Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study).

BACKGROUND: One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen. METHODS: Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs. RESULTS: This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78·3 per cent of patients avoided SLND (P < 0·001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P < 0·001). Costs were reduced by a mean of 24·5 per cent in women without IBC (€3990 versus 5286; P < 0·001). CONCLUSION: Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).

Meta-analysis of neoadjuvant therapy and its impact in facilitating breast conservation in operable breast cancer.

BACKGROUND: Neoadjuvant therapy (NAT) for operable breast cancer may facilitate more breast-conserving surgery (BCS). It seems, however, that this benefit is not being realized fully. METHODS: A systematic review of the literature was performed. RCTs were included. The criteria for inclusion were: documentation of surgical assessment before and after NAT, surgery performed (BCS or mastectomy), and clinical and pathological responses. RESULTS: A total of 1452 patients from seven RCTs met the inclusion criteria. After NAT, the feasibility of BCS increased from 43·3 to 60·4 per cent (P < 0·001), but BCS was performed in only 51·8 per cent (P = 0·04). Only 31 per cent of patients who became eligible for BCS (assessed on clinical response) underwent BCS (pooled rate ratio 0·31, 95 per cent c.i. 0·22 to 0·44; P < 0·001). Of the mastectomy candidates who achieved a pathological complete response after NAT, only 41 per cent underwent BCS (pooled rate ratio 0·41, 0·23 to 0·74; P = 0·003). The main factors that influenced the decision not to shift to BCS, even though it was feasible, were clinical assessment before NAT, multicentricity and tumour size at presentation. CONCLUSION: Breast surgery performed after NAT does not reflect tumour response, resulting in potentially unnecessary radical surgery, especially mastectomy. The barriers to maximizing the surgical benefits of NAT need to be better understood and explored.

Multicentre study evaluating the surgical learning curve for posterior retroperitoneoscopic adrenalectomy.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy has gained international popularity in the past decade. Despite major advantages, including shorter duration of operation, minimal blood loss and decreased postoperative pain, many surgeons still prefer laparoscopic transperitoneal adrenalectomy. It is likely that the unfamiliar anatomical environment, smaller working space and long learning curve impede implementation. The present study assessed the number of procedures required to fulfil the surgical learning curve for posterior retroperitoneoscopic adrenalectomy. METHODS: The first consecutive posterior retroperitoneoscopic adrenalectomies performed by four surgical teams from university centres in three different countries were analysed. The primary outcome measure was duration of operation. Secondary outcomes were conversion to an open or laparoscopic transperitoneal approach, complications and recovery time. The learning curve cumulative sum (LC-CUSUM) was used to assess the learning curves for each surgical team. RESULTS: A total of 181 surgical procedures performed by four surgical teams were analysed. The median age of the patients was 57 (range 15-84) years and 61·3 per cent were female. Median tumour size was 25 (range 4-85) mm. There were no significant differences in patient characteristics and tumour size between the teams. The median duration of operation was 89 (range 29-265) min. There were 35 perioperative and postoperative complications among the 181 patients (18·8 per cent); 17 of 27 postoperative complications were grade 1. A total of nine conversions to open procedures (5·0 per cent) were observed. The LC-CUSUM analysis showed that competency was achieved after a range of 24-42 procedures. CONCLUSION: In specialized endocrine surgical centres between 24 and 42 procedures are required to fulfil the entire surgical learning curve for the posterior retroperitoneoscopic adrenalectomy.

Clinical signs of fibrosis in small intestinal neuroendocrine tumours.

