Is axillary lymph node dissection necessary for positive preoperative aspiration cytology lymph node results?

INTRODUCTION: Based on international guidelines, axillary lymph node dissection (ALND) is recommended in cases of breast cancer if preoperative examinations confirm axillary metastasis. We examined which set of preoperative parameters might render ALND unnecessary. PATIENTS AND METHODS: Preoperative examinations (axillary ultrasound and aspiration cytology) confirmed axillary metastasis in 190 cases out of 2671 patients with breast cancer; primary ALN dissection was performed on these patients with or without prior neoadjuvant therapy. The clinicopathological results were analysed to determine which parameter might predict the presence of no more than 2 or 3 metastatic ALNs. RESULTS: The final histological examination confirmed 1-3 metastatic lymph nodes in ALND samples in 116 cases and over 3 metastatic lymph nodes in 74 cases. For patients receiving neoadjuvant therapy (59 out of the 190 cases), if the size of the primary tumour was 2 cm or smaller and/or the metastatic ALN was 15 mm or smaller, then the patient was likely to have no more than 3 positive ALNs (stage N0-1 disease) (p < 0.001). If the patient did not receive neoadjuvant therapy, stage N2 or N3 disease was very likely. No correlation was found between other clinicopathological characteristics of the tumour and involvement of the ALNs. CONCLUSION: Axillary lymph node dissection is not necessary for selected breast cancer patients with axillary metastasis receiving neoadjuvant therapy. In these cases, sentinel lymph node biopsy with or without radiation therapy and close follow-up may serve as adequate therapy.

Sentinel lymph node biopsy following previous axillary surgery in recurrent breast cancer.

INTRODUCTION: Ipsilateral breast recurrence or second primary breast cancer can develop in patients who have undergone breast conserving surgery (BCS) and axillary surgery. The purpose of this study was to examine the feasibility of a reoperative sentinel lymph node biopsy (SLNB) as a repeated axillary staging procedure. PATIENTS AND METHODS: From August 2014 through January 2017 patients with locally recurrent breast cancer or with BRCA mutation requiring risk reduction mastectomy as a second surgical procedure, underwent repeat SLNB in three Hungarian Breast Units with a radiocolloid (and blue dye) technique. RESULTS: Hundred and sixty repeat SLNBs were analysed, 80 after previous SLNB and 80 after previous total or partial axillary lymph node dissection (ALND). SLN identification was successful in 106 patients (66%); 77/80 (77.5%) and 44/80 (55%) in the SLNB and ALND groups, respectively. (p < 0.003). Extra-axillary lymph drainage was more frequent in the ALND group (19/44, 43,2% versus 7/62, 11,3%; p < 0.001). Lymphatic drainage to the contralateral axilla was observed in 14 patients (11 in the ALND group, p = 0.025), isolated parasternal drainage was detected in 4 patients (p = 0.31). Only 9/106 patients with successful repeat SLNB (8,8%, all with 1 SLN removed) had SLN metastases CONCLUSIONS: Repeat SLNB is feasible in patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous BCS and axillary staging. Repeat SLNB should replace routine ALND as the standard axillary restaging procedure in recurrent disease with a clinically negative axilla. Preoperative lymphoscintigraphy is important to explore extra-axillary lymphatic drainage in this restaging setting.

Unifocal, multifocal and diffuse carcinomas: a reproducibility study of breast cancer distribution.

Multifocality of invasive breast carcinoma has been associated with prognostic disadvantage. Unifocal, multifocal and diffuse distributions have been recently defined for both inasive carcinomas and in situ components, and these have been combined into categories of prognostic relevance. Eight observers analyzed the same series of 30 megaslides from 29 carcinomas, and had to classify the lesions into the three distribution patterns of unifocal, multifocal or diffuse (or not present/non influential). The reproducibility of the distribution patterns of invasive carcinomas was better than that of the in situ carcinoma components, but was still only fair to moderate on the basis of kappa values. The reproducibility of DCIS was poor to slight with some kappa values reflecting agreement by chance only. The results suggest the definitions of these distribution patterns require refinements for a more reliable and reproducible diagnosis if one wants to associate prognostic information with this variable.

