Storosios žarnos navikas, kuriam būdingas dominuojantis neuroendokrininis imunofenotipas: kur baigiasi adenokarcinoma?

MiNEN (mixed neuroendocrine-non-neuroendocrine neoplasm) is described in the 5th edition WHO classification of tumors of the digestive system as a mixed neoplasm, composed of neuroendocrine and non-neuroendocrine parts, each accounting for at least 30% of the tumor. Recently this formal criterion has been criticized based on the theory that both of these components could have a monoclonal origin and non-neuroendocrine cells develop neuroendocrinicity in the later evolutionary steps of adenocarcinoma. For this reason, the identification of pure adenocarcinoma component, that was overgrown by a more aggressive clone with neuroendocrine features, in a pathological specimen can be difficult and, in some cases, even impossible. So, it is likely that at least some of large cell neuroendocrine carcinomas follow the same pathway, a theory that is further supported by adenocarcinoma-like molecular alterations in these tumors. Precise diagnosis (which means identifying and naming each tumor component regardless of its size) is essential for a personalized treatment strategy. We present an illustrative case of a rectal neoplasm that could be classified as a poorly differentiated neuroendocrine carcinoma, but exhibits morphological heterogeneity, mucin production and has a typical KRAS mutation pointing to adenocarcinomatous origin, which makes MiNEN a more accurate diagnosis. The article discusses the key points in classification, pathogenesis, and diagnostic approach to help effectively manage such neoplasms.Remiantis penktojo leidimo 2019 m. Pasaulio sveikatos organizacijos klasifikatoriumi, MiNEN (mišrūs neuroendokrininiai ir neneuroendokrininiai navikai) apibūdinami kaip mišrios neoplazijos, sudarytos iš neuroendokrininio ir neneuroendokrininio komponentų, kurių kiekvienas sudaro ne mažiau kaip 30 proc. naviko. Šis kriterijus kritikuojamas, atsižvelgiant į adenokarcinomų ir neuroendokrininių storosios žarnos navikų bendros kilmės teoriją: teigiama, kad adenokarcinomos evoliucijos eigoje, kaupiantis molekulinėms ir genetinėms pažaidoms, neneuroendokrininės ląstelės įgavo neuroendokrininį fenotipą, todėl egzistuojantis adenokarcinomos komponentas gali būti sunkiai nustatomas arba visiškai neidentifikuojamas patologijos tyrimo metu. Tikėtina, kad bent dalis didelių ląstelių neuroendokrininių karcinomų taip pat yra šio onkogenezės kelio rezultatas; tai suponuoja adenokarcinomoms artimas minėtų navikų molekulinis profilis. Taigi tikslinga identifikuoti ir įvardyti visus kombinuotą naviką sudarančius komponentus, nepaisant šių komponentų dydžio, nes jie gali būti reikšmingi parenkant individualią gydymo strategiją. Minėtam principui iliustruoti straipsnyje pristatomas kolorektalinio naviko atvejis: navikas formaliai turėtų būti kategorizuotas kaip blogai diferencijuota neuroendokrininė karcinoma, tačiau dėl savo histologinio heterogeniškumo, identifikuojamos minimalios mucinų produkcijos ir KRAS mutacijos jis artimesnis MiNEN. Straipsnyje aptariami MiNEN klasifikacijos, patogenezės ir diagnostikos klausimai bei jų reikšmė gydymui ir prognozei

Pancreatic Mucinous Cystic Neoplasm with Associated Invasive Carcinoma: A Case Report and Literature Review

Background. Pancreatic mucinous cystic neoplasm (PMCN) with associated invasive carcinoma is a rare entity. According to the World Health Organisation (WHO) 2010, PMCN with associated invasive carcinoma is referred to the malignant lesions of the pancreatic epithelial tumour. Case report. A 52-year-old female patient presented with pain in the umbilical and epigastric regions for 5 months and noticed a solid visible tumour on the left side of the abdomen 3 months ago when she lied down. The level of the CA125 was 47.64 U/ml (normal value <35 U/ml). Abdominal and pelvic magnetic resonance imaging (MRI) showed a cystic multiseptal mass in the left iliac region, defined as a left ovary tumour, while Computed tomography scan revealed a cystic tumour of the pancreatic tail. The patient underwent a resection of the pancreatic tail with a 20 cm cystic solid tumour, splenectomy and left hemicolectomy. Histopathology report confirmed mucinous cystic neoplasm of the pancreatic tail with associated invasive carcinoma (combined badly differentiated (G3) ductal (40%) and undifferentiated (G4) anaplastic (60%) carcinoma) pT1bN0. Postoperative course complicated with wound infection. The patient was discharged on postoperative day 10. The patient is still alive 2 years on follow-up. Conclusions. PMCN with associated invasive carcinomas are rare lesions of pancreas with relatively benign course. This malignant pancreatic tumour displays morphologies as pleomorphic epithelial cells and relatively mononuclear spindle cells, and not always tends to have underlying ovarian type stroma. The comprehensive histopathological examination of the tumour is necessary in order to cure most MCN patients with minimally invasive types