BACKGROUND: In patients with small intestinal neuroendocrine tumours (SI-NETs), serotonin and other cytokines released from tumour cells may induce fibrosis, leading to carcinoid heart disease and abdominal fibrotic reactions. The aim of this study was to assess the prevalence, clinical complications and management of this reaction in the abdomen. METHODS: This was a retrospective cohort study of patients with SI-NETs diagnosed between 1985 and 2015. Clinical data, outcomes, radiological findings, and surgical and radiological interventions were reviewed. RESULTS: A total of 824 patients were diagnosed with SI-NETs in the study interval. Clinically significant abdominal signs and symptoms of fibrosis occurred in 36 patients. Of these, 20 had critically symptomatic central mesenteric fibrosis causing obstruction of mesenteric vessels, and 16 had retroperitoneal fibrosis causing obstructive uropathy with hydronephrosis. Extensive fibrosis causing mesenteric vessel obstruction and/or obstructive uropathy was more often associated with symptomatic and advanced disease encompassing lymph node metastases in the mesenteric root, para-aortic lymph node metastases, as well as liver metastases and peritoneal carcinomatosis. Palliative intervention in terms of superior mesenteric vein stenting or resection of central mesenteric metastases and/or percutaneous nephrostomy and J stent treatment was beneficial in the majority of the patients. CONCLUSION: Extensive abdominal fibrosis associated with clinically significant symptoms of intestinal ischaemia and/or obstructive uropathy was linked to advanced disease in patients with SI-NETs. Prompt recognition and minimally invasive intervention was effective in disease palliation.

Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles is a novel method in breast cancer. Several studies have verified the non-inferiority of SPIO compared with the standard use of radioisotope 99m Tc with or without blue dye. The aim of the MONOS study presented here was to evaluate the use of SPIO as a sole tracer and the efficacy of tracer injection in the preoperative setting. METHODS: This prospective cohort study was carried out in two hospitals, one using 99m Tc and the other SPIO. 99m Tc was injected in the morning of the day of surgery or the day before. SPIO was either injected before surgery in the outpatient clinic or 1 h before the operation. RESULTS: A total of 338 consecutive patients with breast cancer underwent 343 procedures; SPIO nanoparticles were used in 184 procedures and 99m Tc-labelled tracer in 159. Detection rates for SPIO and 99m Tc were 95·6 and 96·9 per cent respectively (P = 0·537). All nodes with SPIO uptake were coloured brown. Fewer nodes were retrieved with SPIO (mean 1·35 versus 1·89), regardless of whether blue dye was used (P < 0·001). Preoperative SPIO injection (58·7 per cent of procedures), a median of 16 (range 2-27) days before the procedure, was associated with a better tracer-specific detection rate (95·3 versus 86 per cent; P = 0·031) and retrieval of more nodes (mean 1·43 versus 1·03; P < 0·001) than perioperative administration. Skin staining was present in 39·9 per cent of patients, and was related to breast-conserving surgery and periareolar injection. CONCLUSION: The use of SPIO alone is a safe alternative, with results comparable to those of the standard dual technique using 99m Tc and blue dye. The efficacy of injection in the preoperative setting simplifies logistics and improves performance. Skin staining can be prevented by a deeper peritumoral injection.

Text mining and word embedding for classification of decision making variables in breast cancer surgery.

INTRODUCTION: Decision making in surgical oncology of the breast has increased its complexity over the last twenty years. This Delphi survey investigates the opinion of an expert panel about the decision making process in surgical procedures on the breast for oncological purposes. METHODS: Twenty-seven experts were invited to partake into a Delphi Survey. At the first round they have been asked to provide a list of features involved in the decision making process (patient's characteristics; disease characteristics; surgical techniques, outcomes) and comment on it. Using text-mining techniques we extracted a list of mono-bi-trigrams potentially representative of decision drivers. A technique of "natural language processing" called Word2vec was used to validate changes to texts using synonyms and plesionyms. Word2Vec was also used to test the semantic relevance of n-grams within a corpus of knowledge made up of books edited by panel members. The final list of variables extracted was submitted to the judgement of the panel for final validation at the second round of the Delphi using closed ended questions. RESULTS: 52 features out of 59 have been approved by the panel. The overall consensus was 87.1% CONCLUSIONS: Text mining and natural language processing allowed the extraction of a number of decision drivers and outcomes as part of the decision making process in surgical oncology on the breast. This result was obtained transforming narrative texts into structured data. The high level of consensus among experts provided validation to this process.

Challenging the current norm: Does health related quality of life data from reference populations accurately reflect baseline values in breast cancer patients? An observational cohort study comparing EORTC QLQ-C30 scores between the general Swedish population and baseline scores in breast cancer patients.

