Biliary Tract Tumors Research Articles

Unveiling the Tumor Microenvironment Through Fibroblast Activation Protein Targeting in Diagnostic Nuclear Medicine: A Didactic Review on Biological Rationales and Key Imaging Agents

The tumor microenvironment (TME) is a dynamic and complex medium that plays a central role in cancer progression, metastasis, and treatment resistance. Among the key elements of the TME, cancer-associated fibroblasts (CAFs) are particularly important for their ability to remodel the extracellular matrix, promote angiogenesis, and suppress anti-tumor immune responses. Fibroblast activation protein (FAP), predominantly expressed by CAFs, has emerged as a promising target in both cancer diagnostics and therapeutics. In nuclear medicine, targeting FAP offers new opportunities for non-invasive imaging using radiolabeled fibroblast activation protein inhibitors (FAPIs). These FAP-specific radiotracers have demonstrated excellent tumor detection properties compared to traditional radiopharmaceuticals such as [18F]FDG, especially in cancers with low metabolic activity, like liver and biliary tract tumors. The most recent FAPI derivatives not only enhance the accuracy of positron emission tomography (PET) imaging but also hold potential for theranostic applications by delivering targeted radionuclide therapies. This review examines the biological underpinnings of FAP in the TME, the design of FAPI-based imaging agents, and their evolving role in cancer diagnostics, highlighting the potential of FAP as a target for precision oncology.

A Pathological Assessment of the Microvasculature of Biliary Tract Neoplasms Referring to Pre-Existing Blood Vessels and Vessel Co-Option.

There are several types of microvasculature supplying neoplasms: "newly formed blood vessels" (neoangiogenesis), which are a component of the tumor microenvironment (TME) of invasive carcinoma with wound healing-like reaction; and "pre-existing blood vessels", which are used as tumor-supplying vessels by neoplasms (co-option vessels) and are likely to develop in hypervascularized organs. We herein review the microvasculature of neoplasms of biliary tract with reference to pre-existing vessels and vessel co-options. In the hepatobiliary system, intrahepatic large and extrahepatic bile ducts (large bile ducts) and the gallbladder as well as hepatic lobules are highly vascularized regions. In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia-PCP alignment, whereas the hepatocyte-sinusoid alignment composes hepatic lobules. Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are the main biliary tract carcinomas. CCA is subdivided into distal (d/CCA), perihilar (pCCA), and intrahepatic (iCCA), and iCCA is subdivided into small duct type (SD-iCCA) and large duct type (LD-iCCA). High-grade biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of LD-iCCA, p/dCCA, and GBC. In the large bile ducts and gallbladder, all cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while p/dCCA, LD-iCCA, and GBC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma, a unique microvasculature different from that of co-option or neoangiogenesis. Regarding iCCA showing invasion into the hepatic lobules, some SD-iCCAs replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of malignant progression and of vascular supply in CCAs and its precursors.

No communication between the bile duct and intraductal papillary neoplasm of the bile duct on imaging.

As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy.

The spectrum of pathogens and their resistance in patients with malignant liver and biliary tract tumors with biliary obstruction after extensive liver resections

The spectrum of pathogens and their resistance in patients with malignant liver and biliary tract tumors with biliary obstruction after extensive liver resections

Second line chemotherapy for advanced biliary cancer: FOLFOX versus FOLFIRI: Analysis of retrospective and prospective data

Aim. To evaluate the efficacy and toxicity of second-line polychemotherapy according to FOLFOX or FOLFIRI regimen in patients with biliary tract tumours after progression during first-line chemotherapy (CT). Materials and methods. The study is based on the analysis of retrospective and prospective data on the examination and treatment of 94 patients with biliary cancer of grades T1-4N0-2M0-1 followed-up and treated at the N.N. Blokhin National Medical Research Center of Oncology from 2015 to 2023. All patients were divided into 2 groups: Group 1 (FOLFOX, n=47) and Group 2 (FOLFIRI, n=47). In Group 1, patients received the recommended FOLFOX second-line CT regimen. Patients in Group 2 received FOLFIRI regimen. The endpoints were overall survival (OS) and incidence of grade 3-4 adverse events. Results. The study included 94 patients. In the FOLFOX group, the median OS was 13.0 months (1-year OS was 57.8±7.4%); for the FOLFIRI group, the median OS was 12.3 months (1-year OS was 54.4±7.3%). The toxicity profiles of FOLFOX and FOLFIRI were acceptable and consistent with those reported for the regimens. According to the grade 3–4 toxicity data, diarrhea was significantly more common in the FOLFIRI group (p=0.014), and neurotoxicity was more common in the FOLFOX group (p=0.006). During the second-line CT, the frequency of grade 1–4 toxicities in the groups did not differ: 18 (38.3%) events in the FOLFOX group and 19 (40.0%) events in the FOLFIRI group. Conclusion. Our results of evaluating the efficacy and toxicity of the second-line polychemotherapy regimens show that the FOLFOX and FOLFIRI CT regimens have equal efficacy in patients with advanced biliary tract cancer with a good performance according to the ECOG scale, who previously received the first-line therapy with a combination of gemcitabine with a platinum agent (cisplatin or oxaliplatin); also, our data demonstrate similar toxicity profiles of these regimens.

