Surgical Treatment of Lithiasis of the Main Pancreatic Duct: A Challenging Case and a Literature Review.

Pancreaticolithiasis represents a rare phenomenon, being superimposed most of the time on a form of chronic pancreatitis of multifactorial etiology. Pancreaticolithiasis is a late complication of the phenomenon of chronic pancreatitis. The reverberant inflammatory process, followed by the fibrotic degeneration of the pancreatic parenchyma, and pancreatic fluid stasis at the ductal level are factors that contribute to the phenomenon of calcium precipitation. This article describes the case of a patient with a diagnosis of pancreaticolithiasis (Wirsung duct lithiasis), a phenomenon superimposed on chronic pancreatitis of ethanolic cause (Rosemont classification). It was decided to perform surgery via the classical approach with the perfection of corporeo-caudal pancreatectomy and preservation of the splenic vessels (Kimura procedure) with pancreatico-jejunal anastomosis on the Roux-en-Y loop. The aim of this study is to identify the best method of treatment for pancreaticolithiasis. To enhance the case and provide a basis for standardization, a literature review was carried out, which included a total of six articles. The results of this study highlight that, currently, the management of symptomatic pancreaticolithiasis encompasses medical therapy (enzyme replacement therapy), interventional therapy (ESWL (extracorporeal shock wave lithotripsy) ± ERCP (endoscopic retrograde cholangiopancreatography), ERCP + sphincterotomy + stent insertion, and POP (oral pancreatoscopy)), and surgical treatment. In conclusion, based on the analysis conducted in this study, the size of the calculi present determines which is the suitable therapeutic care. Unlike stones over 0.5 cm, when surgery is explicitly advised for therapeutic purposes in the absence of endoscopic techniques, stones under 0.5 cm should be treated using endoscopic procedures.

Primary Thyroid Lymphoma: A Retrospective-Observational Study in a Single Institutional Center.

Background and Objectives: primary thyroid lymphoma (PTL) is a rare neoplasm, displaying a variety of histological features. It is often a challenge for pathologists to diagnose this tumor. Materials and Methods: this study is a retrospective analysis of clinical and pathological characteristics of a group of eleven patients (eight women and three men, mean age 68 years, range 50-80 years) diagnosed with PTL. Results: nine patients (81.81%) presented a tumor with progressive growth in the anterior cervical region, usually painless and accompanied by local compressive signs. Histologically, we identified six cases (55%) of diffuse large B-cell lymphoma, three cases (27%) of extranodal marginal zone lymphoma, one case (9%) of follicular lymphoma, and one case (9%) of mixed follicular-diffuse lymphoma. PTL was associated with microscopic Hashimoto autoimmune thyroiditis in ten cases (90.9%). Ten patients (90.9%) presented with localized disease (stage I-IIE). A percentage of 60% of patients survived over 5 years. We observed an overall longer survival in patients under 70 years of age. Conclusions: PTL represents a diagnosis that needs to be taken into account, especially in women with a history of Hashimoto autoimmune thyroiditis, presenting a cervical tumor with progressive growth. PTL is a lymphoid neoplasia with favorable outcome, with relatively long survival if it is diagnosed at younger ages.

Colorectal Carcinomas: Searching for New Histological Parameters Associated with Lymph Node Metastases.

Background and Objectives: Colorectal cancer (CRC) continues to be an essential public health problem. Our study aimed to evaluate the prognostic significance of classic prognostic factors and some less-studied histopathological parameters in CRC. Materials and Methods: We performed a retrospective study on 71 colorectal carcinoma patients who underwent surgery at the "Pius Brînzeu" County Clinical Emergency Hospital in Timișoara, Romania. We analyzed the classic parameters but also tumor budding (TB), poorly differentiated clusters (PDCs) of cells, tumor-infiltrating lymphocytes (TILs), and the configuration of the tumor border on hematoxylin-eosin slides. Results: A high degree of malignancy (p = 0.006), deep invasion of the intestinal wall (p = 0.003), an advanced stage of the disease (p < 0.0001), lymphovascular invasion (p < 0.0001), perineural invasion (p < 0.0001), high-grade TB (p < 0.0001), high-grade PDCs (p < 0.0001), infiltrative tumor border configuration (p < 0.0001) showed a positive correlation with lymph node metastases. Conclusions: The analyzed parameters positively correlate with unfavorable prognostic factors in CRC. We highlight the value of classic prognostic factors along with a series of less-known parameters that are more accessible and easier to evaluate using standard staining techniques and that could predict the risk of relapse or aggressive evolution in patients with CRC.

