Diagnosis and Management of Duodenal Bulb Neuroendocrine Carcinoma with Liver Metastases: A Case Report and Literature Review

Summary

This case describes a rare duodenal bulb neuroendocrine carcinoma with liver metastases, highlighting its aggressive nature, diagnostic challenges, and poor response to standard chemotherapy.

Abstract

Duodenal bulb neuroendocrine carcinoma (NEC), a subtype of neuroendocrine neoplasms (NENs), is a rare, high-grade malignancy often presenting at an advanced stage. We report a 40-year-old male with epigastric pain and melena who underwent a stepwise diagnostic and therapeutic protocol. Upper gastrointestinal endoscopy identified a 3.5 × 3.0 cm ulcerative lesion in the duodenal bulb, from which multiple deep biopsies were obtained to minimize the risk of misclassification, underscoring an essential educational point for clinical practice. Histopathological examination demonstrated poorly differentiated NEC with intravascular tumor thrombi, and immunohistochemical staining confirmed neuroendocrine differentiation (CgA, Synaptophysin, CD56, CK7) with a Ki-67 index of approximately 70%. Contrast-enhanced computed tomography (CT) revealed synchronous hepatic and lymph node metastases, establishing advanced disease. Following multidisciplinary evaluation, the patient received systemic chemotherapy with etoposide and cisplatin, administered in four cycles under routine monitoring of hematologic and hepatic parameters. Despite treatment, repeat CT demonstrated progressive hepatic lesions, culminating in hepatic failure and death. This protocol not only highlights the reproducible diagnostic workflow-endoscopic biopsy, immunohistochemical profiling, and cross-sectional imaging-but also serves an educational role in reminding clinicians of the diagnostic pitfalls inherent in superficial sampling and the necessity of deep biopsies for accurate classification. The case illustrates both the methodological steps required for accurate classification of duodenal NEC and the limitations of current treatment strategies. Our report contributes to the scarce data on duodenal bulb NEC and emphasizes the importance of early recognition, systematic diagnostic procedures, and multidisciplinary management to guide future practice.

Introduction

Neuroendocrine neoplasms (NENs) are a diverse group of tumors arising from neuroendocrine cells dispersed throughout the body, primarily within the gastrointestinal tract, pancreas, and lungs¹. These tumors originate from amine precursor uptake and decarboxylation (APUD) cells, which possess both neural and endocrine characteristics, and are capable of secreting biologically active peptides and amines². Within this spectrum, NENs are categorized into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs), the latter representing the high-grade, aggressive subtype, with the latter exhibiting aggressive biological behavior, high proliferative index, and a poor clinical prognosis³.

Among gastrointestinal NENs, duodenal bulb NECs are exceedingly rare. Most duodenal NENs are well-differentiated NETs, and epidemiological series indicate that more than 70-80% of duodenal NETs occur in the ampullary region, while lesions originating in the duodenal bulb comprise only a small minority³. NECs located in the duodenal bulb-a more proximal anatomical segment-are rarely reported in the literature, making them a subject of considerable clinical interest⁴. These tumors are typically discovered at an advanced stage, frequently presenting with liver or lymph node metastases at the time of diagnosis². Consequently, the prognosis for patients with D-NEC, particularly those originating in the bulb, remains poor, and effective treatment strategies are limited.

The incidence of NENs has been increasing significantly over the past few decades, likely due to improvements in diagnostic techniques such as endoscopy, imaging modalities, and immunohistochemistry. According to data from the Surveillance, Epidemiology, and End Results (SEER) program, the incidence of NENs has increased more than six-fold, reaching approximately 7 cases per 100,000 person-years⁵. However, within this growing subset, NECs account for only about 20% of all NENs, and among these, primary duodenal bulb NECs remain an extremely rare clinical entity.

