Guideline Compliance in Surgery for Thyroid Nodules - A Retrospective Study.

Diagnostic guidelines for thyroid nodules focus on malignancy risk assessment to avoid unnecessary diagnostic operations. These guidelines recommend a combination of tests in form of a diagnostic algorithm. The present study analyzed the recommended algorithm and its implementation by different medical professionals. Preoperative diagnostic procedures, laboratory tests and histopathological findings of patients who underwent thyroid surgery between 2006 and 2013 were analyzed. The results were stratified by the assignation by specialized endocrinologists (ENP), general practitioners (GP) or Goethe-University Hospital Frankfurt (UKF). 677 patients were enrolled, of these 62% were assigned by UKF, 18.5% by an ENP and 19.5% by a GP. Ultrasonography rate was significantly higher in UKF (97.6%) compared to patients assigned by GP (90.9%, p<0.0001). Rates for fine-needle aspiration cytology ranged between 47.6% in UKF and 23.2% in ENP (p<0.0001). In over 93% of the patients an analysis of thyroid-stimulating hormone and triiodothyronine/thyroxin was realized. The overall malignancy rate was 11.82%. The malignancy rate was significantly higher if a FNA biopsy was performed (16.35 vs. 8.94%; p=0.0048). A higher malignancy rate could only be seen if the preoperative diagnostic workup included FNA. Besides this, the grade of algorithm adherence showed no effect on the malignancy rate.

Is it safe to perform rectal anastomosis in gynaecological debulking surgery without a diverting stoma?

AIM: Colorectal resection is frequently performed during cytoreductive surgery for gynaecological malignancy. The aim of this study was to assess the safety of colorectal anastomosis, and especially low rectal anastomosis, in the absence of a protective stoma in patients with gynaecological cancer and peritoneal metastasis. METHOD: Patient data were retrospectively collected from a database for gynaecological cancer procedures carried out between January 2013 and July 2015. All patients who underwent a colorectal resection during cytoreduction were included in the study. The primary outcome was anastomotic leakage in the presence or absence of a diverting stoma. Secondary outcome parameters were complications and reoperations. RESULTS: In the period of study, 43 major colorectal procedures were performed on 37 women. The most common colorectal procedure was low rectal resection (n = 22; 59%) followed by anterior rectal resection (n = 7; 19%) and sigmoid resection (n = 4; 11%). Five (14%) patients underwent Hartmann's procedure. In three (8%) patients, a diverting loop ileostomy was created. CONCLUSION: Low rectal resection during debulking procedures for gynaecological cancers with peritoneal carcinomatosis can safely be performed by an experienced surgeon without a diverting stoma.

Proctologic surgery done by residents - Complications preprogrammed?

INTRODUCTION: In current literature, the participation of residents in surgical procedures is discussed as a negative outcome factor, particularly due to an increase of postoperative complications. This study investigated whether minor proctologic surgery with resident participation has a higher rate of postoperative complications. PATIENTS AND METHODS: All patients who underwent an elective Milligan-Morgan hemorrhoidectomy or a resection of pilonidal sinus with rotational flap closure between January 2007 and December 2013 where included in a retrospective database. Primary outcome measure was postoperative complications rate with and without resident participation. RESULTS: Forty-two (6 females: 36 males) patients underwent resection of pilonidal sinus and 61 (17 females: 44 males) patients received a hemorrhoidectomy. Twenty-two patients with pilonidal sinus and 26 patients with hemorrhoids were operated by residents. There were no differences in patient demographics. Residents need significantly more time to perform a pilonidal sinus resection (54min vs. 34.5min; P = 0.004). For hemorrhoidectomy, there were no significant differences in operative time (24min vs. 23.5min; P = 0.656). There were no significant differences in the resident and the consultant group, neither in hemorrhoidectomy nor in pilonidal sinus resection regarding readmission or outpatient visits. In the group of patients with pilonidal sinus resections, 3 patients developed a recurrence, leading to a recurrence rate of 7.1% without significant differences between the two groups (0 vs. 3; P = 0.09). CONCLUSION: The participation of residents in proctologic procedures is not associated with higher postoperative complication rates. Residents should be exposed to proctology procedures on a regular basis, even though the operative time will be prolonged.