A rare form of hyperthyroidism leading to the diagnosis of acromegaly: A case report.

Acromegaly is a rare disease, usually caused by a pituitary tumor. It typically exhibits slow evolution and can result in numerous complications. In the present case report, the patient presented with hyperthyroidism associated with ophthalmopathy and right nodular goiter. The laboratory tests revealed persistent high levels of phosphorus without an apparent cause. After ruling out common pathologies associated with this finding, a focus was placed on the clinical aspects associated with acromegaly, a rare cause of hyperphosphatemia. Laboratory tests and MRI confirmed the diagnosis. The patient underwent transsphenoidal surgery, but the disease remained active, thus medical treatment was initiated, to a poor initial response. Associated with acromegaly, two distinct thyroid pathologies were diagnosed: Toxic adenoma and Graves' disease. This case highlights the challenges in diagnosing and managing a rare endocrine pathology.

Invasive Cutaneous Melanoma: Evaluating the Prognostic Significance of Some Parameters Associated with Lymph Node Metastases.

Background and Objectives: This study aimed to assess the clinical-pathological profile of patients with invasive cutaneous melanomas and to identify the parameters with a prognostic role in the lymph nodal spread of this malignant tumor. Materials and Methods: We performed a retrospective study on patients with invasive cutaneous melanomas who underwent surgery in the "Pius Brînzeu" County Clinical Emergency Hospital from Timișoara, Romania, and were evaluated for the status of loco-regional lymph nodes. We selected and analyzed some parameters searching for their relationship with lymph node metastases. Results: We identified 79 patients with invasive cutaneous melanomas (29 men and 50 women, mean age 59.36 years). A percentage of 58.3% of melanomas had Breslow tumor thickness >2 mm; 69.6% of melanomas showed a Clark level IV-V. Tumor ulceration was present in 59.5% of melanomas. A mitotic rate of ≥5 mitoses/mm2 was observed in 48.1% of melanomas. Tumor-infiltrating lymphocytes (TILs), non-brisk, were present in 59.5% of cases and 22.8% of patients had satellite/in-transit metastasis (SINTM). Tumor regression was identified in 44.3% of cases. Lymph nodes metastases were found in 43.1% of patients. Statistical analysis showed that lymph node metastases were more frequent in melanomas with Breslow thickness >2 mm (p = 0.0002), high Clark level (p = 0.0026), mitotic rate >5 mitoses/mm2 (p = 0.0044), ulceration (p = 0.0107), lymphovascular invasion (p = 0.0182), SINTM (p = 0.0302), and non-brisk TILs (p = 0.0302). Conclusions: The Breslow thickness >2 mm, high Clark level, high mitotic rate and ulceration are the most important prognostic factors for lymph nodal spread in cutaneous melanomas. However, some melanomas without these clinical-pathological features can have an unexpected, aggressive evolution, which entails the necessity of close and prolonged clinical follow-up of patients, including those with lesions considered without risk.

The impact of the COVID-19 pandemic on thyroid nodular disease: a retrospective study in a single center in the western part of Romania.