Is the Prognostic Nutritional Index a Novel Prognostic Factor in Patients With Unresectable/Metastatic Gallbladder and Cholangiocarcinoma Receiving Chemotherapy?

Gallbladder and biliary tract tumors are rare but highly fatal cancers. In patients diagnosed with unresectable/metastatic gallbladder cancer and cholangiocarcinomas, systemic chemotherapy is recommended if the patient's performance is good. Randomized studies on this subject are limited, and there is no standard treatment choice. The prognostic nutritional index (PNI) is a measurement calculated using albumin and absolute lymphocyte value, reflecting the immunological and nutritional status of the cancer patient. The aim of our study is to evaluate the prognostic effectiveness of PNI in unresectable/metastatic gallbladder and biliary tract cancers. The PNI was calculated using albumin and lymphocyte values at the time of diagnosis (10 x albumin g/dL + 0.005 x total lymphocyte/mm3). The relationship between PNI and overall survival (OS) and progression-free survival was examined. The prognostic nutritional index means of the patients included in the study was 44.8 (95% CI: 42.9-46.7), and the median was 44.77 (minimum: 22, maximum: 61.4). Receiver operating characteristic (ROC) analysis demonstrated a statistically significant prediction of patients' OS when the prognostic nutritional index was < 44 (AUC: 0.715, sensitivity: 54.8%, specificity: 33.3%; p=0.08). We evaluated the prognostic effectiveness of PNI in the subgroup of patients who could receive chemotherapy. In patients receiving chemotherapy, median survival was found to be 8.93 months in the PNI < 44 groups, while median survival was found to be 12.58 months in the PNI ≥44 group. The difference between both groups was statistically significant (p = 0.01). In univariate analysis, the Eastern Cooperative Oncology Group (ECOG) performance status, cancer antigen 19.9 (Ca 19.9), and PNI were statistically significant variables in predicting OS (p < 0.05). In multivariate analysis, the ECOG performance status, cancer antigen 19.9 (Ca 19.9), and PNI were found to be independent factors in predicting OS (p < 0.05). We believe that PNI can be used as a marker to assist the clinician in evaluating the prognosis of patients in the clinic and predicting treatment tolerance.

The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA's early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA.

Current interventional options for palliative care for patients with advanced-stage cholangiocarcinoma.

Primary biliary tract tumors are malignancies that originate in the liver, bile ducts, or gallbladder. These tumors often present with jaundice of unknown etiology, leading to delayed diagnosis and advanced disease. Currently, several palliative treatment options are available for primary biliary tract tumors. They include percutaneous transhepatic biliary drainage (PTBD), biliary stenting, and surgical interventions such as biliary diversion. Systemic therapy is also commonly used for the palliative treatment of primary biliary tract tumors. It involves the administration of chemotherapy drugs, such as gemcitabine and cisplatin, which have shown promising results in improving overall survival in patients with advanced biliary tract tumors. PTBD is another palliative treatment option for patients with unresectable or inoperable malignant biliary obstruction. Biliary stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary obstruction. Surgical interventions, such as biliary diversion, have traditionally been used as palliative options for primary biliary tract tumors. However, biliary diversion only provides temporary relief and does not remove the tumor. Primary biliary tract tumors often present in advanced stages, making palliative treatment the primary option for improving the quality of life of patients.

