Intratumor heterogeneity in colorectal cancer: Distribution of tumor suppressor gene variants with regard to patient lymph node status.

Intratumor heterogeneity (ITH) results from accumulation of somatic mutations in the fractions of successive cancer cell generations. We aimed to use deep sequencing to investigate ITH in colorectal tumors with particular emphasis on variants in oncogenes (ONC) and tumor suppressor genes (TSG). Samples were collected from 16 patients with colorectal cancer and negative or positive lymph node status (n = 8 each). We deep-sequenced a panel of 56 cancer-related genes in the central and peripheral locations of T3 size primary tumors and healthy mucosa. The central region of T3 tumors has a different frequency profile and composition of genetic variants. This mutation profile is capable of independently discriminating patients with different lymph node status (p = 0.028) in the central region. We noted an increasing number of mutations outside of the central region of the tumor and a higher number of mutations in tumors from node-positive patients. Unexpectedly, in the healthy mucosa, we identified somatic mutations with variant allele frequencies, characteristic not only of heterozygotes and homozygotes but also of other discrete peaks (e.g., around 10%, 20%), suggestive of clonal expansion of certain mutant alleles. We found differences in the distribution of variant allele frequencies in TSGs when comparing node-negative and node-positive tumors (p = 0.029), as well as central and peripheral regions (p = 0.00399). TSGs may play an important role in the escape of the tumor toward metastatic colonization.

[Risk factors of malignancy in patients with fine needle aspiration biopsy results interpreted as "suspicious for follicular neoplasm"].

OBJECTIVE: Introduction: Approximately 10% of fine needle aspiration biopsy (FNAB) of thyroid nodules may be verified as "suspicious for follicular neoplasm"; this category involves follicular adenoma, follicular carcinoma, follicular variants of papillary carcinoma and subclass "suspicious for Hurthle cell neoplasm". At present, there is no diagnostic tool to discriminate between follicular adenoma and cancer. Most patients are required surgery to exclude malignant process. The aim: To define factors correlating with risk of malignancy in patients with FNAB of thyroid focal lesions and nodules verified as Bethesda tier IV. PATIENTS AND METHODS: Materials and Methods: In this study 110 consecutive patients were included. All patients were operated because of FNAB result "suspicious for follicular neoplasm" of thyroid gland at a single institution from January 2016 until March 2020. From this set, six specific categories were defined and the clinical records for patients were collected: sex, age, presence of oxyphilic cells, diameter of the tumour, presence of Hashimoto disease, aggregate amount of clinical and ultrasonographic features of malignancy according to ATA. RESULTS: Results: In 18 patients (16,3%) thyroid cancer occurred. Most frequent subtype turned out to be papillary cancer (66,6%). In group of benign lesion (92 patients) predominance of follicular adenoma was disclosed - (49%). Age, gender, tumour diameter, aggregate amount of clinical and ultrasonografic factors, presence of Hashimoto disease and fine needle aspiration biopsy result suspicious for Hurthle cell neoplasm did not correspond to increased risk of malignancy. CONCLUSION: Conclusions: In patients with FNAB results classified as Bethesda tier IV there are no reliable clinical features associated with low risk of malignancy and surgery should be consider in every case as most appropriate manner to exclude thyroid cancer .

[The impact of elective central lymph node dissection on postoperative pathological staging and surgical complication rate in patients with results of fine needle spiration biopsy suspicious for follicular neoplasm of thyroid].

OBJECTIVE: Introduction: Follicular-patterned lesions of the thyroid are common; these include follicular adenoma, follicular cancer and follicular variant of papillary cancer. At present, preoperative discrimination between follicular adenoma and follicular cancer is infeasible and most patients require surgery to confirm diagnosis. The aim: To assess the impact of elective central lymph node dissection on postoperative pathological staging and early surgical complication rate in patients operated for suspicion for follicular neoplasm or suspicion for oxyphilic neoplasm of thyroid. PATIENTS AND METHODS: Materials and Methods: Eighty consecutive patients operated between 2016-2018 in Third Department of General Surgery UJCM because of suspicious for follicular neoplasm of the thyroid were included into the study. Inclusion criteria were: the result of fine needle aspiration biopsy " suspicious for follicular/oxyphilic neoplasm", absence of invasive neoplasm features as follows infiltration of surrounding tissue or lymph nodes/distant metastases, informed consent. In all patients elective central lymph node dissection was performed. Surgical early postoperative complications were reported and the rate was compared between the study group and the control group consisting of patients operated on in the same period for benign nodular goitre. RESULTS: Results: In 10 (12,5%) patients thyroid cancer was diagnosed, including 8 (80%) patients with papillary cancer and 2 (20%) patients with follicular cancer. The most common benign lesion was follicular adenoma diagnosed in 42 (60%) patients. There were 129 lymph nodes dissected (mean 1.6 lymph node per 1 patient), all lymph nodes were clear of cancer cells. In 26 patients there were no lymph nodes in postoperative preparation. Metastatic lymph nodes were not identified in any patients of the study group with final diagnosis of thyroid cancer. No significant differences were identified in prevalence of early postoperative complications among the study group and the control group patients: unilateral recurrent laryngeal nerve (RLN) palsy 3.4% vs. 1.49%; p= 0,08), hypocalcemia (5% vs. 5.4%; p=0.86), postoperative hemorrhage (1.25% vs. 0.44; p=0.29). CONCLUSION: Conclusions: Elective central lymph node dissection at experienced surgical hands does not improve postoperative pathological staging and is not associated with higher risk of early postoperative complications.