BACKGROUND: Increased overall survival in breast cancer patients has led to a growing recognition of long-term effects of cancer treatment of patients' quality of life. Health related quality of life (HRQoL) data, as measured by patient reported outcome measures (PROMs), is increasingly incorporated into clinical practice and research. A commonly used method current available to interpret HRQoL PROMs data is by comparison to reference values, often obtained from sampling of the general population. The aim of this study was to assess whether HRQoL reference values derived from the general population are an accurate representation of the baseline values of an outpatient breast clinic population. METHODS: A prospective observational cohort study was conducted by obtaining EORTC QLQ-C30 values for all patients offered an appointment in the outpatient breast clinic. These results were then compared to published baseline values in the general Swedish population, matched by gender and age. RESULTS: 568 questionnaires were returned with a response rate of 81,1 %. The outpatient breast clinic cohort reported a higher grade of symptoms, lower function and lower quality of life compared to the equivalent reference population. CONCLUSION: This study challenges the assumption that the reference values accurately reflect those of the study population which clinicians and researchers need to account for in study design and clinical practice.

The prognostic and predictive impact of low estrogen receptor expression in early breast cancer: a systematic review and meta-analysis.

INTRODUCTION: Traditionally, estrogen receptor (ER)-positive breast cancer has been defined as tumors with ≥1% positive for ER. The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines recommend that tumors with ER expression of 1%-10% should be classified as ER-low-positive, recognizing the limited clinical evidence on the prognostic and predictive role of low ER expression. We aimed to investigate the predictive role of ER-low expression to neoadjuvant chemotherapy (NeoCT) and the prognostic significance of ER-low expressing breast tumors compared with ER-positive or ER-negative breast tumors. METHODS: A meta-analysis was conducted using the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines and eligible articles were identified on PubMed and ISI Web of Science databases. The primary outcome was pathologic complete response and secondary outcomes were disease-free survival (DFS) and overall survival (OS). Twelve retrospective cohort studies were included in the meta-analysis. NeoCT resulted in higher pathologic complete response among patients with ER-low expression compared with ER-positive and comparable to ER-negative. Patients with ER-low breast cancer had a statistically significant worse DFS and OS compared with patients with ER-positive breast cancer, whereas no difference in DFS or OS was observed between ER-low and ER-negative subgroups. DISCUSSION: The current evidence suggests that ER-low breast cancer has a more similar outcome to ER-negative than to ER-positive breast cancer in terms of DFS and OS. ER-low expression seems also to have a predictive role regarding NeoCT. Considering the certainty of current evidence categorized as low to moderate, our results urge the need for well-designed prospective studies investigating the molecular background and the most appropriate treatment strategy for ER-low expressing breast cancer.

Simplifying Logistics and Avoiding the Unnecessary in Patients With Breast Cancer Undergoing Sentinel Node Biopsy. A Prospective Feasibility Trial of the Preoperative Injection of Super Paramagnetic Iron Oxide Nanoparticles.

PURPOSE: Sentinel node is routinely localized with the intraoperative use of a radioactive tracer, involving challenging logistics. Super paramagnetic iron oxide nanoparticle is a non-radioactive tracer with comparable performance that could allow for preoperative localization, would simplify the procedure, and possibly be of value in axillary mapping before neoadjuvant treatment. The current trial aimed to determine the a priori hypothesis that the injection of super paramagnetic iron oxide nanoparticles in the preoperative period for the localization of the sentinel node is feasible. METHODS: This is a prospective feasibility trial, conducted from 9 September 2014 to 22 October 2014 at Uppsala University Hospital. In all, 12 consecutive patients with primary breast cancer planned for resection of the primary and sentinel node biopsy were recruited. Super paramagnetic iron oxide nanoparticles were injected in the preoperative visit in the outpatient clinic. The radioactive tracer (99mTc) and the blue dye were injected perioperatively in standard fashion. A volunteer was injected with super paramagnetic iron oxide nanoparticles to follow the decline in the magnetic signal in the sentinel node over time. The primary outcome was successful sentinel node detection. RESULTS: Super paramagnetic iron oxide nanoparticles' detection after preoperative injection (3-15 days) was successful in all cases (100%). In the volunteer, axillary signal was presented for 4 weeks. No adverse effects were noted. Conclusion and relevance: Preoperative super paramagnetic iron oxide nanoparticles' injection is feasible and leads to successful detection of the sentinel node. That may lead to simplified logistics as well as the identification, sampling, and marking of the sentinel node in patients planned for neoadjuvant treatment.