Introduction: The COVID-19 pandemic had a significant impact on the healthcare system, leading to a prioritization of hospital admissions in many countries. Romania was no exception, and it had to restrict patient access to medical services in hospitals with chronic diseases and oncological pathology, including thyroid cancer. This study aimed to compare the clinical and pathological factors of patients with nodular thyroid disease diagnosed and surgically treated during the two years before and after the COVID-19 pandemic, in a single medical institution. Methods: The retrospective study included 1505 patients who were diagnosed and operated on for nodular thyroid disease between January 2018 and December 2021. The patients were divided into two groups: the "PRECOVID" group (January 2018 to February 2020), and the "POSTCOVID" group (March 2020 to December 2021). The analyzed parameters included patients' gender, age, preoperative diagnosis, type of surgical intervention, and pathological diagnosis. Results: A significant decrease was observed in the number of surgeries performed for thyroid nodular disease during the COVID-19 pandemic period (450 versus 1055 cases, p<0.00001). There was a significant decrease in the number of surgical reinterventions (0.9% in the POSTCOVID group versus 2.9% in the PRECOVID group, p=0.01) and a significant increase in the number of total thyroidectomies (84.9% in the POSTCOVID group versus 80.1% in the PRECOVID group, p=0.02). We also observed a higher incidence of malignant/borderline tumors in the POSTCOVID group compared to the PRECOVID group (p=0.04) and a significantly higher frequency of aggressive forms of thyroid cancer in the POSTCOVID group (p=0.0006). Discussion: The COVID-19 pandemic had a significant impact on the surgical management of nodular thyroid disease, resulting in a decrease in surgeries and a change in the type of surgical interventions performed. The higher incidence of malignant/borderline tumors diagnosed during the pandemic highlights the importance of timely diagnosis and treatment of thyroid nodules to prevent cancer progression.

Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas.

The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently,  we evaluated  associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t)  most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005) and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.

Three-Dimensional Virtual Pathology Specimens: Decrease in Student Performance upon Switching to Digital Models.

Several alternatives to formalin-stored physical specimens have been described in medical literature, but only a few studies have addressed the issue of learning outcomes when these materials were employed. The aim of this study was to conduct a prospective controlled study to assess student performance in learning anatomic pathology when adding three-dimensional (3D) virtual models as adjunct teaching materials in the study of macroscopic lesions. Third-year medical students (n = 501) enrolled at the Victor Babes University of Medicine and Pharmacy in Timisoara, Romania, were recruited to participate. Student performance was assessed through questionnaires. Students performed worse with new method, with poorer results in terms of overall (mean 77.6% ±SD 11.8% vs. 83.6% ±10.5) and individual question scores (percentage of questions with maximum score 34.6% ±25.6 vs. 47.7 ± 24.6). This decreased performance was generalizable, as it was observed across all language divisions and was independent of the teaching assistant involved in the process. In an open-ended feedback evaluation of the new 3D specimens, most students agreed that the new method was better, bringing arguments both for and against these models. Although subjectively the students found the novel teaching materials to be more helpful, their learning performance decreased. A wider implementation as well as exposure to the technique and use of virtual specimens in medical teaching could improve the students' performance outcome by accommodating the needs for novel teaching materials for digital natives.

Immunohistochemical expression of chemokine receptor in neuroendocrine neoplasms (CXCR4) of the gastrointestinal tract: a retrospective study of 71 cases.

AIM: C-X-C motif chemokine receptor 4 (CXCR4) is expressed in many tumor entities, including gastrointestinal neuroendocrine neoplasms (GI-NENs). However, the role of CXCR4 expression in GI-NENs has been less studied. Our objective was to investigate the expression of CXCR4 in a series of GI-NENs with various clinical and pathological features. METHODS: The immunohistochemical (IHC) expression of CXCR4 (clone UMB2) was examined in 71 GI-NENs and a semiquantitative immunoreactivity score (IRS) was calculated taking into consideration the intensity of the IHC reaction and the percentage of the tumor cells which showed positive expression. Results were compared with several clinical and pathological prognostic factors. RESULTS: High CXCR4 expression was noted in 31 (43.7%) cases. Low IRS values were more frequent in NENs from the small intestine (66.7%) and stomach (60%). Also, all appendix tumors had IRS value of zero. High CXCR4 expression was noticed in 52.5% of liver metastases, compared to 40.4% primary tumors. A significant relationship was observed between the CXCR4 expression and the tumor grade (p=0.0216), and high IRS value was correlated with clinical stages III and IV (p=0.0142) and lympho-vascular invasion (p=0.0129). 74.1% of G1 neuroendocrine tumors (NETs) had a low IRS, G3 NETs showed minor differences between low (42.9%) and high (57.1%) expression and 66.7% of neuroendocrine carcinomas (NECs) presented high expression of CXCR4. CONCLUSIONS: The present study highlighted that high CXCR4 expression is associated with high grade and advanced stage GI-NENs, as well as with metastatic cases. In these cases, high CXCR4 expression could serve as an important target for CXCR4 antagonists.