[Giant supernumerary parathyroid adenoma as a cause of persistent primary hyperparathyroidism in a patient with a multiglandular parathyroid disease].

Despite the significant progress that has been made in recent years in parathyroid imaging, improvements in surgical techniques and availability of surgical quality control based on intraoperative parathyroid hormone levels (PTH) assay, approximately 1-5% of patients undergoing surgery have state of persistent hyperparathyroidism. The most common causes of persistent hyperparathyroidism are: limited surgical experience, a failure to recognize multiglandular parathyroid disease, ectopic parathyroid adenoma location, insufficient range of resection of diseased parathyroid glands, parathyroid capsule tearing leading to parathyromathosis, as well as parathyroid cancer. In this clinical observation the case of a 52-years old man is described who underwent surgical removal of 2 parathyroid adenomas, and within few days he was found to have persistent hypercalcemia. After completing the diagnostic imaging and biochemical work-up that patient underwent bilateral neck re-exploration with removal of ectopic giant supernumerary parathyroid adenoma (60 mm in diameter and 22.8 g in weight) which was localized in the upper part of the posterior mediastinum, resulting in stable normocalcemia afterwards.

[Haemorrhage after thyroid surgery]. / Krwotok po operacji tarczycy.

INTRODUCTION: Haemorrhage after thyroid surgery is rare, but if it occurs it is a life-threatening condition necessitating emergency surgery. The aim of this study was to evaluate prevalence and risk factors of haemorrhage after thyroid surgery. METHODS: A retrospective analysis was undertaken in a group of 8931 consecutive patients with various thyroid diseases treated in 2004-2013 at our institution. Potential risk factors for postoperative haemorrhage after thyroid surgery were analysed using logistic regression model. RESULTS: Haemorrhage after thyroid operation necessitating emergency surgery occurred in 40 (0.45%) of 8931 patients. None of the patients died within the perioperative period. Bleeding occurred within first 24 hours following surgery in 38 (95%) patients, and in the remaining 2 (5%) patients in more than 24 hours after initial surgery. The following risk factors for bleeding after thyroid operation were identified: male sex (OR 3.618; 1.762-7.430; p < 0.001), older age > or = 70 years (OR 3.052; 1.275-7.304; p = 0.012), surgery for hyperthyroidism (OR 2.873; 1.511-5.462; p = 0.001), smoking (OR 2.855; 1.502-5.428; p = 0.001), subtotal thyroidectomy in contrast to total thyroidectomy or lobectomy (OR 2.853; 1.356-6.004; p=0.006), and thyroid operation undertaken by resident in training in general surgery (OR 2.596; 1.393-4.837; p = 0.003). CONCLUSIONS: Haemorrhage after thyroid operation necessitating emergency surgical intervention occurs most frequently within first 24 hour following surgery. Hence, for safety reasons a minimum of 24-hour hospital stay is recommended in all patients with risk factors for postoperative bleeding after thyroid operation. Quality monitoring of thyroid surgery should include also risk factors for postoperative bleeding.

Expression of micro-ribonucleic acids in thyroid nodules and serum to discriminate between follicular adenoma and cancer in patients with a fine needle aspiration biopsy classified as suspicious for follicular neoplasm: A preliminary study.