The role of molecular diagnostics in the choice of therapy for biliary tract cancers

The aim of the study was to assess the frequency and clinical significance of various molecular genetic aberrations in biliary tract tumors and to determine the optimal methods of their testing. Material and Methods. We searched the literature sources containing information on predictive molecular markers relevant for the choice of therapy in biliary tract tumors in PubMed and eLibrary databases for the period from 2010 to 2023. data from 60 studies were included in this review. Results. Biliary tract tumors are characterized by poor prognosis and low sensitivity to major systemic therapies. Nevertheless, the emergence of new targeting drugs and prescription of therapy based on the results of molecular genetic analysis can increase the life expectancy and improve the quality of life of a significant proportion of patients. The most frequently detected clinically significant abnormalities in all biliary tract tumors include HER2 gene amplification/hyperexpression (5–20 % of cases), microsatellite instability (1–2 % of cases), BRAF V600E oncogene mutation (1–2 % of cases) and KRAS G12C oncogene mutation (about 1 % of cases). Specific targetable abnormalities unique to intrahepatic cholangiocarcinomas include aberrations in the gene encoding fibroblast growth factor receptor 2, FGFR2 (10–20 % of cases) and mutations in the gene encoding the enzyme isocitrate dehydrogenase 1, IDH1 (5–30 % of cases). Very rare clinically significant molecular markers for biliary tract tumors include translocations involving the receptor tyrosine kinase genes NTRK1-3, RET, ALK and ROS1. Mutations in the genes of the dNA double-strand break repair system by the mechanism of homologous recombination are also potentially significant for the choice of therapy. First of all, these are BRCA1/2 genes, hereditary mutations in which, according to two studies, are characteristic of 5–7 % of patients with biliary cancer. Although a significant part of the above-mentioned disorders can be detected by traditional molecular biological approaches such as PCR, IHC, FISH and Sanger sequencing, a comprehensive analysis of all molecular markers of predictive value in biliary tract tumors is difficult to perform without the help of next-generation sequencing (NGS). Conclusion. To improve treatment outcomes of patients with advanced and metastatic biliary tract cancer by individualizing drug therapy, it is necessary to perform comprehensive molecular genetic analysis of tumour tissue.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

Assessment of the diagnostic significance of endoscopic ultrasonography in the differential diagnosis of formations of the hepatopancreatoduodenal zone

Purpose of the work. To study the structure of the hepatopancreaticoduodenal zone (HPD) masses according to the endosonographic picture and to estimate the diagnostic informativeness of endoscopic ultrasonography (EUS) in diagnostics of these masses in comparison with ultrasound examination of HPD (ultrasound of HPD) and computer tomography of abdominal cavity organs (CT of OBP) with contrasting. Materials and Methods. A retrospective analysis of medical records of 71 patients with GDZ masses who underwent inpatient treatment in the department of abdominal surgery and applied for diagnostic purposes to the endoscopic centre of Karaganda Multidisciplinary Hospital No.3 for EUS for the period from January 2021 to December 2022 was carried out. Results and discussion. Sensitivity of EUS in differential diagnostics of PG tumours, hepaticocholedochal dilatation, vascular invasion and metastasis to regional lymph nodes was 85%, 94,12%, 64,71% and 100% respectively, specificity - 95,93%, 100%, 80% and 92% respectively. Conclusion. Correct assessment of all manifestations of a tumour influences the choice of treatment tactics and consequently its immediate and long-term results. EUS is an effective method of differential diagnostics of pseudocysts and cystic tumours of PG, tumours of large duodenal papilla (LDP), as well as biliary tract neoplasms.

The role of durvalumab in the treatment of biliary tract tumors

Malignant biliary tract tumors are highly aggressive, with a 5-year survival rate in advanced disease 2–7%. During last decade therapeutic options for treatment biliary cancer were extremely limited. The unchanged standard of first-line therapy since 2010, based on ABC-02 trial, has been GemCis combination. The TOPAZ-1 phase III trial for the first time for last 12 years reported a survival benefit with the antiprogrammed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer, achieving a median survival of 12.9 months (11.6–14.1) compared to 11.3 months (10.1–12.5) in the placebo group (RR 0.76 [0.64–0.91]). The objective response rate was 26.7% in the durvaulmab group compared with 18.7% in the placebo group. Median of overall survival is highly dependent on the best antitumor response achieved, with patients in the durvalumab group with a partial/complete response having a median survival of 19.5 months (95% CI: 15.7–28.3), with stable disease 13.6 months (95% CI: 12.2–14.7), and with progression disease 5.7 months (95% CI: 3.6–8.9). This article describes the features of the tumor microenvironment and immunogenicity of cholangiocarcinomas, provides studies of the early phases of immunotherapy with durvalumab and tremelimumabm, and provides a detailed analysis of the key study TOPAZ-1. In addition, we describe a clinical case that demonstrates long-term disease of advanced cholagiocarcinoma due to impact of significant advances in the modern treatment of cholangiocarcinoma with the introduction of immunotherapy with durvalumab, targeted therapy and the use of a new technique of local radioembolization.