The relationship of multifocality and tumor burden with various tumor characteristics and survival in early breast cancer.

The presence of multifocality and the aggregate tumor size were retrospectively analysed in a database of 1071 operated breast cancers. Around a quarter of all these cancers involved multiple foci, while a tenth of the total demonstrated more than one invasive focus. Although the multifocal cancers were smaller and more often screen-detected than the unifocal cancers, their aggregate tumor size was larger, and they more frequently displayed casting-type calcifications in the mammogram and HER2 positivity. Lobular histology favoured larger tumor burden. The invasive multifocal cancers were more commonly lymph node-positive than the other tumors. In a subgroup of 584 patients with a median follow-up time of 5 years, the larger size of the invasive tumor, the presence of LVI or lymph node involvement, HER2 positivity and triple negativity were associated with a poorer RFS and OS, while the outcome of screen-detected tumors was superior to that of non-screen-detected or interval cancers. A large tumor size, lymph node positivity and HER2 positive or triple negative phenotypes were independent determinants of a poorer survival rate.

Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer.

Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.

Identification of virus resistant tumor cell subpopulations in three-dimensional uveal melanoma cultures.

To better understand melanoma resistance to herpes simplex virus type 1 (HSV-1)-mediated oncolysis, traditional two-dimensional (2D) cultures and extracellular matrix (ECM) containing three-dimensional (3D) cultures of OCM1 and C918 uveal melanoma cells were infected with an HSV-1 strain that expresses the green fluorescent protein (GFP) marker during replication. Although 2D cultures were completely destroyed within a few days of HSV-1 inoculation, viable GFP-negative tumor cells remained detectable in 3D cultures for several weeks. Tumor cells with increased resistance to HSV-1 included cells that formed vasculogenic mimicry patterns and multicellular spheroids and cells that invaded Matrigel individually. Mechanisms of tumor resistance against HSV-1 in the 3D environment included impaired virus spread in the ECM and ECM-mediated inhibition of viral replication after viral entry into tumor cells. Observations also suggested that HSV-1 established quiescent infection in some tumor cells present in multicellular spheroids and that this could revert to productive viral infection when the tumor growth pattern changed. These findings indicate that 3D tumor cell cultures can be used to identify distinct tumor cell populations with increased resistance to HSV-1 and to explore mechanisms of ECM-mediated tumor resistance to oncolytic virotherapy.

Changes in faecal bacteria associated with concentrate and forage-only diets fed to horses in training.

REASONS FOR PERFORMING STUDY: Diets rich in readily fermentable carbohydrates, fed traditionally to meet the increased energy requirements of the performance horse, are associated with a number of gastrointestinal disorders that involve disturbances in the intestinal microbiota, however, these changes are poorly understood. OBJECTIVES: With the long-term objective of improving intestinal health and to increase understanding of the relationship between diet and microbiota, the effect of feeding Standardbred horses a high-energy forage-only (F) diet was studied compared to a more traditional forage-concentrate (C) diet on faecal microbiota. METHODS: Diets were fed in a cross-over design to 6 mature geldings on a scheduled training regime, both periods consisting of 29 days. DNA was extracted from faecal samples collected at 4 time points from each period, bacterial 16S rRNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing. Faecal pH and cultivable lactic acid bacteria (LAB) and enterobacteria were also assessed on the final collection day of each period. RESULTS: Diet F resulted in a microbial composition that was more stable between sampling periods and had lower counts (P < 0.05) of cultivable LAB and specifically members of the Streptococcus bovislequinus complex. Motile and swarming Lactobacillus ruminis was present in all horses on diet C and not in horses on diet F. Diet C also resulted in the increase (P < 0.05) in members of Clostridiaceae cluster III and a concomitant reduction (P < 0.05) in an unknown group of Bacteroidales. CONCLUSIONS AND POTENTIAL RELEVANCE: The greater microbial stability and reduction in LAB and members of the Streptococcus bovis/equinus complex on diet F indicate an opportunity to develop feeding strategies that support equine health and welfare. Novel changes identified in the faecal microbiota that resulted from carbohydrate inclusion merit further investigation.