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5.

The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P=0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.

Presurgical Stratification of Thyroid Nodules - Is it really Needed? Current Guidelines versus Real Life.

Background: Thyroid surgery has various benign and malignant indications. A complete pre-surgical evaluation guides the selection of cases and determines the appropriate extent of the intervention. Minimizing the number of unneeded thyroidectomies could reduce hospitalization costs, as well as post-surgery complications and iatrogenic hypothyroidism. The aim of this study was to retrospectively evaluate the presenting reasons of patients admitted to the hospital for thyroid surgeries and to estimate the need of total thyroidectomies. Methodology: The study included patients admitted in all three Surgical Departments in Timisoara Emergency County Hospital, between January 1st 2018 and December 31st 2019 (2 years). Results: A number of 1036 thyroid surgeries had been performed in 1027 patients and were retrospectively analyzed, comparing the pre-surgical diagnosis with the pathology report. Suspicion of malignancy, compression or functional autonomy was described in 326 /824 total thyroidectomy cases. Cancer was detected in 338 out of the 1027 patients (32.92%), including 39 borderline lesions. A proportion of 80.7% were papillary thyroid cancers. The current presurgical evaluation generated a number of 475 cases displaying differences between the presurgical and postsurgical diagnostic. The phenomenon was observed both in total thyroidectomy and in lobectomy interventions: 22.8% of the lobectomies were diagnosed with thyroid cancer. Conclusion: Our findings confirm that a reliable multidisciplinary approach with standardized presurgical clinical, biochemical and ultrasound evaluation is crucial in patients with indication for thyroid surgery, in order to avoid unnecessary surgeries.

Effects of mine waste water on rat: bioaccumulation and histopathological evaluation.

The highlighting of the bioaccumulation capacity of metals in the internal organs, the mode of distribution at the level of internal organs, the interactions between them, respectively, and the histological changes occurred at the level of the liver and kidneys are the main aspects addressed in the present study. The experiment was performed on 4 groups of Wistar rats: 3 groups which were administered water from rivers located in the vicinity of the Bor mining operation and 1 control group. The determination of the metal content in the administered water samples and in the internal organs was performed using the flame atomic absorption spectrophotometer. Tissue alterations were assessed by histological technique and hematoxylin-eosin staining. The metal retention capacity in the internal organs differs depending on the metal concentration in the administered water sample but also on the organ in which the determination was made. Also, correlations were established between the concentrations of metals at the level of the organs, showing (a) positive and significant correlations-at the level of the heart between Zn and Cu, Fe, and Mn and at the level of the lungs between Mn and Cd-but the most numerous were reported in the testicle; (b) moderate correlations at liver level between Fe and Zn, at spleen level between Cu and Mn and Cd and at the level of the kidneys between Pb and Zn, Cu, and Fe; (c) negative correlations at renal level between Pb and Mn; and (d) insignificant correlations between Pb and Fe. The histological changes identified at the level of the liver and kidney become more obvious, and their aggravation is registered with the increase of the metal content.

Collision tumor of the thyroid - a challenge during the COVID-19 pandemic.

Some of the patients with anaplastic thyroid carcinomas have a coexistent differentiated thyroid cancer, sustaining the hypothesis that this cancer may develop from more differentiated tumors. We describe a case with a collision tumor of the thyroid, defined as a neoplastic lesion composed of two distinct cell populations, with distinct borders. The patient presented during the COVID-19 pandemic with dysphonia, dyspnea, multinodular goiter and a painless, rapidly enlarging, left cervical swelling. She had been first time diagnosed with left nodular goiter in 2007, with an indication for surgery, which she declined. After partial excision of the left latero-cervical adenopathy, the pathological analysis showed massive lymph node metastasis from anaplastic thyroid cancer. A total thyroidectomy was done; the postoperative pathological exam identified a papillary thyroid microcarcinoma in the right lobe and an anaplastic thyroid cancer in the left lobe. Postoperatively, levothyroxine treatment was started and the patient was referred to radiotherapy. This case highlights the importance of urgent management of some cases with compressive multinodular goiter, even during the COVID-19 pandemic.