MFOLFOX-HAIC+lenvatinib+PD-1 inhibitors versus GC/GS/GEMOX chemotherapy as a first line therapy for advanced biliary tract cancer: A single-center retrospective cohort study.

Biliary tract tumors (BTC) account for about 3% of all digestive system tumors, with rising incidence and limited treatment options, particularly for advanced stages, underscoring the need for innovative therapies. This retrospective cohort study evaluated the safety and efficacy of a novel regimen combining hepatic artery infusion chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-HAIC) alongside lenvatinib and programmed cell death protein-1 (PD-1) inhibitors (mFOLFOX-HAIC+lenvatinib+PD-1i) compared to standard regimens of gemcitabine plus cisplatin, gemcitabine plus S1, or gemcitabine plus oxaliplatin (GC/GS/GEMOX) in advanced BTC patients treated from March 2019 to November 2023. A total of 89 patients were analyzed, with 55 receiving hepatic arterial infusion chemotherapy and 34 receiving the GC/GS/GEMOX regimens. Among these, 23 patients were in the mFOLFOX-HAIC+lenvatinib+PD-1i group, while 24 were in the GC/GS/GEMOX group. The median progression-free survival (mPFS) for the mFOLFOX-HAIC+lenvatinib+PD-1i group was 15 months compared to 6 months for the GC/GS/GEMOX group. Similarly, the median overall survival (mOS) was 20 months for the mFOLFOXHAIC+lenvatinib+PD-1i group versus 13 months for the GC/GS/GEMOX group. The objective response rate (ORR) and disease control rate (DCR) for the mFOLFOX-HAIC+lenvatinib+PD-1i group were 48.5% and 87.0%, respectively, both significantly higher than those observed in the GC/GS/GEMOX group at three months of treatment. The incidence of adverse events (AEs) was similar between the mFOLFOX-HAIC+lenvatinib+PD-1i group and the GC/GS/GEMOX group, at 86.5% and 84.2%, respectively, with no statistically significant difference in complication rates. Overall, mFOLFOX-HAIC+lenvatinib+PD-1i appears to be a safe and well-tolerated treatment for advanced BTC, demonstrating superior mPFS and mOS compared to standard regimens.

A rare case of Mucinous Cystic Neoplasm of Biliary tract arising from CBD

A rare case of Mucinous Cystic Neoplasm of Biliary tract arising from CBD

Amurensin G Sensitized Cholangiocarcinoma to the Anti-Cancer Effect of Gemcitabine via the Downregulation of Cancer Stem-like Properties.

Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with a high mortality rate and refractoriness to chemotherapy. Gemcitabine is an anti-cancer chemotherapeutic agent used for CCA, but the efficacy of gemcitabine in CCA treatment is limited, due to the acquisition of chemoresistance. The present study evaluated the chemosensitizing effects of Amurensin G (AMG), a natural sirtuin-1 inhibitor derived from Vitis amurensis, in the SNU-478 CCA cells. Treatment with AMG decreased the SNU-478 cell viability and the colony formation ability. Annexin V/ Propidium iodide staining showed that the AMG increased apoptotic death. In addition, AMG downregulated anti-apoptotic Bcl-2 expression, while upregulating pro-apoptotic cleaved caspase-3 expression. Treatment with AMG decreased the migratory ability of the cells in a wound healing assay and transwell migration assay. It was observed that AMG decreased the gemcitabine-induced increase in CD44highCD24highCD133high cell populations, and the expression of the Sox-2 protein was decreased by AMG treatment. Co-treatment of AMG with gemcitabine significantly enhanced the production of reactive oxygen species, as observed through mitochondrial superoxide staining, which might be associated with the downregulation of the Sirt1/Nrf2 pathway by AMG. These results indicate that AMG enhances the chemotherapeutic ability of gemcitabine by downregulating cancer stem-like properties in CCA cells. Hence, a combination therapy of AMG with gemcitabine may be an attractive therapeutic strategy for cholangiocarcinoma.