Esophageal intramural metastasis from adenocarcinoma of the gastroesophageal junction.

Among a total of 143 patients examined for diagnosis of adenocarcinoma of the cardia, intramural esophageal metastases were verified in six patients (4.19 %). In each case the diagnosis was confirmed by histological examination. The histological structure of the primary tumors and metastases was the same. Metastases were detected by endoscopic ultrasound examination in three cases. All the cardia tumors proved to be well advanced. As well as endoscopic identification of the primary tumor, thorough examination of the proximal part of the esophagus is of great importance.

[What kind of surgical radicality is justified in the treatment of esophageal and cardial carcinoma?]. / Wie radikal soll das Osophagus- bzw. Kardiakarzinom operiert werden?

In the period from January 1, 1973 to November 30, 1994, a total number of 1 856 patients had been admitted to our Department of Surgery because of cancer of the esophagus and esophago-gastric junction. We divided our activities into two study periods. In the first study period from 1973 to 1984 only so called "conventional operations" were performed. Since 1985 new oncological aspects were introduced into our operative tactics:1. the subtotal esophagectomy combined with the two-field lymphadenectomy,2. the total gastrectomy with extended lymph node dissection. The analysis of our results with respect to the survival parameters (TNM staging, histological type, grade of differentiation, gross pathology) showed that the best chances were obtained by curative resection and lymphadenectomy in tumours of low-grade biologic malignancy. In esophageal cancers the former 6 % 5-year cumulative survival rate increased to 26 %, and in cardia tumours from 9 to 27 %, because of enhancement of radicality and extension of lymphadenectomy.

[Esophageal anastomosis--based on the experience with 1460 operations]. / Nyelócsó anasztomózisokról: 1460 mútét tapasztalata alapján.

The authors reviewed the clinical records of 1460 patients with esophageal anastomoses, the operations performed in their institute between 1973 and 2000. Surgical outcome was assessed with incidence of anastomotic leaks and overall mortality. Hand-sewn anastomoses were performed by inserting single layer interrupted monofil steel wire (507), PDS (232) or Vicryl (65) sutures and circular stapler (EEA, Ethicon) was used in 656 patients. 453 (65 cervical, 293 thoracic, and 95 abdominal) anastomoses performed between 1995 and 2000 were analyzed separately. During this 6-year period, the majority of operations (88%) were performed because of esophageal malignancy (squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia). Surgery was performed for benign disease (e.g. stricture, perforation, and stage IV achalasia) in 12%. The incidence of anastomotic leak was the highest (20%) after cervical anastomosis, compared to a 4.4% or 1% associated with thoracic or abdominal anastomoses. These differences are statistically significant (p < 0.001). The rate of anastomotic leakage was strongly connected to surgical technique: it was 15% in hand-sewn anastomoses and only 4.4% with stapled anastomosis. During the 6-year period overall mortality was 6.6%t.

[Siewert-Stein classification of adenocarcinoma of the esophagogastric junction]. / Az oesophagogastricus junctio adenocarcinomáinak Siewert-Stein klasszifikációjáról.