Case Report of Misleading Features of a Rare Sertoli Cell Testicular Tumor

Testicular Sertoli cell tumors are extremely rare. Generally, they are benign neoplasms, which belong to a group called sex cord−stromal tumors. In this article, we present a case report of a Sertoli cell tumor, which was accidentally discovered during a urological consultation of a 42-year-old male. An ultrasound showed a 2.1 × 2.2 cm hypoechogenic, hypervascular tumor in the middle third of the left testicle. Serum tumor markers (α-fetoprotein, alkaline phosphatase, β-human chorionic gonadotropin, and lactic dehydrogenase) were all within the normal range. Rapid microscopic evaluation of fresh frozen sections during the operation was inconclusive, which led to a decision not to perform a radical orchiectomy immediately. On formalin-fixed paraffin-embedded (FFPE) sections, the tumor histology showed atypical patterns, and immunohistochemical analysis was performed in order to determine the type of neoplasm and differentiate it from other types of testicular tumors, so as to assign the further course of treatment. Radical inguinal orchiectomy was performed. The final pathology report showed a tumor with no predictive signs of aggressive behavior, which most closely resembled a Sertoli cell tumor

Aberrant pancreas adenocarcinoma in the stomach: a case report ant literature review /

Rationale: Aberrant pancreatic tissue in the gastrointestinal tract is a relatively common finding. However, malignant transformation is extremely rare. Herein, we report a case of ectopic pancreatic ductal adenocarcinoma in the stomach wall. Patient concerns: A 38 year old male presented with nausea, bloating, abdominal distention and weight loss for 4 months. Diagnoses: Endoscopy of upper gastrointestinal tract was performed twice with 2 months interval and a stenotic pyloric part was observed with a suspected submucosal lesion. It was sampled both times, however the pathology findings of the mucosal biopsies were unremarkable with no identifiable neoplastic structures. CT scan and MRI was performed and showed a thickened pyloric wall with a submucosal lesion 15 × 15 mm in diameter. Blood levels of tumor markers carcinoembrionic antigen and carbohydrate antigen 19-9 were within a normal range. Interventions: Pyloric stenosis progressed and the patient underwent a Billroth type I distal gastric resection with D2 lymphadenectomy. Pathologic examination revealed a well differentiated ductal adenocarcinoma arising in the heterotopic pancreatic tissue (Heinrich type III). The resection margins and lymph nodes were free of tumor. The patient received adjuvant chemotherapy with 6 courses of XELOX. Outcomes: No disease recurrence is reported in 12 months follow-up. Lessons: Aberrant pancreatic ductal adenocarcinoma in the stomach is a rare finding, however this pathology should be included in the differential diagnosis of gastric submucosal lesion causing pyloric stenosis. Abbreviations: AP = aberrant pancreas, CT = computed tomography, DEAP = the CT attenuation value of arterial phase minus that of unenhanced phase, EUS = endoscopic ultrasound, EUS-FNA = endoscopic ultrasound-guided fine-needle aspiration, FOLFOX = folinic acid, fluorouracil and oxaliplatin, GST = gastric stromal tumor, R0 = resection margin free of tumor, S-1 = tegafur, gimeracil and oteracil, T3N0M0 = the gastric tumor reaches subserosa, but does not penetrate the serosa, there is no spread to lymph nodes or distant metastasis, XELOX = capecitabine and oxaliplatin

The Impact of Chemotherapy and Transforming Growth Factor-β1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients

