Zsolt Zoltan Fulop

Human epidermal growth factor receptor 2 (HER2) dysregulation contributes to tumorigenesis in gastric and gastroesophageal junction adenocarcinomas (GC/GEJ). HER2 overexpression has been associated in multiple cohorts with aggressive behavior and poor outcomes. While HER2 amplification has long guided therapy in HER2-positive disease, antibody–drug conjugates (ADCs) have shifted attention toward the HER2-low category, typically defined as immunohistochemistry (IHC) 1+ or IHC 2+ with negative in situ hybridization (ISH). This narrative review integrates evidence from the peer-reviewed literature, current testing recommendations, and registered clinical trials. It clarifies practical issues in HER2-low assessment and maps the evolving therapeutic landscape of HER2-targeted ADCs including rational combination strategies that may extend benefit beyond conventionally HER2-positive tumors. A cross-tumor perspective contrasts GC/GEJ testing and biology with the breast cancer paradigm and summarizes the importance of HER2-low expression in non-gastric malignancies. Finally, we discuss the therapeutic strategies in HER2-low GC/GEJ and highlight key safety and monitoring considerations for HER2-directed ADCs.

A hasnyálmirigy szokatlan helye a daganatos áttétek (szekunder daganatok) kialakulásának. A hasnyálmirigyet érintő áttétes megbetegedés lehet izolált vagy diffúz, míg a megjelenés alapján szinkrón vagy metakrón. A különböző szekunder pancreasdaganatok prognózisa a primer daganattól függően változó. Az irodalmi áttekintés célja, hogy képet adjon a hasnyálmirigyben kialakuló áttétekről és azok terápiás lehetőségeiről. A szakirodalom retrospektív áttekintését végeztük a 2014 és 2023 közötti időszakra vonatkozóan a PubMed adatbázis használatával. Az így nyert adatokból a szekunder pancreasdaganatokat elemeztük előfordulási gyakoriságuk, az áttétet adó elsődleges malignus daganatok, a klinikai tünetek, kórisméjük, a kialakulási mechanizmusok és a kezelési elvek alapján. A pancreas szekunder daganatai ritkák, a malignus hasnyálmirigy-daganatok 2–5%-át alkotják. A világos sejtes vesesejtes carcinoma okoz a leggyakrabban áttétet a hasnyálmirigyben. A pancreas szekunder daganatai gyakran tünetmentesek, a kórisme felállítása nehéz, összetéveszthetők a primer daganatokkal, ezért szükségesek a szövettani és immunhisztokémiai vizsgálatok. A másodlagos hasnyálmirigy-daganatok kialakulásában a szisztémás-hematogén mechanizmus az elfogadott. A sebészeti kezelés meghosszabbítja a túlélést, a szisztémás, molekuláris célzott terápia alkalmazása az utóbbi időben hatékonynak bizonyult. Orv Hetil. 2025; 166(15): 563–568.

Esophageal carcinoma is an aggressive cancer with a poor therapeutic response and a significant risk of recurrence after radical resection. It usually metastasizes to the lung, bones, or liver. Unusual spread can be found in other organs, but only nine cases of pancreatic metastases have been reported in the Medline database. In the present paper, a literature review of nine cases with esophageal squamous cell carcinoma and pancreatic metastasis was carried out. In addition to these cases, we present our case, the tenth case in the literature. It involved a patient who underwent surgery for esophageal squamous cell carcinoma and developed metachronous pancreatic metastasis 67 months after esophagectomy. Histopathological examination confirmed a squamous cell carcinoma metastasis. Conclusions: Pancreatic metastasis of esophageal squamous cell carcinoma is extremely rare. Pancreatic metastasis may develop several years after the treatment of the primary lesion. The diagnosis of metastasis is difficult, requiring histopathological and immunohistochemical examination.

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We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed. CD4⁺/CD8⁺ positivity was analyzed in 75 cases in four systematically predefined tumor regions. Immune gene expression of Met and Ctrl HER2-negative BCs was compared by using NanoString nCounter technology. The amount of TIL infiltration varied greatly within all BC subtypes. Two-third of the cases were cold tumors with no significant survival difference compared to hot tumors. A lower CD4⁺/CD8⁺ ratio at the stromal internal tumor region was significantly associated with longer distant metastasis-free survival. The differentially expressed immune genes between Met and Ctrl varied across the studied BC subtypes with TNBC showing distinct features from the luminal subtypes. The TIME is characterized by a considerable heterogeneity; however, low level of TILs does not equate to disease progression. The differences in immune gene expression observed between Met and Ctrl breast carcinomas call attention to the important role of altered immune function in BC progression.