Nowadays the terminology used for the definition of adenocarcinomas at the oesophagogastric junction is "cardiac carcinoma", which can be easily misunderstood. This definition of adenocarcinomas of the oesophagogastric junction does not allow correct comparison of diagnosis (endoscopic, radiological and pathologic), epidemiology and surgical therapy in national and international aspects, because different tumours can develope in the same area, and all called cardia tumors. Siewert and Stein recommended a classification to solve this problem. The classification of the tumours is morphological/topographical. Type I is adenocarcinoma of the distal part of the oesophagus. Type II is adenocarcinoma of the real cardia and type III is subcardial gastric adenocarcinoma. At classification, we always consider results of endoscopy (ortograde and retroflexed view of the oesophago-gastric junction), the x-rays of the oesophagus and stomach, findings at the operation and pathohistologic results. Between 1/1/1974 and 31/12/2000, a total number of 50,878 upper panendoscopic examinations were performed at the Endoscopic Laboratory of the Surgical Department. Adenocarcinoma of the cardia was diagnosed in 488 patients. According to the Siewert-Stein classification, type I tumour was found in 123 (25.2%), type II in 240 (49.18%), and type III was present in 125 (25.61%) patients. The importance of this classification is it enables unified pre-operative assessment and it can also help to decide the type of the surgical intervention. In our patients with type I cancer--depending of the size of the tumour--distal 2/3 oesophagectomy with the resection of the proximal lesser curve of the stomach or total gastrectomy were performed. In the first group oesophago-jejuno-gastrostomy, in case of total gastrectomy Roux-en-Y loop anastomosis was created. In patients with types II and III cancers total gastrectomy was performed. In every patient lymphadenectomy was performed. We suggest the use of this new classification in clinical, gastroenterology--with special regard to the endoscopy--and pathology.

[Laparoscopic adrenalectomy with transperitoneal approach]. / Laparoszkópos adrenalektómia transzperitonealis módszerrel.

UNLABELLED: The feasibility, safety, and results of 52 laparoscopic transperitoneal adrenalectomies were evaluated. METHODS: A total of 52 patients were included in the study based on thorough endocrinological and imaging assessment. 15 patients with Conn syndrome, 3 with Cushing syndrome, 15 with nonfunctioning adenoma, 14 with pheochromocytoma, 2 with adrenocortical cyst, 2 with adrenocortical lipoma and 1 with metastasis were considered eligible for adrenalectomy. Lesion size ranged from 1 to 12 cm (mean 4.53 cm). Concurrent surgical procedures were performed in 6 patients (11%). RESULTS: There was one conversion (during a left adrenalectomy), because of our learning curve. After we changed the technique, there was no more conversion. There were two (3.8%) postoperative complications: postoperative pancreatitis, one of the patients required re-operation (lavage and drainage). There was one wound infection. We had no postoperative mortality. Mean postoperative hospital stay was 6 days (range, 2-27 days). CONCLUSION: Patients with secreting and non-secreting adrenal lesions can be treated safely and effectively by laparoscopic adrenalectomy.

[Rare late complication after subtotal esophagectomy]. / Nyelócsórezekció után kialakult ritka késói szövódmény.

We report a case of a peptic ulcer developed in the stomach tube used for the replacement of the esophagus. The patient was a 60 years old female who had undergone subtotal esophagectomy for mid esophageal malignancy, with intrapleural stomach replacement. Urgent endoscopy revealed an excavated, bleeding ulcer in the thoracic part of the stomach. After unsuccessful medical treatment urgent operation was performed via right thoracotomy. Opening the stomach an ulcer was found on the posterior wall of the stomach, it was penetrating to the right atrium of the heart. The bleeding was controlled by suturing the atrium wall. The patient treated with i.v. Omeprazol in the postoperative period. On the 21st postoperative day a rebleeding occurred causing shock. After reoperation the patient died. This complication is very rare. We emphasise the importance of postoperative pH measurement investigations showing the presence of duodenogastric reflux disease.

[Isolated gastroduodenal Crohn's disease: a case report]. / Izolált gasztroduodenális Crohn betegség: esetismertetés.

