The relationship between IL-6 and thrombocytosis accompanying gastrointestinal tumours.

INTRODUCTION: Several reports have stated that thrombocytosis is associated with worse survival and higher rate of metastasis in solid tumours. A study in ovarian tumours implicated IL-6 produced by tumour cells as a key mechanistic factor. AIM: To evaluate the relevance of this paraneoplastic pathway in gastrointestinal cancer. MATERIAL AND METHODS: After excluding thromboembolic and inflammatory disorders, 161 patients were enrolled who had been operated due to various gastrointestinal cancer at the 1st Department of Surgery at the Semmelweis University between 2015 and 2017. Platelet counts and serum IL-6 levels were determined from preoperative blood samples. Thrombocytosis was defined as the upper limit of normal platelet count, e.g. 400 × 103/µl. RESULTS: A weak but significantly positive correlation was found between elevated platelet counts and serum IL-6 (correlation coefficient: R = 0.214, p = 0.006), which became more pronounced in colon and oesophageal cancer if evaluated in the different tumour types (R = 0.292 and R = 0.419, respectively). However, using a multivariant linear regression model (R 2 = 0.47) corrected with haemoglobin, white blood cell count, and advanced disease stage, the analysis showed no significant correlation between serum IL-6 and platelet counts. CONCLUSIONS: In gastrointestinal cancer our study did not support the paracrine-mediated paraneoplastic pathway described in ovarian tumors. Thrombocytosis showed significant correlation with white blood cells instead of serum IL-6, which implies that the inflammatory process may influence both parameters. Further studies are needed on larger patient cohorts.

[Guidance for transanal operations]. / Transzanális mutéti útmutató.

We summarized diagnostic, surgical treatment and follow-up principles of benign and early malignant lesions of the rectum. Our aim is to provide a nationwide practical synopsis of transanal minimally invasive surgical techniques which might be the basis of a Hungarian national audit of rectal polyp management.

[Diverticulosis and diverticulitis of the vermiform appendix. Report of a case and review of the literature]. / A féregnyúlvány diverticulosisa, diverticulitise. Esetismertetés és irodalmi áttekintés.

Diverticulitis of the vermiform appendix is a rare disease with clinical features often similar to conventional acute appendicitis. The importance of appendiceal diverticulosis is the fact that it can lead to an early and a higher incidence of perforation and therefore a higher mortality rate, in contrast to acute appendicitis alone. In this study we present the clinicopathology, diagnosis and therapy of the disease with a review of the literature. A 65-year-old woman presented to the emergency department with a 48-hour history of intermittent pain in the right iliac fossa. Abdominal ultrasound raised the possibility of acute appendicitis but because of the relative asymptomatic state of the patient, the lack of fever and rebound tenderness we started observation. After 2 days with episodic abdominal pain, the patient was taken to the operating theatre for laparoscopic exploration. Intraoperatively, multiple diverticula were noted on the appendix and appendectomy was performed. Histopathological examination revealed diverticulosis and inflammation of the appendiceal wall. Due to the possible complications, the difficult preoperative diagnosis and its frequent association with appendiceal neoplasm, appendiceal diverticulosis requires special attention. For asymptomatic cases, incidentally diagnosed intraoperatively or discovered by radiology prophylactic appendectomy is recommended. Orv Hetil. 2018; 159(19): 768-772.

Successful treatment of three synchronous primary malignant tumours-reflection on surgical, pathological and oncological aspects and decision making.

We report a case of a patient with triple synchronous primary malignancies (breast, colon, kidney) which has not been previously reported in the literature. A 70-year-old woman was diagnosed with invasive ductal carcinoma of the left breast with axillary lymph node metastasis. During the staging period, renal cell carcinoma on the left kidney and mucinous adenocarcinoma in the proximal colon were found. Since the breast tumour demonstrated favourable biology, aromatase inhibitor therapy had been started and simultaneous right colectomy and left nephrectomy was performed. Six months after the first diagnosis, left sector excision and axillary block dissection were performed. Adjuvant FEC chemotherapy was administered, followed by radiotherapy. During the 16-month follow-up period disease recurrence was not detected.

Paraneoplastic thrombocytosis in gastrointestinal cancer.

