Neoadjuvant chemoradiotherapy of rectal carcinoma : Baseline hematologic parameters influencing outcomes.

BACKGROUND: The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). RESULTS: Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00-1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01-1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00-1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01-1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00-1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02). CONCLUSION: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.

[Hopes and pitfalls of the molecular classification of breast cancer]. / Nadeje a úskalí molekulární klasifikace karcinomu prsu.

Traditional histopathological diagnosis of breast cancer has been extended in recent years through the results of additional methods. Today, the results of the detection of hormone receptors, HER-2/neu, and Ki67 antigen are thus an integral part of the histopathological diagnosis. A critical factor for the success of these tests is the fulfillment of pre-analytical phase conditions - i.e. optimal fixation, as well as taking into account the heterogeneous nature of the neoplastic population. In addition to the above-mentioned markers - which have become a routine practice in recent years, there are many efforts to include the molecular characteristics of tumors both in tumor classification as well as in the prediction of results of cancer treatment. Most of the work is based on the use of gene expression profiles. On the basis of the detection of increased or decreased expression of a large number of genes, it is possible to find a set of multiple genes correlating with the biological behavior of the tumor. Using this approach, four basic subgroups of breast cancer have been identified - luminal, basal-like, HER-2 enriched and normal gland-like. Over the course of time, the number of molecular categories has expanded - originally a homogenous group of luminal cancers has been subclassified into the luminal A, B and C. Also within basal-like carcinomas additional subgroups have been identified. However, the results of studies dealing with the analysis of gene expression profiles suggest that our understanding of the biology of breast cancer is far from being complete. The individual categories are defined differently in various publications and thus the comparison of the results of these studies is very difficult. Another approach for the molecular classification of breast cancer is the immunohistochemical detection of various proteins used as a surrogate marker instead of the detection of the mRNA of individual genes. The advantage of this approach is the possibility to use even archive material, as well as much lower costs. On the other hand, its main limitation is the inability of parallel detection of thousands of markers, unlike in genomic profiling. The results of molecular classification are, however, not fundamentally surprising. The fact that breast cancer tumor stem cells can differentiate towards myoepithelial (or basal) and luminal cells has been known for a long time. These two lines of differentiation are - among others - characterized by differential expression of cytoskeletal proteins as well as of other molecules. These findings have been confirmed by the results of molecular studies - either those based on gene expression profiling or immunohistochemical ones. Research results in gene expression profiling have relatively quickly translated into clinical practice. At present, several commercially available certified tests serve as a complementary source of information for decisions about clinical treatment.

Follicular variant of papillary carcinoma presenting as a hyperfunctioning thyroid nodule.

In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.

Tubuloglomerular Disease With Cone-Shaped Epiphyses Associated With Hypomorphic Variant and a Novel p.Cys14Arg in the TTC21B Gene: A Case Report.

Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with proteinuric diseases, such as nephrotic syndrome. Our patient manifested as an infant with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis (FSGS). Multiple phalangeal cone-shaped epiphyses of the hand were seen on X-ray. Next-generation sequencing revealed the well-described p.Pro209Leu heterozygous variant and a novel heterozygous p.Cys14Arg variant in the TTC21B gene. Our finding confirmed that the causative variants in the TTC21B gene may contribute to a spectrum of clinical features, such as glomerular proteinuric disease with tubulointerstitial involvement and skeletal abnormalities.

The Time Between Chemoradiation and Surgery for Rectal Carcinoma Negatively Influences Mesorectal Excision Quality.