The Impact of Artificial Intelligence in the Endoscopic Assessment of Premalignant and Malignant Esophageal Lesions: Present and Future.

In the gastroenterology field, the impact of artificial intelligence was investigated for the purposes of diagnostics, risk stratification of patients, improvement in quality of endoscopic procedures and early detection of neoplastic diseases, implementation of the best treatment strategy, and optimization of patient prognosis. Computer-assisted diagnostic systems to evaluate upper endoscopy images have recently emerged as a supporting tool in endoscopy due to the risks of misdiagnosis related to standard endoscopy and different expertise levels of endoscopists, time-consuming procedures, lack of availability of advanced procedures, increasing workloads, and development of endoscopic mass screening programs. Recent research has tended toward computerized, automatic, and real-time detection of lesions, which are approaches that offer utility in daily practice. Despite promising results, certain studies might overexaggerate the diagnostic accuracy of artificial systems, and several limitations remain to be overcome in the future. Therefore, additional multicenter randomized trials and the development of existent database platforms are needed to certify clinical implementation. This paper presents an overview of the literature and the current knowledge of the usefulness of different types of machine learning systems in the assessment of premalignant and malignant esophageal lesions via conventional and advanced endoscopic procedures. This study makes a presentation of the artificial intelligence terminology and refers also to the most prominent recent research on computer-assisted diagnosis of neoplasia on Barrett's esophagus and early esophageal squamous cell carcinoma, and prediction of invasion depth in esophageal neoplasms. Furthermore, this review highlights the main directions of future doctor-computer collaborations in which machines are expected to improve the quality of medical action and routine clinical workflow, thus reducing the burden on physicians.

Clinical relevance and accuracy of p63 and TTF-1 for better approach of small cell lung carcinoma versus poorly differentiated nonkeratinizing squamous cell carcinoma.

Lung cancer high mortality rate remains a major problem, despite the actual progress in its early detection and therapeutic design. Since lung cancer' treatment requires separation of tumors in small cell carcinoma and non-small cell carcinoma, the histopathological diagnosis focuses on this basic distinction, while immunohistochemistry contributes considerably to confirm the diagnosis accuracy. In order to check the assumption that p63 is a useful marker for squamous cellular differentiation, we used two antibodies: anti-p63 and anti-thyroid transcription factor-1 (TTF-1), based on their immunoexpression to differentiate small cell lung carcinoma (SCLC) from poorly differentiated nonkeratinizing squamous cell carcinoma (SCC). Our study included 48 cases of lung carcinoma (lung biopsies and wedge resection formalin-fixed and paraffin-embedded). The 48 cases included 23 SCLCs and 25 poorly differentiated nonkeratinizing SCC. The expressions of p63 and TTF-1, respectively, proved to be useful in distinguishing SCLC from poorly differentiated nonkeratinizing SCC, on surgical and biopsic sections. The p63 positivity and TTF-1 negative expression consequently indicated a poorly differentiated nonkeratinizing SCC, while the opposite immunostaining pattern was flagged in SCLC. Our results are useful for a targeted therapy, as long as they point out a significant role in marking of the correct diagnosis of lung tumors.

Malignant hepatic vascular tumors in adults: Characteristics, diagnostic difficulties and current management.

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation (LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma (HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation Association-European Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma (HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient. Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches, alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.

Poorly differentiated clusters: prognostic significance in colorectal carcinomas immunohistochemistry images.