It has been demonstrated recently in several solid tumors that thrombocytosis at diagnosis may correlate with tumor invasion, metastatic progression and worse outcome. Several details of the pathomechanism of the relationship of thrombocytosis and cancer have been elucidated; however, the complete process is not clearly understood. Several hypotheses have been proposed. Recently, it was suggested that in ovarian cancer elevated IL-6 production by the tumor may induce increased megakaryopoiesis via hepatic thrombopoietin production leading to thrombocytosis. The importance of the prognostic power of elevated platelet count is still debated in gastrointestinal cancer. The aims of this review were to evaluate the prognostic significance of thrombocytosis in gastrointestinal tumors, to see whether clinical practice confirmed the hypotheses and to reveal the causes of the inconsistent findings.

[A giant myxoid leiomyoma mimicking an inguinal hernia]. / Lágyéksérvet utánzó gigantikus méretu myxoid leiomyoma.

Leiomyoma is a rare, smooth muscle tumour that can occur everywhere in the human body. The authors present the history of a 60-year-old female, who had a giant, Mullerian type myxoid leiomyoma in the inguinal region mimicking acute abdominal symptoms. After examination the authors removed the soft tissue mass in the right femoral region reaching down in supine position to the middle third of the leg measuring 335 × 495 × 437 mm in greatest diameters in weight 33 kg. Reconstruction of the tissue defect was performed using oncoplastic guidelines. During the follow-up time no tumour recurrence was detected and the quality of life of the patient improved significantly.

Decreased functional activity of multidrug resistance protein in primary colorectal cancer.

BACKGROUND: The ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies. METHODS: 100 colorectal cancer and 28 adjacent healthy mucosa samples were obtained by intraoperative surgical sampling. Activity of MDR1 and MRP1 of viable epithelial and cancer cells were determined separately with the modified calcein-assay for multidrug resistance activity and sufficient data of 73 cancer and 11 healthy mucosa was analyzed statistically. RESULTS: Significantly decreased mean MDR1 activity was found in primary colorectal cancer samples compared to normal mucosa, while mean MRP1 activity showed no significant change. Functional activity was not affected by gender, age, stage or grade and localization of the tumor. CONCLUSION: We found lower MDR activity in cancer cells versus adjacent, apparently, healthy control tissue, thus, contrary to general belief, MDR activity seems not to play a major role in primary drug resistance, but might rather explain preferential/selective activity of Irinotecan and/or Oxaliplatin. Still, this picture might be more complex since chemotherapy by itself might alter MDR activity, and furthermore, today limited data is available about MDR activity of cancer stem cells in colorectal cancers. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1675739129145824.

Relationship of postoperative thrombocytosis and survival of patients with colorectal cancer.

INTRODUCTION: Thrombocytosis accompanying solid tumors and predicting the prognosis of malignant tumors has been the subject of intensive research lately. Reports so far have evaluated the role of preoperative platelet count. In our present study we looked at the effect of tumor removal on platelet count and the predictive power of postoperative thrombocytosis on the survival of patients with colorectal cancer (CRC). METHODS: We retrospectively evaluated the clinical and histopathological data of 336 patients operated due to CRC between 2001 and 2011. Thrombocytosis was defined as a platelet count exceeding 400 × 10(3)/µL. Preoperative platelet count was compared with the value measured 1 month postoperatively. RESULTS: The platelet count significantly decreased after the removal of the primary tumor (paired Wilcoxon test p < 0.001). In univariate analysis preoperative thrombocytosis was a significant marker of overall survival (OS) with HR 2.2, p < 0.001 while the postoperative thrombocytosis was nearly significant with HR = 1.59, p = 0.087. In multivariate setting, when corrected for location, stage, tumor size and controlling for gender and age (> 65 years vs. ≤ 65 years), both pre- and postoperative thrombocytosis were significant independent prognostic markers with HR 1.80, p = 0.20 and HR = 1.98, p = 0.018, respectively. DISCUSSION AND CONCLUSION: Although the pathomechanism of thrombocytosis related to solid tumors is not known the decrease of platelet count after the removal of the primary tumor raises the possibility that the tumor may play an active role in the development of thrombocytosis. Furthermore, the observation of postoperative thrombocytosis with significant worse outcome underlines the predictive power of elevated platelet count.