Application of Power PICC for injection of contrast agent for contrast-enhanced CT scan in patients with biliary tract tumors

Application of Power PICC for injection of contrast agent for contrast-enhanced CT scan in patients with biliary tract tumors

Exploring the Promise of Second-Line Chemotherapy in Biliary Tract Tumours: A Glimpse into Novel Treatment Approaches

Exploring the Promise of Second-Line Chemotherapy in Biliary Tract Tumours: A Glimpse into Novel Treatment Approaches

Septic shock and biliary sepsis: 90-day mortality and associated risk factors

BackgroundBiliary sepsis is common in patients with digestive cancer. Recommendations call for antibiotic de-escalation (ADE) as a strategy for antibiotic treatment of sepsis or septic shock. The aim of this study was to identify factors influencing 90-day mortality and to evaluate the impact of ADE. MethodsThis retrospective study was conducted between November 2008 and December 2019 in a referral cancer center. Adults with biliary sepsis or septic shock admitted to the ICU were included. Variables associated with 90-day mortality were identified using univariate and multivariate Cox proportional hazards models. Results122 patients were included. The 90-day mortality was 30.3% (n = 37). After multivariate analysis, the factors independently associated 90-day mortality were metastatic stage (p = 0.004), biliary tract tumour compression (p = 0.001), multi drug resistant (MDR) bacteria carriage on intensive care unit (ICU)admission (p = 0.048), serum lactate on ICU admission (p < 0.001), the use of extra-renal replacement (p = 0.008), factor V < 50% (p = 0.009) and performance status (ECOG-PS) > 2 (p < 0.001). ADE of the pivotal antibiotic (p = 0.041) and recent cancer surgery (p < 0.001) appeared to be associated with survival. ConclusionThe 90-day mortality of biliary sepsis seems to be favourable. The 90-day mortality is associated with organ dysfunctions, but also with ECOG-PS, cancer stage, MDR bacteria colonisation. ADE seems to be safe.

Squamous cell carcinoma of the cystic duct: A case report and literature review.

Pure squamous cell carcinoma (SCC) of the gallbladder is a rare malignant biliary tract tumor predominantly found in the body and neck of the gallbladder. However, its occurrence in the cystic duct is even rarer. Given its rarity, no established guidelines or consensus currently exist regarding the treatment of pure SCC of the gallbladder. We report an unusual case of SCC originating from the cystic duct with the intent of providing insights into the therapeutic approach for this type of malignancy. A male patient presented to our hospital with acute cholecystitis. Unexpectedly, imaging revealed gallbladder malignancy. Pathologic examination after surgery confirmed SCC of the cystic duct. Despite elevated bilirubin levels, we were able to exclude hilar involvement, enabling radical tumor resection. Intraoperatively, we discovered that the tumor was located in the cystic duct, a site associated with a high likelihood of invasion into neighboring organs. The tumor demonstrated a predominantly exophytic growth pattern, which prompted us to refrain from extending the resection range, thereby striking a balance between complete tumor removal and surgical trauma. We performed liver wedge resection only to ensure a negative resection margin while preserving the anatomical structure to the greatest extent possible. Postoperative recovery was rapid and uncomplicated. Pathological examination confirmed pure SCC, which led us to initiate a regimen of nab-paclitaxel and cisplatin, which is known to be effective in other organ SCCs. Remarkably, the patient experienced a rare and severe posttreatment cardiovascular event. Consequently, we switched the patient to a chemotherapy regimen of gemcitabine and cisplatin, which ultimately yielded positive clinical outcomes. no evidence of tumor recurrence was observed within 1 year after surgery. The diagnosis and therapeutic strategy for rare tumors such as gallbladder SCC should be meticulously tailored based on their unique characteristics to optimize postoperative patient outcomes.

A Novel Mutation of MSH2 Gene in a Patient with Lynch Syndrome Presenting with Thirteen Metachronous Malignancies.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), accounts for 2-3% of all colorectal cancers. This autosomal dominant disorder is associated with a predisposition to endometrial, stomach, small bowel, pancreatic, biliary tract, ovary, urinary tract, brain, and skin tumors. Lynch syndrome is caused by the mutation of the MLH1, MSH2 (EPCAM), MSH6, and PMS2 genes. In this article, a case study of a 70-year-old female patient with Lynch syndrome is presented. Over a span of 30 years, the patient underwent multiple surgical procedures for a total of thirteen different malignancies. She was found to have a deleterious pathogenic gene MSH2 (NM_000251.2) variant (mutation) c.1774_1775insT in the 12th exon. This variant, c.1774_1775insT, represents a novel finding, as it has not been previously reported in existing databases or literature. No other case of 13 metachronous tumors in a patient with Lynch syndrome was found in the literature.