Although it can involve any segment of the gastrointestinal tract, Crohn's disease confined to the gastroduodenum is extremely rare. We report the story of a 20-years old male patient admitted for pyloric obstruction that developed despite medical treatment. Clinical manifestations necessitated operative treatment; Polya-gastrectomy was performed. Histology identified Crohn's disease and inflammatory changes as the cause of pyloric obstruction. Postoperative recovery was uneventful. The lesson of this case is, that if duodenal Crohn's disease would have been recognized preoperatively, gastrectomy could have been avoided. We review the literature and discuss treatment options for gastroduodenal Crohn's disease.

Trace formula for noise corrections to trace formulas.

We consider an evolution operator for a discrete Langevin equation with a strongly hyperbolic classical dynamics and Gaussian noise. Using an integral representation of the evolution operator L, we investigate the high-order corrections to the trace of L(n). The asymptotic behavior is found to be controlled by subdominant saddle points previously neglected in the perturbative expansion. We show that a trace formula can be derived to describe the high-order noise corrections.

Percutaneous video choledochoscopic treatment of retained biliary stones via dilated T-tube tract.

BACKGROUND: Retained biliary stones is a common clinical problem in patients after surgery for complicated gallstone disease. When postoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy are unsuccessful, several percutaneous procedures for stone removal can be applied as alternatives to relaparotomy. These procedures are performed either under fluoroscopic control or with the use of choledochoscopy, but it is also possible to combine these methods. METHODS: Since 1994, we have used the percutaneous video choledochoscopic technique for the removal of difficult retained biliary stones via dilated T-tube tract in 17 patients, applying the technique of percutaneous stone extraction used in urology. While waiting for the T-tube tract to mature and after the removal of the T-tube, the dilatation of its tract was 26-30 Fr. Stone removal was carried out using a flexible video choledochoscope and a rigid renoscope under fluoroscopic control, with the aid of Dormia baskets, rigid forceps, and high-pressure irrigation. RESULTS: We performed 23 operative procedures, and the clearance of the biliary ducts was successful in all cases. There were no major complications or deaths. CONCLUSION: Percutaneous video choledochoscopic-assisted removal of large retained biliary stones via the T-tube tract is a highly effective and safe procedure. Its advantages over other procedures include the ability to visualize the stones and noncalculous filling defects; it also guarantees that the stones can be removed under visual video endoscopic control. It has no problems related to tract or stone size.

[Esophageal implantation metastasis from adenocarcinoma of the cardia]. / Kardia adenokarcinóma implantációs metasztázisa a nyelócsóben.

A 74 years old male patient was admitted to our department suffering from dysphagia for five months. Gastric Barium studies showed a cardia tumour with polypoid lesions in the wall of the esophagus, and gastro-esophageal reflux disease was also diagnosed. Endoscopy verified a cardia tumour with esophageal metastasis, and biopsy was obtained from the two lesions. Histology showed that both tumours were adenocarcinomas. Endoscopic ultrasonography classified the cardia tumour as grade T2. As observed during endoscopy, the wall of the esophagus at the level of the polypoid lesion was hypo-echogenic and thick which was result of thickened mucosa. Total gastrectomy and oesophagectomy was performed. Pathology showed that the cardia tumour was pT2N2 and type Siewert-Stein II. The esophageal polypoid lesion was also proved an adenocarcinoma, which was localized only to the mucosa. No tumour cells were found in the blood- or in lymph vessels between the tumour and the esophageal adenocarcinoma. We think that the polypoid adenocarcinoma in the esophagus is an esophageal metastasis implantation from the cardia adenocarcinoma. It is based on the exclusion of other possible tumour dissemination routes. Probably the gastro-esophageal reflux is responsible for the implantation of tumour cells.

Changes of serum calcium level following thyroid surgery--reasons and clinical implications.