Anal canal gastrointestinal stromal tumors - report of a rare case and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are considered as rare gastrointestinal tumors, and their location in the anal track is exceptionally unusual. We describe the case of a 28-year-old man with anal GIST, and a review of the cases that have been reported so far in the literature. CASE REPORT: The patient was referred for treatment of a gradually enlarging perianal mass. Clinical examination and imaging including orthosigmoidoscopy, transanal ultrasound, and magnetic resonance imaging (MRI) revealed a mass sized 7.5 cm in greatest diameter, in relation with the sphincters, which was excised under general anesthesia. His postoperative course was uneventful and he was discharged on the fourth postoperative day. Pathologic examination revealed characteristics of anal GISTs and further treatment with tyrosine kinase inhibitors was planned. CONCLUSION: Anal GISTs usually present with rectal bleeding and pain, and only sixteen cases have been reported in the literature. MRI is the radiologic examination of choice, while optimal treatment is considered surgery in combination with adjuvant therapy. Long-term follow-up is necessary. Hippokratia 2016, 20(4): 313-316.

Simultaneous pancreas-kidney transplantation: initial results from a center in Greece.

AIM: The outcome of simultaneous pancreas-kidney transplantation (SPK) in type 1 diabetes has dramatically improved in recent years. We report the initial results of our SPK program. PATIENTS AND METHODS: From 2008 to 2010, we performed and prospectively obtained data on 4 SPKs in 4 type 1 diabetic patients with chronic renal failure. The recipients were 3 men and 1 woman, of overall mean age of 40.75 ± 4.78 years, mean time from diabetes diagnosis of 27 ± 15 years, and time on dialysis of 3.5 ± 0.57 years. All grafts were procured from multiorgan brain-dead donors of mean age 26 ± 8.16 years and mean body weight of 74 ± 4.34 kg. The pancreatic grafts were transplanted first into the right iliac fossa with mean cold ischemia times of 10.62 ± 3.09 hours for the pancreatic and 14.00 ± 2.97 hours for the renal grafts. Pancreas arterial inflow was re-established by an end-to-side anastomosis of an extension Y-graft to the recipient right iliac artery. The portal vein was sutured to the iliac vein directly. The exocrine secretions of the pancreas were managed by duodenojejunostomy extraperitoneally (n = 3) or intraperitoneally (n = 1). The ureteral anastomosis was performed using the Taguchi technique. RESULTS: After SPK, endocrine pancreatic function was immediately restored in all patients. Insulin administration was stopped within the first 24 hours after surgery. Two patients displayed delayed renal graft function necessitating dialysis for 9 and 23 days, respectively. The postoperative course was prolonged with a mean hospital stay of 82 ± 1 day. At a 31.75 ± 9.03 months follow up all patients are alive with functioning grafts. CONCLUSION: Our experience with SPK, although limited, has shown encouraging results over a short follow-up period.

Hepatic artery thrombosis after orthotopic liver transplantation: 3 patients with collateral formation and conservative treatment.