Total mesorectal excision quality (TMEq) is a prognostic factor associated with local recurrence in rectal adenocarcinoma. Neoadjuvant chemoradiotherapy (NCRT) reduces the risk of tumor recurrence, but may compromise TMEq. The time between NCRT and surgery (TTS) and how it influences TMEq and tumor control were evaluated. In prospective registry, 236 patients after NCRT and TME were analyzed. NCRT involved radiotherapy with 45 Gy to the pelvis, plus tumor boost dose 5.4 Gy with concurrent 5-fluorouracil infusion. NCRT was followed by TME after 9 weeks on average (median 9.4 ± SD 2.5). TMEq was parametrically analyzed by standard three-grade system. With median follow-up of 47.5 months, 3-year overall survival (OS) was 83.8%, disease-free survival (DFS) was 77.7%, and 6.4% was the rate of local recurrence (LR). TTS was not associated with OS, DFS, or LR. TMEq was found to be associated with LR in univariate analysis, but not in multivariate, where pathological tumor stage and resection margins remained dominant predictors. TMEq was negatively influenced by inferior location of the tumor, longer TTS, higher tumor and nodal stage, presence of tumor perforation, perineural invasion, and close/positive resection margins. Nonetheless, TTS remained a strong predictor of TMEq in multivariate analyses. TTS was proven to be an independent predictor of TMEq. With longer TTS, fewer complete TME with intact mesorectal plane were observed. However, TTS was not associated with survival deterioration or tumor recurrence. These were negatively influenced by other factors interfering with TMEq, especially by pathological tumor stage and resection margins.

Saprochaete clavata Invasive Infections - A New Threat to Hematological-Oncological Patients.

BACKGROUND: Saprochaete clavata (formerly Geotrichum clavatum, now proposed as Magnusiomyces clavatus) is a filamentous yeast-like fungus that has recently been described as an emerging pathogen mostly in patients with acute leukemia. METHODS: This is a retrospective study of patients diagnosed with proven and probable S. clavata infection at the University Hospital, Hradec Králové, Czechia between March 2005 and December 2017. Previous cases were identified from the literature and FungiScope® database. RESULTS: Six new cases (5 females, 1 male) of blood-stream S. clavata infections at the hemato-oncological department were described including epidemiological data of additional 48 patients colonized with the species. Overall, 116 strains of S. clavata were isolated from different clinical specimens of 54 patients; most of them belonged to the respiratory tract (60.3%). S. clavata was the most frequent species among arthroconidial yeasts (Trichosporon, Galactomyces, Magnusiomyces) recovered from the blood. All our patients with S. clavata infection had profound neutropenia, a central venous catheter, broad-spectrum antibiotics and antifungal prophylaxis; four had a history of a biliary tract system disease. The diagnosis was based on a positive blood culture in all patients. Four patients died of multiorgan failure and sepsis despite treatment with lipid-based amphotericin B and/or voriconazole. From the literature and FungiScope database, 67 previous cases of S. clavata infections were evaluated in context of our cases. CONCLUSION: Saprochaete clavata infection represents a life-threatening mycosis in severely immunocompromised patients. The successful outcome of treatment seems to be critically dependent on the early diagnosis and the recovery of underlying conditions associated with immune dysfunction or deficiency.

Distribution of metastases in mesorectum is unpredictable: Metastases do not respect tumor localization even in small non-circumferential rectal cancers.

INTRODUCTION: Low anterior resection with total mesorectal excision (TME) is the gold standard for surgical treatment of rectal carcinoma. The radicality of this procedure is negatively counterbalanced by morbidity, lethality, and numerous other complications. Local excision would appear to be an attractive alternative, but its radicality is disputable due to risk of undetected metastasis to the mesorectum. The study aimed to determine the location of mesorectal metastases with respect to circumferentially - located tumors in patients with tumors involving less than one-third of the rectal circumference. MATERIALS AND METHODS: Resected specimens from patients with tumors smaller than one-third of the circumference were divided into: Sector A - tumorous, and Sector B - nontumorous. Group A was created by the pathologist cutting part of the rectal wall with the adjacent mesorectum, as though imitating a full-thickness excision. RESULTS: The study comprised 35 patients with a mean age of 66 years, of which 23 were men (65.7%) and 12 were women (34.2%). Tumors were predominantly (y)pT1-T2; a total of 799 lymph nodes and 5 tumor satellites were examined. Six patients (17.1%) were identified as stage (y)pN+. A total of 3 positive findings (lymph node metastasis or satellites) were detected in 3 patients (8.5%) in tumorous Sector A; and 8 positive findings were detected in 4 patients (11.4%) in non-tumorous Sector B. CONCLUSION: Rectal carcinoma involving one-third of the rectal circumference metastasizes discontinuously, and spreads into parts of the mesorectum beyond the tumor area.