BACKGROUND: Approximately 10% of thyroid nodules undergoing fine needle aspiration biopsy (FNAB) receive a suspicious for follicular neoplasm (SFN) classification. Currently, there is no diagnostic tool to preoperatively discriminate between follicular adenoma (FA) and thyroid cancer (TC), and most patients require surgery to exclude malignancy. OBJECTIVES: To characterize the micro-ribonucleic acid (miRNA) signature of tumors assessed as SFN and define circulating miRNA patterns to distinguish FA from follicular cancer in patients with thyroid nodules biopsied using FNAB. MATERIAL AND METHODS: The study included excised tumor and thyroid tissue samples from 80 consecutive patients collected by a pathologist in the operating theater. The miRNA was isolated from specimens at the Center for Medical Genomics OMICRON, and next-generation sequencing (NGS) was used to obtain target miRNAs. In addition, miRNA expression was detected in serum using polymerase chain reaction (PCR). RESULTS: Well-differentiated thyroid cancer (WDTC) samples had significantly higher expression levels of hsa-miR-146b-5p (p = 0.030) and hsa-miR-146b-3p (p = 0.032), while the expression levels of hsa-miR-195-3p were significantly lower (p = 0.032) in WDTC samples compared to FA specimens. The serum of TC patients showed markedly higher expression of the unique miRNA hsa-miR-195-3p (p = 0.039). CONCLUSIONS: The overexpression of hsa-miR-146b-5p and hsa-miR-146b-3p, and the downregulation of hsa-miR-195-3p expression could be used as biomarkers to distinguish FA from WDTC in patients with FNAB results classified as Bethesda tier IV. In addition, hsa-miR-195-3p could act as a serum biomarker for differentiating patients with FA from those with WDTC, and preoperative measurement of its expression would help avoid unnecessary surgeries. However, this concept needs further verification in a more substantial prospective study.

Intraoperative neuromonitoring of hypogastric plexus branches during surgery for rectal cancer - preliminary report.

AIM: The aim of this study was to present our preliminary experience with intraoperative neuromonitoring during rectal resection. MATERIALS AND METHODS: We qualified 4 patients (2 women, 2 men; age 42 - 53 years) with rectal cancer for surgery with intraoperative neuromonitoring. In all patients, functional tests of the anorectal area were performed before surgery. Action potentials from the sphincter complex in response to nerve fiber stimulation were recorded with electrodes implanted before surgery. Moreover, we inserted a standard, 18FR Foley's urinary catheter to which a T-tube was connected to allow urine outflow and measurement of pressure changes in the bladder induced by detrusor contractions during stimulation. RESULTS: Setting up neuromonitoring prolonged surgery time by 30 to 40 minutes, or even by 60 to 80 minutes in the case of the first two patients. Neuromonitoring itself took additional 20 to 30 minutes during surgery. In all patients, we stimulated branches of the inferior hypogastric plexus in their anatomical position during dissection. In three patients, we evoked responses both from the bladder and the sphincter in all planes of stimulation. In one patient, there was no response from the left side of the bladder, and in the same patient, we observed symptoms of neurogenic bladder. CONCLUSIONS: Based on the available literature and our own experience, we state that monitoring of bladder pressure and electromyographic signals from rectal sphincters enables visualization and preservation of autonomic nervous system structures, both sympathetic and parasympathetic. Intraoperative signals seem to be correlated with clinical presentation and functional examinations after surgery. In order to objectify our results, it is necessary to perform functional examinations before and after surgery in a larger group of patients.

Polymorphism rs7023923 and monocyte count in blood donors and coronary artery disease patients.

BACKGROUND: The importance of the role of monocytes in coronary artery disease (CAD) is well documented. An increased number of circulating monocytes is associated with higher incidence of CAD. Both environmental and genetic factors influence monocytosis. The latter have been extensively studied since the development of high-throughput genome-wide association studies. Several associations between polymorphisms and monocytosis were found among healthy individuals; the first example was rs7023923. The magnitude of the association of studied polymorphisms with the trait of interest is often confounded by environmental factors and may therefore differ between patient and healthy populations. It is very important to determine the magnitude of the association among patients to predict outcome of the disease, e.g. myocardial infarction. AIM: To determine whether the magnitude of association of rs7023923 with monocytosis, previously reported among healthy volunteers, is similar in patients in whom diagnosis of CAD was determined during elective coronarography. METHODS AND RESULTS: Leucocytosis and neutrophilocytosis were higher among patients with CAD, while thrombocytosis was lower. Monocyte count did not differ among the studied groups (p = 0.25). We confirmed the association of rs7023923 with monocytosis among healthy blood donors (p = 0.0156) but not among patients admitted for elective coronarography (p = 0.61). Inclusion of the age and sex of patients in the statistical model did not modify the results. CONCLUSIONS: Our data suggest that translation of the results of genetic association with the studied traits from healthy to patient population should be implemented with caution. It is possible that numerous environmental factors, which discriminate healthy volunteers from CAD patients, confound the magnitude of genetic associations and make interpretation of the data in patients less clear.