[Is it radical enough? Transanal endoscopic microsurgery for the treatment of rectal neoplasia -- clinicopathological viewpoint]. / Kelloen radikális? Transanalis endoscopos mikrosebészeti technika szerepe a rectum daganatainak ellátásában -- egy év tapasztalatainak klinikopatológiai értékelése.

The transanal endoscopic microsurgery (TEM) provides lower relapse and complication rate for the the surgical treatment of the neoplasms of the middle and lower third of the rectum in selected cases. Hence, it can be an alternative method of the conventional approaches, if it does not compromise oncological radicality. The TEM procedure has been started at the 1st Department of Surgery, Semmelweis University in the fall of 2013. In this short study we have evaluated the clinicopathological characteristics of patients undergoing TEM between September 2013 and September 2014. Fourty-four patients were included in our retrospective analysis. 12 patients had low grade adenoma, 14 patients had high grade adenoma, 17 patients had invasive adenocarcinoma, while one was operated for a neuroendocrine tumor. There was no difference in the size of neoplasms between the low and high grade adenomas or adenocarcinomas (p = 0.210), tumors below the size of 30 mm or over 30 mm displayed no significant difference either (p = 0.424). The surgical margins were free of tumor in 41 cases (95.3%). In 13 out of 44 cases the preoperative histology proposed a lower grade neoplasm than the final report (p < 0.001). These results demonstrate that the surgical treatment of large adenomas with TEM technique, which involves excision of the whole bowel wall, is more appropriate than the fractionated removal or polypectomy supplemented by mucosectomy. The pT2 stage tumours might be subjected to the TEM method in selected cases (e.g. following neoadjuvant treatment or palliative care), but this has to be confirmed with prospecively evaluated large series clinical studies which are currently ongoing.

[TEO: minimally invasive surgery of the rectum. A short review]. / TEO: Minimálisan invazív rectumsebészet. Rövid áttekintés.

The equipment and technique of transanal endoscopic microsurgery was developed by Buess in the early 80s. The technique was more refined, and the indication was widened since then. Excellent oncological results can be achieved with good patient selection with this less invasive technique and the complication rate is very low in contrast to conventional techniques. Nowadays the transanal endoscopic microsurgery is the "gold standard" in the treatment of benign lesions and low risk T1 cancer of the rectum.

Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging.

Negative ion desorption electrospray ionization (DESI) was used for the analysis of an ex vivo tissue sample set comprising primary colorectal adenocarcinoma samples and colorectal adenocarcinoma liver metastasis samples. Frozen sections (12 µm thick) were analyzed by means of DESI imaging mass spectrometry (IMS) with spatial resolution of 100 µm using a computer-controlled DESI imaging stage mounted on a high resolution Orbitrap mass spectrometer. DESI-IMS data were found to predominantly feature complex lipids, including phosphatidyl-inositols, phophatidyl-ethanolamines, phosphatidyl-serines, phosphatidyl-ethanolamine plasmalogens, phosphatidic acids, phosphatidyl-glycerols, ceramides, sphingolipids, and sulfatides among others. Molecular constituents were identified based on their exact mass and MS/MS fragmentation spectra. An identified set of molecules was found to be in good agreement with previously reported DESI imaging data. Different histological tissue types were found to yield characteristic mass spectrometric data in each individual section. Histological features were identified by comparison to hematoxylin-eosin stained neighboring sections. Ions specific to certain histological tissue types (connective tissue, smooth muscle, healthy mucosa, healthy liver parenchyma, and adenocarcinoma) were identified by semi-automated screening of data. While each section featured a number of tissue-specific species, no potential global biomarker was found in the full sample set for any of the tissue types. As an alternative approach, data were analyzed by principal component analysis (PCA) and linear discriminant analysis (LDA) which resulted in efficient separation of data points based on their histological types. A pixel-by-pixel tissue identification method was developed, featuring the PCA/LDA analysis of authentic data set, and localization of unknowns in the resulting 60D, histologically assigned LDA space. Novel approach was found to yield results which are in 95% agreement with the results of classical histology. KRAS mutation status was determined for each sample by standard molecular biology methods and a similar PCA/LDA approach was developed to assess the feasibility of the determination of this important parameter using solely DESI imaging data. Results showed that the mutant and wild-type samples fully separated. DESI-MS and molecular biology results were in agreement in 90% of the cases.

Expression of tight junction molecules in breast carcinomas analysed by array PCR and immunohistochemistry.