Colorectal cancer (CRC) remains a major public health burden worldwide, despite increased knowledge on its pathogenesis and advances in therapy. We aimed to evaluate a new histological grading system based on poorly differentiated clusters (PDCs) counting - the PDCs grade (PDCs-G), and its clinicopathological and prognostic significance, compared to the World Health Organisation (WHO) grading system (WHO grade). We reviewed 71 surgical resection specimens for CRC from the Emergency County Hospital "Pius Brînzeu" Timisoara. The cases were graded using the WHO grade and the PDCs-G, with further analysis of their association with the other recognised prognostic parameters. Using the WHO grade, 9% of the analysed cases were G1, 80% G2, 11% G3, and none of the tumours was graded G4, while in the PDCs-G 16% were G1, 45% G2, and 39% G3. In multivariate analysis PDCs-G was significantly associated with the American Joint Committee on Cancer stage of the disease (AJCC stage) (p = 0.0003), depth of invasion (pT) (p = 0.0084), nodal status (LNM) (p < 0.0001), lymphovascular invasion (LVI) (p < 0.0001), perineural invasion (PNI) (p < 0.0052), and tumour border configuration (p < 0.0001). The novel grading system based on PDCs counting is an additional histological tool in the evaluation of CRC and a promising new prognostic factor for these patients.

Prognostic significance of E-cadherin expression in hepatocellular carcinoma: correlations with clinical features.

BACKGROUND: Hepatocellular carcinoma (HCC) represents a major public health issue, being associated with high morbidity and mortality rates. Previous studies have demonstrated that reduction and∕or absence of E-cadherin expression is correlated with a potential for invasion and low survival rate in patients with HCC. PATIENTS, MATERIALS AND METHODS: We assessed the immunohistochemical expression of E-cadherin in 32 HCCs and peritumoral hepatic tissues using monoclonal anti-E-cadherin antibody (clone EP700Y), at 1:50 dilution, followed by incubation with Labeled Streptavidin-Biotin 2 (LSAB2) for 20 minutes, visualization of the reaction with 3,3'-Diaminobenzidine (DAB) and counterstaining with Mayer's Hematoxylin. RESULTS: The results we obtained show: an aberrant E-cadherin expression more frequent in dysplastic nodules (p=0.285) and in 81.25% of HCC cases, as compared to normal hepatic tissue (p<0.001); the absence of a statistically significant relationship between E-cadherin expression and patients' gender (p=0.854), tumor localization (p=0.429), associated viral infection [hepatitis B virus (HBV) or hepatitis C virus (HCV)] (p=0.513) or tumor size (p=0.788); the rate of positive E-cadherin expression was significantly higher in tumors with capsular infiltration (75%) (p=0.017) and does not appear to be influenced by vascular invasion (62.5%) (p=0.411), the presence of satellite nodules (p=0.285) or the serum level of alpha-fetoprotein (α-FP) (p=0.787). CONCLUSIONS: Reduced E-cadherin expression indicates a poor prognosis for patients with HCC and can be considered a potential predictive marker for the prognosis of these patients.

Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer.

Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with different clinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.

2D-Shear Wave Elastography in the Evaluation of Parathyroid Lesions in Patients with Hyperparathyroidism.

BACKGROUND AND AIMS: 2D-shear wave elastography (2D-SWE) is a relatively new elastographic technique. The aim of the present study is to determine the values of the elasticity indexes (EI) measured by 2D-SWE in parathyroid benign lesions (adenomas or hyperplasia) and to establish if this investigation is helpful for the preoperative identification of the parathyroid adenoma. MATERIAL AND METHODS: The study groups were represented by 22 patients with primary or tertiary hyperparathyroidism, diagnosed by specific tests, and 43 healthy controls, in whom the thyroid parenchyma was evaluated, in order to compare the EI of the thyroid tissue with those of the parathyroid lesions. RESULTS: The mean EI measured by 2D-SWE in the parathyroid lesions was 10.2 ± 4.9 kPa, significantly lower than that of the normal thyroid parenchyma (19.5 ± 7.6 kPa; p = 0.007), indicating soft tissue. For a cutoff value of 12.5 kPa, the EI assessed by 2D-SWE had a sensitivity of 93% and a specificity of 86% (AUC = 0.949; p < 0.001) for predicting parathyroid lesions. CONCLUSION: A value lower than 12.5 kPa for the mean EI measured by 2D-SWE can be used to confirm that the lesion/nodule is a parathyroid adenoma.