Case report-delayed splenic rupture in combination with medial femoral neck fracture after low energy trauma. Development of hemorrhagic shock 5 days after hip prosthesis due to a rare cause.

A 79 year old female patient was admitted to our emergency department with a fracture of the right medial femoral neck six days after a fall on her right side and a cemented hemiprosthesis was implanted. Five days later, she developed a hemorrhagic shock and was diagnosed with a delayed splenic rupture and the spleen was resected. Histopathological examination showed a delayed rupture of an otherwise normal spleen without signs of an underlying pathology. The outcome was fatal: In the postoperative course she developed pneumonia, three weeks later she succumbed due to multiple organ failure. Even careful reevaluation of the case did not provide any clues to expect an injury of the spleen according to trauma mechanism. This case shows that delayed splenic rupture of a normal spleen may occur even after a low energy trauma. Injury of the spleen should therefore always be considered, even with an uncharacteristic anamnesis. Physical examination after trauma should therefore always include a careful clinical evaluation. The clinical threshold for a FAST examination should be low. The coincidence of a femoral neck fracture and a splenic rupture after a low energy trauma has not been reported before.

PATIENTS' SAFETY AND FEASIBILITY OF INTRAVENOUS URAPIDIL IN THE PRETREATMENT OF PHEOCHROMOCYTOMA PATIENTS IN A NORMAL WARD SETTING - AN ANALYSIS OF 20 CONSECUTIVE CASES.

CONTEXT: The intravenously administered selective α1 antagonist urapidil represents an alternative to phenoxybenzamine in the preoperative treatment of pheochromocytoma patients. OBJECTIVE: The aim of the study was to investigate the blood pressure changes in pheochromocytoma patients with urapidil pretreatment with special regards to the need for interventions in order to estimate the safety of this treatment in a normal ward setting. DESIGN: The medical records of all patients who underwent adrenalectomy for PCC were reviewed retrospectively. Systolic blood pressure values >180mmHg were defined as hypertensive episodes and systolic blood pressure values < 50mmHg as hypotensive episodes. Episodes of blood pressure instabilities were considered significant and recorded as intervention if they led to a direct action. RESULTS: Twenty consecutive patients who received urapidil pretreatment were enrolled in this retrospective study. Preoperatively, a median of 9 blood pressure measurements per day have been performed on the ward. A total of 2 episodes of hypertension occurred, and 1 episode of hypotension has been recorded. In the period from 25-72 hours postoperatively the median number of blood pressure measurements was 5 per 24 hours. The blood pressure deviations led to a total of 3 interventions for hypertension in 1 (5%) patients and 5 interventions for hypotension in 3 (15%) patients. All interventions could be managed on the normal ward, without the need to transfer the patient to an ICU. CONCLUSIONS: Intravenous urapidil can safely be administered on a normal ward without putting patients at risk. Intensive monitoring beyond 24 hours postoperatively was not necessary, the blood pressure measurements during the shift on a normal ward were sufficient for maintaining patients' safety.

PALB2 mutations in European familial pancreatic cancer families.

Recently, PALB2 was reported to be a new pancreatic cancer susceptibility gene as determined by exomic sequencing, as truncating PALB2 mutations were identified in 3 of 96 American patients with familial pancreatic cancer (FPC). Representing the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) and the German National Case Collection for Familial Pancreatic Cancer (FaPaCa), we evaluated whether truncating mutations could also be detected in European FPC families. We have directly sequenced the 13 exons of the PALB2 gene in affected index patients of 81 FPC families. An index patient was defined as the first medically identified patient, stimulating investigation of other members of the family to discover a possible genetic factor. None of these patients carried a BRCA2 mutation. We identified three (3.7%) truncating PALB2 mutations, each producing different stop codons: R414X, 508-9delAG and 3116delA. Interestingly, each of these three families also had a history of breast cancer. Therefore, PALB2 mutations might be causative for FPC in a small subset of European families, especially in those with an additional occurrence of breast cancer.

Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families.

Families with both melanoma and pancreatic cancer are extremely rare and some are affected with the autosomal dominant inherited familial atypical multiple mole melanoma-pancreatic cancer (FAMMM-PC) syndrome. The phenotypic and genotypic expressions of such pancreatic cancer-melanoma prone families are not well defined. The National Case Collection of Familial Pancreatic Cancer of the Deutsche Krebshilfe includes 110 pancreatic cancer families, 18 of which (16%) show an association of pancreatic cancer and melanoma. These 18 families were analysed regarding their phenotype and the prevalence of germline mutations in the candidate genes CDKN2A, BRCA2, CHEK2, NOD2, ARL11 and Palladin (PALLD). There were two types of families: five families with the FAMMM-PC phenotype and 13 PC/melanoma families without the multiple mole phenotypes (PCMS). The prevalences of PC and melanoma in the two types of families were similar. The prevalence of other tumour types, especially breast carcinoma, was higher (11%) in PCMS- than in FAMMM-PC families (2.4%, p = 0.02). CDKN2A mutations were identified in 2 of 18 (11%) PCMS families. A cosegregating BRCA2 mutation was detected in one PCMS family without breast cancer. None of the reported germline mutations in the NOD2, Palladin, ARL11 or CHEK2 genes were detected in either type of family. In conclusion, families with an accumulation of PC and melanoma show a large variety of phenotypic expression, which is not always consistent with the FAMMM-PC phenotype. More PC/melanoma-prone families need to be analysed to clarify whether such families represent variations of the FAMMM-PC syndrome or two distinct hereditary cancer syndromes.

Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer.

OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme. AIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years. METHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography. RESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1). CONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.

Color-coded duplex endoscopic ultrasound of the adrenals.

Imaging of the adrenals by endoscopic ultrasound (EUS) is a valuable technique for detection and localization of adrenal lesions, but endosonomorphological tumor distinction remains difficult. In this single-center study, the amount of blood flow in common adrenal lesions, such as adrenal adenomas, adrenal hyperplasia, and pheochromocytomas, was visualized by color-coded duplex EUS (CD-EUS) and was retrospectively analysed. Therefore, we reviewed our EUS database to evaluate and correlate the perfusion patterns of common adrenal lesions with histologically confirmed diagnosis, possible malignancy, and endosonomorphological features such as echogeneity, echostructure, and tumor size. CD-EUS was performed using an endosonoscope Pentax FG 32 UA with a longitudinal 7.5 MHz sector array and Hitachi EUB 525 ultrasound system. In 38 consecutive patients (male=19; female=19; age: mean 53+/-16 yr SD), perfusion patterns of 46 histologically confirmed adrenal, para- or extra-adrenal lesions of adrenal origin (adenoma: no.=20; nodular hyperplasia: no.=11; pheochromocytoma: no.=15; diameter 26+/-15 mm, range 6-70 mm) were analyzed and classified semiquantitatively as "not" (no.=24), "slightly" (no.=12), "moderately" (no.=4) or "highly" (no.=6) hypervascularized. Compared to adenomas (p=0.003) and nodular hyperplasia (p=0.047), pheochromocytomas showed a significantly higher grade of perfusion. There was no relationship between perfusion patterns and localization of pheochromocytomas (adrenal: 8; paraadrenal: 3; extra-adrenal: 4). Vascularization was not statistically associated with tumor echogeneity, echostructure, malignancy or tumor size. CD-EUS is an additional tool for adrenal endosonographic tumor distinction and seems to improve the endosonographic detection of pheochromocytomas by visualization of hypervascularization. As an overlap of perfusion patterns exists, CD-EUS findings must be interpreted in the context of clinical, laboratory and chemical results.

[Hereditary pancreatic cancer]. / Hereditäres Pankreaskarzinom.