In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical phenotype as a surrogate for the genetic subtype, 11 luminal A, 3 luminal B, 3 triple negative and one HER2+ cases were included. Ten genes were significantly downregulated in tumors compared with normal breast tissues (CLDNs 5, 10, 16, 18, 19, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3), whereas one gene (CLDN17) was significantly up-regulated in tumors when compared with normal breast. At protein level CLDNs 5, 10, 16, 18, ZO-1 and ZO-2 were downregulated in tumors as compared with normal breast tissue. CLDN17 showed variable expression in tumor tissues in comparison to normal breast. In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated. We found altered TJ genes and proteins whose expression has not yet been associated with breast carcinoma. Our findings show a tendency of TJ genes and proteins to be downregulated in breast cancer. Further studies are necessary to examine whether the downregulation of the above mentioned TJ associated genes and proteins may contribute to the malignant progression of invasive ductal breast carcinomas.

[Therapy of radiation enteritis--current challenges]. / A radiogén enteritis kezelésének kihívásai napjainkban.

Radiation enteritis is one of the most feared complications after abdominal and pelvic radiation therapy. The incidence varies from 0.5 to 5%. It is not rare that the slowly progressing condition will be fatal. During a period of 13 years 24 patients were operated due to the complication of radiation enteritis. Despite different types of surgery repeated operation was required in 25% of cases and finally 4 patients died. Analyzing these cases predisposing factors and different therapeutic options of this condition are discussed. Treatment options of radiation induced enteritis are limited; however, targeted therapy significantly improves the outcome. Cooperation between oncologist, gastroenterologist and surgeon is required to establish adequate therapeutic plan.

[From project-based sample collection to biobank]. / Projektalapú mintagyujtéstol a biobankig.

The research group takes samples for molecular genetical examinations from tumors removed during operations within ischemic time interval. Samples are stored in liquid nitrogen. Clinical data of these patients are recorded in an informatics system developed by the group. Patients are followed in an out-patient clinic set up for this purpose not financed by the National Health Insurance Fund. Tissue samples and follow up data are used to cooperate with molecular genetical laboratories.

Inflammation of ectopic pancreatic tissue in a Meckel's diverticulum causing acute abdominal symptoms: a case report and review of the literature.

An unusual case of acute abdomen was caused by the inflammation of ectopic pancreatic tissue in a Meckel's diverticulum. A 49-year-old man presented with acute abdominal pain, and the clinical diagnosis of acute appendicitis was established. During laparotomy, a normal appendix of unusual localization near the gallbladder and a Meckel's diverticulum with an inflamed tip were found. Histological examination showed acute inflammation of heterotopic pancreatic tissue along with normal ectopic gastric and duodenal mucosa within the wall of the diverticulum. Fat necrosis was also ascertained. The authors believe that this is the first report of acute inflammation of ectopic pancreatic tissue and the presence of normal ectopic gastric and duodenal tissue in the same Meckel's diverticulum.

[Laparoscopic or open appendectomy?]. / Laparoszkópos vagy nyílt appendectomia?

UNLABELLED: Despite the fact that laparoscopic appendectomy was one of the first performed minimally invasive surgical procedures, the benefits and indications of its use are still controversial. METHODS: Data of patients with the diagnosis of appendicitis operated either with laparoscopic (LA) or open (OA) appendectomy were collected and analyzed. PATIENTS: This study involved 273 consecutive patients who had undergone appendectomy with the diagnosis of acute appendicitis at the Uzsoki Teaching Hospital, Department of Surgery between January 2005 and December 2007. 185 patients (68%) operated with the laparoscopic, 88 (32%) with the open technique, in the third year 89% of the cases underwent laparoscopic appendectomy. RESULTS: The conversion rate was 27%, the reason of the conversion was the progression of the disease in 35 patients (70%) and technical in 15 cases (30%). The wound infection rate was 8% in the LA and 18% in the OA group ( p = 0.022). No significant difference was found in the reoperation rate and in the hospital readmission rate between the two groups. There was one insufficiency which was treated with conservative therapy. The hospital stay was significantly lower in the laparoscopic group ( p = 0.031). CONCLUSIONS: This study demonstrated that laparoscopic appendectomy has significant advantages over open appendectomy. In our practice, laparoscopic appendectomy is the first choice of procedure in acute appendicitis.