums und Ileums leiten sich von den serotoninproduzierenden enterochromaffinen Zellen (EC-Zellen) ab. Aufgrund ihrer niedrigen proliferativen Aktivität und ihres infiltrativen Wachstums werden sie klinisch häufig in einem fortgeschrittenen metastasierten Tumorstadium diagnostiziert. Die Biologie dieser Tumoren unterscheidet sich grundlegend von NEN anderer Lokalisation. Für eine Vereinheitlichung und Verbesserung der Diagnose und Therapie wurden die Leitlinien für die Diagnostik und das klinische Management von jejunoilealen NEN sowie für das Management von Patienten mit hepatisch und fernmetastasierten NEN durch die European Neuroendocrine Tumor Society (ENETS) im Jahre 2012 überarbeitet. Die folgende Übersicht konzentriert sich auf die für die Pathologie besonders relevanten Sachverhalte und deren Einbettung in das klinische Management.AbstractNeuroendocrine neoplasms (NEN) of the distal jejunum and ileum derive from serotonin-producing enterochromaffin (EC) cells. Due to their low proliferation rate and their infiltrative growth, they are often discovered at an advanced disease stage when metastasis has already occurred. The biology of these tumours is different from other NEN of the digestive tract. In order to standardise and improve diagnosis and therapy, the guidelines for the diagnosis and clinical management of jejuno–ileal NEN as well as for the management of patients with liver and other distant metastases from NEN were revised by the European Neuroendocrine Tumour Society (ENETS) in 2012. This review focuses on aspects relevant for surgical pathology.

Coincidence of Primary Hyperparathyroidism and Nonmedullary Thyroid Carcinoma

The incidence of primary hyperparathyroidism (pHPT) combined with nonmedullary thyroid carcinoma (NMTC) has been reported between 2-13%. To date, it remains controversial whether these 2 pathologies occur coincidental or are caused by specific risk factors or genetic changes. The aim of this study was to evaluate the clinical and histological characteristics of NMTC associated with pHPT. We reviewed prospective database records of 1 464 unselected, consecutive patients who were treated for pHPT in our institution between 1986 and 2012 and identified 41 NMTC (2.8%). The collective consisted of 35 papillary (PTC) and 6 follicular (FTC) thyroid carcinomas. Our collective of 41 NMTC including 34 single adenomas and 7 multiglandular diseases consisted of 33 females and 8 males. Patients with FTC demonstrated significant lower preoperative PTH levels compared to PTC. Interestingly, NMTC were predominantly located on the right side. FTC had significant larger tumors as well as demonstrated increased extrathyroidal growth and lymph node metastases. In 71% pHPT and NMTC were diagnosed synchronously. The comorbidity of pHPT and NMTC occurs in about 3%. As pHPT is often operated by a focal minimally invasive approach, we advocate a mandatory preoperative thyroid ultrasound for all patients with pHPT to be able to identify synchronous thyroid disease.