An inherited predisposition to pancreatic cancer (PC) is prevalent in about 3% of PC cases and is currently believed to occur in three distinct clinical settings, (1) hereditary tumour predisposition syndromes with an increased risk of PC such as Peutz-Jeghers syndrome and familial atypical multiple mole melanoma, (2) hereditary pancreatitis and cystic fibrosis, in which genetically determined early-age changes of the pancreas can predispose to the development of PC, and (3) familial pancreatic cancer syndrome (FPC). According to a recent consensus conference, high-risk individuals from PC-prone families should be enrolled in board-approved, prospective, controlled screening programs at expert centres. Based on the available data, prophylactic pancreatectomy is not indicated, since the underlying causative gene defect of the FPC syndrome is still unknown and the penetrance of PC in other tumour predisposition syndromes is either low or yet undetermined. In case of the diagnosis of a PC or high-grade precursor lesions, a prophylactic extension of the resection can be considered, since patients with hereditary PC often develop multifocal pancreatic lesions.

Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer.

BACKGROUND AND AIMS: Pancreatic cancer is among the most dismal of human malignancies. Current therapeutic strategies are virtually ineffective in controlling advanced, metastatic disease. Recent evidence suggests that the Hedgehog signalling pathway is aberrantly reactivated in the majority of pancreatic cancers, and that Hedgehog blockade has the potential to prevent disease progression and metastatic spread. METHODS: Here it is shown that the Hedgehog pathway is activated in the Pdx1-Cre;LsL-Kras(G12D);Ink4a/Arf(lox/lox) transgenic mouse model of pancreatic cancer. The effect of Hedgehog pathway inhibition on survival was determined by continuous application of the small molecule cyclopamine, a smoothened antagonist. Microarray analysis was performed on non-malignant human pancreatic ductal cells overexpressing Gli1 in order to screen for downstream Hedgehog target genes likely to be involved in pancreatic cancer progression. RESULTS: Hedgehog inhibition with cyclopamine significantly prolonged median survival in the transgenic mouse model used here (67 vs 61 days; p = 0.026). In vitro data indicated that Hedgehog activation might at least in part be ascribed to oncogenic Kras signalling. Microarray analysis identified 26 potential Hedgehog target genes that had previously been found to be overexpressed in pancreatic cancer. Five of them, BIRC3, COL11A1, NNMT, PLAU and TGM2, had been described as upregulated in more than one global gene expression analysis before. CONCLUSION: This study provides another line of evidence that Hedgehog signalling is a valid target for the development of novel therapeutics for pancreatic cancer that might be worth evaluating soon in a clinical setting.

[Operative management and long-term survival in patients with neuroendocrine tumors of the pancreas--experience with 144 patients]. / Operative Therapie und Langzeitüberleben bei neuroendokrinen Pankreastumoren--Erfahrungen bei 144 Patienten.

BACKGROUND AND OBJECTIVE: To evaluate the outcome of patients with pancreatic endocrine tumors (PETs) in a tertiary referral centre. METHODS: 144 patients with PETs that underwent surgery between 1987 and 2005 at our institution were retrospectively evaluated. The diagnosis of gastrinoma, insulinoma, vipoma and non-functioning PETs was based on clinical symptoms, biochemical tests and histopathology. RESULTS: 144 patients were identified for this study, 20% with a MEN1-syndrome. 172 operations were performed, 122 initial operations and 50 reoperations. Enucleation of the tumor and distal pancreatic resections were the main type of operations. In 23 patients liver metastases were resected. After a median follow up of 67 months (range 1-339), 74 of 144 (51%) patients are still alive without evidence of disease. No patient with a benign tumor and no MEN1-patients died because of PETs. The 5, 10, and actuarial 20-year survival rate for patients with malignant tumors were 75%, 70% and 65%, respectively. The survival rate was significantly related to the type of tumor (benign vs. malignant: p = 0.0002), the patients age at time of initial operation (<50 years vs. >50 years: p = 0.0007), the genetic background of the tumor (sporadic vs. MEN1: p = 0.0312) and the development of metastases after the initial operation (none or lymph node metastases vs. distant metastases: p = 0.01). CONCLUSION: We show that an aggressive surgical approach leads to cure in patients with benign PETs. Although long-term cure can only be achieved in a proportion of patients with malignant PETs, significant long-term palliation can be achieved.