The reasons of transient hypocalcemia, frequently occurring after thyroid surgery, were investigated. Serum total calcium (seCa) and phosphorus (seP) levels were determined in 185 patients with benign nodular goiter before and after thyroid surgery. Beside these, in 27 additional patients, serum magnesium (seMg), total protein, albumin, calcitonin, parathormone (PTH) and 25-OH-D3 vitamin (25-OH-D3) levels were determined; corrected calcium (cCa) values, reflecting ionized calcium concentrations, were calculated. The daily changes of seCa and protein levels were measured in 20 patients. Another twenty patients, undergoing non-endocrinological surgery served as controls. Transient, mild but significant decrease of seCa was observed after surgery, while seP values were increased. Mild hypocalcemia (seCa<2.12 mmol/l) developed in 18.4%, severe hypo-calcemia (seCa<1.9 mmol/l) in 5.4% of the patients. The reduction of seCa levels was more pronounced in elderly, female patients. SeMg, total protein and albumin decreased, while cCa, PTH, calcitonin and 25-OH-D3 values did not change. Positive correlation was demonstrated between the change of seCa and albumin levels. Similar results were obtained in the general surgery group. In the thyroid operated group, in case of severe hypocalcemia, PTH levels decreased significantly into the pathological range. It may be concluded that transient, mild postoperative hypocalcemia is not a thyroid surgery-dependent phenomenon; it can also be observed after other operations accompanied by similar blood loss; in its development hypoalbuminemia plays a role. The causal role of PTH, calcitonin and 25-OH-D3 could not be proved in this study. Hypoparathyroidism can be responsible for the development of severe, prolonged hypocalcemia occurring at rare occasions.

Microsatellite single nucleotide polymorphisms in the HLA-DQ region.

Sequencing studies were performed in three previously described microsatellite and minisatellite markers located within the HLA-DQ region, DQCAR, DQCARII and G51152. Multiple nucleotide substitutions that did not change size polymorphisms were observed in all three markers. In all loci, the number of core repeats did not correlate with neighboring DQ allele sequence motifs while single nucleotide changes within or flanking the microsatellite sequence did. This result indicates higher mutation rates for microsatellite expansions/contractions than for nucleotide substitutions in these loci. Further analysis indicated an almost complete phylogenetic correspondence between DQCAR single nucleotide polymorphisms (SNPs) and DQB1 sequences on one side (1.0-1.5 kb apart) and a complete relationship between DQCARII and DQA1 sequences on the other (4.5 kb apart). In contrast, G51152 sequences did not correspond perfectly with DQB1 allelic sequences, thus suggesting the existence of several ancestral crossovers between this marker and DQB1 (20-25 kb). Sequencing microsatellites might be useful in disease mapping studies by increasing marker informativeness and by helping in the interpretation of association study results. It is also proposed that SNPs within the flanking region of CA repeats could be used to develop biallelic markers from already available mapped microsatellite markers.

The role of esophagectomy in the management of esophageal perforations.

BACKGROUND: Despite the many advancements made in thoracic surgery, the management of patients with esophageal perforation remains problematic and controversial. METHODS: Between 1985 and 1995, 27 esophagectomies were performed for perforation of the thoracic esophagus. A retrospective review of the records of these patients was carried out, and a scoring scale developed by Elebute and Stoner to grade the severity of sepsis was applied. RESULTS: Among the 27 patients undergoing esophagectomy for a perforation, the interval between rupture and esophagectomy was less than 24 hours in only 11 patients (40.7%). Postoperative surgical complications occurred in 4 patients (14.8%) and nonsurgical complications, in 7 (25.9%). The hospital mortality rate was 3.7% (1/27). In 14 patients, primary reconstruction was performed in the bed of the excised esophagus. There were no anastomotic leaks in this subgroup. This suggests that an anastomosis between viable, well-vascularized tissues is more important for successful healing than avoidance of some degree of contamination of the adjacent mediastinum. On follow-up, which averages 41 months, 73% of patients (16/22) have neither symptoms nor complaints. CONCLUSIONS: Esophageal resection definitively eliminates the source of intrathoracic sepsis, the perforation, and the affected esophagus. Reconstruction carried out in one stage does not increase operative morbidity. Esophageal resection and reconstruction is a valid approach even in cases of spontaneous perforation in which the diagnosis is markedly delayed.