Impact of Hashimoto's thyroiditis, TSH levels, and anti-thyroid antibody positivity on differentiated thyroid carcinoma incidence.

INTRODUCTION: The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear. MATERIAL AND METHODS: A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC. RESULTS: Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716-1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403-3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate. CONCLUSIONS: No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT.

Higher risk of incomplete mesorectal excision and positive circumferential margin in low rectal cancer regardless of surgical technique.

INTRODUCTION: Currently, the predominant question is whether a laparoscopic approach is comparatively radical in comparison with an open access approach, especially in the circumferential resection margin and quality of the completeness of total mesorectal excision. These factors are important in determining the quality of surgical care as well as long-term results of the treatment. AIM: This article focuses on the evaluation of circumferential resection margins and on the quality of mesorectal excision of middle and lower rectum tumors. In addition, laparoscopic and open techniques are compared. MATERIAL AND METHODS: Data were collected prospectively and stored in a rectal cancer registry over a 3-year period. The parameters studied were age, sex, body mass index, localization and topography of the tumor, clinical stage, neoadjuvant chemotherapy and its response, the type of surgery, character of the circumferential and distal margins, quality of the mesorectal excision, pT and pN. RESULTS: One hundred and twenty-five patients were chosen for our study. Laparoscopy was performed in 53 operations and a conventional approach was performed in 72 operations. Complete mesorectal excision was achieved in 54.7% of laparoscopic operations versus 44.4% in the conventional technique; partially complete excision was performed in 20.8 and 12.5%, respectively. Incomplete excisions were described in 24.5 and 43.1% (p = 0.085). Positive circumferential margin occurred during laparoscopic surgery in 11 (20.8%) patients, and in the case of conventional resection in 27 (37.5%) patients (p = 0.044). CONCLUSIONS: Our study showed comparable results between laparoscopic and open access procedures during rectal resection. The results achieved, in particular in the quality of the mesorectal excision and negative circumferential resection margin, show that the laparoscopic approach is comparable to conventional surgical techniques, with an adequate surgical outcome, in the treatment of rectal cancer.

Prognostic significance of human papillomavirus (HPV) status and expression of selected markers (HER2/neu, EGFR, VEGF, CD34, p63, p53 and Ki67/MIB-1) on outcome after (chemo-) radiotherapy in patients with squamous cell carcinoma of uterine cervix.

The aim of the retrospective study was to evaluate prognostic significance of human papillomavirus (HPV) status and expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2/neu), vascular endothelial growth factor (VEGF), CD34 antigen, tumor suppressors p63 and p53, and Ki67/MIB-1 in squamous cell carcinoma of the uterine cervix (SCCC) treated with radiotherapy or chemoradiotherapy. Seventy-two consecutive patients with SCCC, diagnosed and treated with (chemo-) radiotherapy with a curative intent at the University Hospital Hradec Kralove between August 1998 and August 2008, were enrolled in the study. The median follow-up period was 57 months (range 5-152). The tested biological factors were evaluated by polymerase chain reaction (HPV status) and by immunohistochemistry (remaining above mentioned markers) from archival paraffin embedded original diagnostic tumor samples. A statistical significant correlation was observed between low expression of p63 and poor overall survival (p = 0.001), although the complete response probability was influenced with borderline statistical significance (p = 0.05). However, the results could be affected by the statistical error due to the small number of p63 negative patients. HPV positivity and EGFR staining intensity was associated with higher complete response probability (p = 0.038 and p = 0.044, resp.). All other results were not significant. Neither HPV positivity nor EGFR staining intensity were reflected in the overall survival evaluation. In conclusion, the presented study did not confirm any apparently significant association of the suggested markers with prognosis of SCCC in patients treated with (chemo-) radiotherapy.