Hepatic artery thrombosis (HAT), a serious complication after orthotopic liver transplantation (OLT), can lead to patient death in the absence of revascularization or retransplantation. Herein we have presented clinical characteristics, imaging findings, and long-term outcomes of 3 OLT patients with HAT who were treated conservatively and developed hepatic arterial collaterals. These patients underwent transplantation due to hepatitis B cirrhosis, cryptogenic cirrhosis, or hepatitis C infection and alcoholic disease. They presented with bile duct stenosis and/or a bile leak at 1, 3, and 36 months after transplantation, respectively, and were treated with percutaneous drainage and stent placement, endoscopic retrograde cholangio-pancreatography (ERCP), or reanastomosis of the bile duct over a T tube. HAT was confirmed using multidetector computed tomography (MDCT) 3-dimensional (3D) angiography and Doppler sonography. They survive in good condition with normal liver function at 30, 50, and 42 months after OLT, respectively. Development of collateral arterial circulation to the liver graft was detected with MDCT 3D angiography and Doppler sonography. From our experience with 3 patients and a literature review, we believe that there are a number of patients who experience long-term survival after the diagnosis of irreversible HAT and the development of collaterals. Although this group is at high risk for sepsis and biliary complications, these are usually self-limiting complications due to improved treatment regimens. The development of collateral arterial flow may also be beneficial.

Subcutaneous granular cell tumour of the lumbar region.

Granular cell tumour (GCT), also known as Abrikossoff tumour, is an uncommon neoplasm, probably of neural origin derived from Schwann cells. It usually presents as a subcutaneous solitary asymptomatic nodule. It has been the subject of much debate in the literature concerning the tumour origin and the association with other malignancies. We report a case of subcutaneous GCT in the lumbar region in a 31-year-old Caucasian male. Although they are a rare entity, GCTs should be considered in the differential diagnosis of the subcutaneous soft tissue tumours. Surgical removal with wide margins is the treatment of choice as malignant changes have been reported after long-term follow-up.

Tumour marker prescriptions for cancer screening in the Hellenic primary care.

Tumour markers are neither sensitive nor specific enough for cancer screening. Despite established guidelines, tumour marker 'screening myth' may be alive among physicians, but no study has analysed the phenomenon. This study aims to investigate tumour marker recommendation for screening purposes in primary care setting. A total of 209 Hellenic physicians were surveyed for screening activities by a multiple-choice questionnaire. Data were abstracted for the following tumour marker recommendations: carcinoembryonic antigen (CEA); cancer antigens 19.9, 125 and 15.3; alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG). A high rate of physicians advocate that tumour markers in cancer screening (range from 24% for beta-HCG to 46% for CEA). This phenomenon is not related to age, sex, type and level of physicians' specialization. In conclusion, many physicians recommend tumour markers for screening purposes. This may be harmful, since their prescriptions unnecessarily burden health economics, and further evaluation of false-positive findings might be associated with increased costs and risk from additional diagnostic/therapeutic interventions.

Epidemiology of ankylosing spondylitis in Northwest Greece, 1983-2002.

OBJECTIVE: To investigate the incidence and the prevalence of ankylosing spondylitis (AS) in a defined area of northwest Greece with a total population of about 500,000 inhabitants. METHODS: AS cases were recorded from (i) in- and out-patients referred to the rheumatology clinics of the Ioannina university hospital and the Ioannina general hospital, and (ii) patients referred to private rheumatologists practising in the study area. An incident case was defined as any patient with AS, diagnosed during the period between 1 January 1983 and 31 December 2002 who were resident in the study area for at least 1 yr before the diagnosis. A prevalent case was defined as any patient with AS who was a resident of the study area on 31 December 2002. Diagnosis was based on the modified New York criteria for AS. Population data were based on the 1981, 1991 and 2001 National Censuses. RESULTS: A total of 113 cases were diagnosed among the population of the area studied during the period 1983-2002. Men constituted a 4.65-fold higher number of patients than women, and had a significantly higher mean age at diagnosis. All patients presented bilateral sacroiliitis, 40 patients (35.9%) had peripheral joint involvement and 15 patients presented extra-articular manifestations (13.27%). HLA-B27 antigen was found in 80.5% of our patients. The age-adjusted mean annual incidence rate for the population aged > or =16 yr was 1.5 cases per 10(5) inhabitants [95% confidence interval (CI) 0.4-2.5], and the age-adjusted prevalence rate on 31 December 2002 was 29.5 cases per 10(5) inhabitants (95% CI 25.9-33.1). The incidence rates were higher in the age group 35-44 yr for men and in the age group 25-34 yr for women. CONCLUSION: The incidence and prevalence of AS in the area studied were significantly lower than in other white populations and higher than in the Japanese population.