An ongoing debate surrounds the impact of chemotherapy on post-hepatectomy liver regeneration in patients with colorectal cancer liver metastases (CRLM), with unclear regulatory mechanisms. This study sought to delve into liver regeneration post-resection in CRLM patients, specifically examining the roles of hepatocyte growth factor (HGF) and transforming growth factor β1 (TGF-β1). In this longitudinal observational study, 17 patients undergoing major liver resection for CRLM and 17 with benign indications as controls were enrolled. Liver regeneration within 30 postoperative days was assessed via CT, considering clinicopathological characteristics, liver enzymes, liver stiffness by elastography, and the impact of HGF and TGF-β1 on liver regeneration. The results revealed that the control group exhibited significantly higher mean liver regeneration volume (200 ± 180 mL) within 30 days postoperatively compared to the CRLM group (72 ± 154 mL); p = 0.03. Baseline alkaline phosphatase (AP) and TGF-β1 blood levels were notably higher in the CRLM group. Immunohistochemical analysis indicated a higher proportion of CRLM patients with high TGF-β1 expression in liver tissues compared to the control group (p = 0.034). Correlation analysis showed that resected liver volume, baseline plasma HGF, AP, and albumin levels significantly correlated with liver regeneration volume. However, in multivariable analysis, only resected liver volume (β: 0.31; 95% CI: 0.14–0.47, p = 0.01) remained significant. In conclusion, this study highlights compromised liver regeneration in CRLM patients post-chemotherapy. Additionally, these patients exhibited lower serum TGF-β1 levels and reduced TGF-β1 expression in liver tissue, suggesting TGF-β1 involvement in mechanisms hindering liver regeneration capacity following major resection after chemotherapy

Prognostic Value of CD8+ Lymphocytes in Hepatocellular Carcinoma and Perineoplastic Parenchyma Assessed by Interface Density Profiles in Liver Resection Samples

Hepatocellular carcinoma (HCC) often emerges in the setting of long-standing inflammatory liver disease. CD8 lymphocytes are involved in both the antitumoral response and hepatocyte damage in the remaining parenchyma. We investigated the dual role of CD8 lymphocytes by assessing density profiles at the interfaces of both HCC and perineoplastic liver parenchyma with surrounding stroma in whole-slide immunohistochemistry images of surgical resection samples. We applied a hexagonal grid-based digital image analysis method to sample the interface zones and compute the CD8 density profiles within them. The prognostic value of the indicators was explored in the context of clinicopathological, peripheral blood testing, and surgery data. Independent predictors of worse OS were a low standard deviation of CD8+ density along the tumor edge, high mean CD8+ density within the epithelial aspect of the perineoplastic liver-stroma interface, longer duration of surgery, a higher level of aspartate transaminase (AST), and a higher basophil count in the peripheral blood. A combined score, derived from these five independent predictors, enabled risk stratification of the patients into three prognostic categories with a 5-year OS probability of 76%, 40%, and 8%. Independent predictors of longer RFS were stage pT1, shorter duration of surgery, larger tumor size, wider tumor-free margin, and higher mean CD8+ density in the epithelial aspect of the tumor-stroma interface. We conclude that (1) our computational models reveal independent and opposite prognostic impacts of CD8+ cell densities at the interfaces of the malignant and non-malignant epithelium interfaces with the surrounding stroma; and (2) together with pathology, surgery, and laboratory data, comprehensive prognostic models can be constructed to predict patient outcomes after liver resection due to HCC

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in combination with FOLFOX chemotherapy as a first-line treatment for gastric cancer patients with peritoneal metastases: single-arm phase II study

Abstract Background Gastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment. Methods This study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6–7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228–47) in a CT scan performed 7 days after the 4th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity. Discussion This study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM. Trial registration NCT05644249. Registered on December 9, 2022

National colorectal cancer screening program in Lithuania: description of the 5-year performance on population level

We aimed to report the results of the implementation of the National Colorectal Cancer (CRC) Screening Program covering all the country. The National Health Insurance Fund (NHIF) reimburses the institutions for performing each service; each procedure within the program has its own administrative code. Information about services provided within the program was retrieved from the database of NHIF starting from the 1 January 2014 to the 31 December 2018. Exact date and type of all provided services, test results, date and results of biopsy and histopathological examination were extracted together with the vital status at the end of follow-up, date of death and date of emigration when applicable for all men and women born between 1935 and 1968. Results were compared with the guidelines of the European Union for quality assurance in CRC screening and diagnosis. The screening uptake was 49.5% (754,061 patients) during study period. Participation rate varied from 16% to 18.1% per year and was higher among women than among men. Proportion of test-positive and test-negative results was similar during all the study period—8.7% and 91.3% annually. Between 9.2% and 13.5% of test-positive patients received a biopsy of which 52.3–61.8% were positive for colorectal adenoma and 4.6–7.3% for colorectal carcinoma. CRC detection rate among test-positive individuals varied between 0.93% and 1.28%. The colorectal cancer screening program in Lithuania coverage must be improved. A screening database is needed to systematically evaluate the impact and performance of the national CRC screening program and quality assurance within the program