Preoperative staging of colorectal cancer (CRC) based on imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is crucial for identification and then removal of the positive lymph nodes (LNs). The aim of this study was to evaluate the correlation between preoperatively seen morphologic criteria (number, size, shape, structure, borders, or enhancement patterns) and histopathological features of LNs using an in-house validated map of nodal stations. A total of 112 patients with CRC that underwent surgery were preoperatively evaluated by CT scans. The locoregional, intermediate, and central LNs were CT-mapped and then removed during open laparotomy and examined under microscope. The analysis of correlations was interpreted using the suspicious-to-positive ratio (SPR) parameter. The greatest correlation was found in tumors located in the sigmoid colon, descending colon and middle rectum; SPR value was 1.12, 1.18, and 1.26, respectively. SPR proved to be 0.59 for cases of the transverse colon. Regarding the enhancement type, the dotted pattern was mostly correlated with metastatic LNs (OR: 7.84; ), while the homogenous pattern proved a reliable indicator of nonmetastatic LNs (OR: 1.99; ). A total of 1809 LNs were harvested, with a median value of LNs/case. Transdisciplinary approach of CRC focused on pre-, intra-, and postoperatively mapping of LNs might increase the accuracy of detecting metastasized nodes for tumors of the distal colon and middle rectum but not for those of the transverse colon. In addition to morphologic criteria, the enhancement pattern of LNs can be used as a predictor of nodal involvement improving the CT-based preoperative staging.

Introduction: Massive ventral hernia repairs may lead to abdominal compartment syndrome, which is associated with increased morbidity and mortality, and is caused by an acute rise in intra-abdominal pressure, frequently leading to multi-organ failure and possibly death. This report presents a case with a voluminous incisional hernia associated with intestine obstruction and the issues surrounding emergency surgical treatment. Case report: An overweight 67-year-old patient with a medical history of diabetes and multiple cardiovascular pathologies presented to the emergency department complaining of abdominal distension, pain, nausea, vomiting, and lack of intestinal transit for 48 hours. A clinical diagnosis of bowel obstruction was established, caused by a large ventral hernia. During surgery, a tension free abdominal wall reconstruction was performed with a peritoneal flap from the hernia sac and retromuscular Prolene synthetic mesh. A Redon-type drainage of the posterior rectus compartment and subcutis was applied for 48 hours. After the operation, the patient was transferred to the intensive care unit for monitoring. During the follow-up, continuous monitoring of arterial blood pressure, oxygen saturation, renal function, daily diuresis, lactic acid values, and intraabdominal pressure was performed. On the 9th postoperative day, the patient was released in good general health, stable from a cardiorespiratory point of view, with a clean, healing surgical wound. Conclusion: The repair of large ventral hernias is technically challenging. The management of giant incisional hernias is complex, requiring thoughtful preoperative evaluation with CT imaging and volumetry calculation, which can help establish the surgical strategy.

Background: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. Methods: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers β-catenin and E-cadherin, same as KRAS and BRAF mutations. Results: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. Conclusions: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors.

Despite the description of several new prognostic markers, colorectal cancer still represents the third most frequent cause of cancer-related death. As immunotherapy is considered a therapeutic alternative in such patients, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratio (LMR) are hypothesized to provide reliable prognostic information. A retrospective study was conducted on 1052 patients operated on during 2013–2019 in two clinical hospitals from Hungary and Romania. Inclusion criteria targeted patients over 18 years old, diagnosed with rectal cancer, with preoperatively defined NLR and LMR. The overall survival rate, along with clinical and histopathological data, was evaluated. Overall survival was significantly associated with increased NLR (p = 0.03) and decreased LMR (p = 0.04), with cut-off values of 3.11 and 3.39, respectively. The two parameters were inversely correlated (p < 0.0001). There was no statistically significant association between tumor stage and NLR or LMR (p = 0.30, p = 0.06, respectively). The total mesorectal excision was especially obtained in cases with low NLR (p = 0.0005) and high LMR (p = 0.0009) values. A significant association was also seen between preoperative chemoradiotherapy and high NLR (p = 0.0001) and low LMR (p = 0.0001). In patients with rectal cancer, the preoperative values of NLR and LMR can be used as independent prognostic parameters. An NLR value of ≥3.11 can be used to indicate the response to preoperative chemoradiotherapy, but a low chance of sphincter preservation or obtaining a complete TME. Higher values of NLR and lower values of LMR require a more attentive preoperative evaluation of the mesorectum.