From a histopathological perspective, NECs, as poorly differentiated NENs, are characterized by high mitotic activity and elevated Ki-67 proliferation index, typically exceeding 20%^4,5. Immunohistochemical markers such as chromogranin A (CgA), synaptophysin (Syn), and CD56 are commonly positive, confirming their neuroendocrine origin^3,6. However, due to their aggressive clinical course, patients often present with vague and nonspecific gastrointestinal symptoms such as abdominal pain, melena, nausea, or even signs of gastrointestinal bleeding, which frequently delays diagnosis. Endoscopic diagnosis requires sufficient tissue sampling. Compared with superficial biopsies, which frequently miss submucosal components and may result in misclassification as adenocarcinoma, deep biopsies significantly improve the diagnostic yield and allow reliable immunohistochemical analysis⁷. For staging, contrast-enhanced computed tomography (CT) remains widely available and highly effective in detecting hepatic metastases, whereas magnetic resonance imaging (MRI) offers superior soft-tissue resolution and greater sensitivity for liver lesions, particularly those smaller than 1 cm^8,9.

Diagnosing duodenal bulb NEC poses multiple challenges. Endoscopic examination may reveal ulcerative or mass-like lesions, but the findings are often nonspecific⁴. Superficial biopsies are prone to sampling errors, and routine hematoxylin and eosin staining may misclassify the tumor as poorly differentiated adenocarcinoma. Therefore, immunohistochemical analysis is crucial for accurate diagnosis and subtyping. Imaging studies such as contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are essential for staging and for identifying metastatic spread, particularly to the liver and regional lymph nodes^2,5. Despite advances in diagnostics, there is currently no standardized treatment protocol for duodenal NECs, and reported response rates to platinum-based chemotherapy remain unsatisfactory^10,11,12. To optimize reproducibility in clinical practice, a minimum immunohistochemistry panel (CgA, Syn, CD56, and Ki-67) is recommended, supplemented by cytokeratins for differential diagnosis. A typical imaging sequence includes abdominal CT as the initial modality, followed by MRI for detailed liver evaluation and, when available, functional imaging such as 68Ga-DOTATATE PET/CT. Known limitations include the frequent difficulty of distinguishing NECs from mixed adenoneuroendocrine carcinomas and the lack of predictive biomarkers to guide therapy.

Given the limited number of cases and the absence of large-scale clinical trials, there is currently no standardized treatment protocol for D-NECs. Management strategies are often extrapolated from treatment guidelines for small-cell lung carcinoma due to shared histological features. Chemotherapy regimens such as etoposide combined with cisplatin (EP) are commonly employed in advanced or metastatic settings. However, the overall response rate remains unsatisfactory, and long-term survival is rare. Surgical resection may be curative for localized disease, but most patients are ineligible due to widespread metastasis at the time of diagnosis. Furthermore, the potential for mixed histological subtypes -- such as adenoneuroendocrine carcinomas -- complicates therapeutic decisions and prognostic evaluation.

The rarity and aggressive behavior of duodenal bulb NECs underscore the importance of increased clinical awareness and more robust documentation of individual cases⁴. Each reported case contributes valuable data to the understanding of the natural history, diagnostic pitfalls, and therapeutic response of this disease. In particular, attention should be given to immunohistochemical profiling, radiological features, treatment regimens, and follow-up outcomes to establish a more comprehensive knowledge base.

In this report, we present a case of a 40-year-old male with poorly differentiated neuroendocrine carcinoma of the duodenal bulb, accompanied by synchronous liver and lymph node metastases. The patient initially presented with nonspecific gastrointestinal symptoms, including epigastric pain and melena, and was ultimately diagnosed through endoscopic biopsy and confirmed by immunohistochemistry. Despite receiving four cycles of systemic chemotherapy with etoposide and cisplatin, the patient's condition rapidly deteriorated, culminating in liver failure and death within a short span of time. This tragic outcome illustrates the highly malignant nature of duodenal bulb NECs, a rare subtype of NENs, and the limitations of current treatment options.

The objective of this case report is threefold. First, we aim to enhance recognition of this rare disease by documenting its clinical course, diagnostic process, and treatment response. Second, we seek to highlight the challenges associated with the accurate diagnosis and management of duodenal bulb NECs, particularly in the context of advanced disease. Finally, we review the current literature to provide a contextual framework for this case and discuss emerging diagnostic and therapeutic strategies that may offer hope for future patients.

Through this comprehensive analysis, we hope to raise awareness among clinicians regarding the early signs of D-NECs, advocate for the use of multimodal diagnostic approaches -- including immunohistochemistry and cross-sectional imaging -- and underscore the urgent need for clinical trials to establish effective, evidence-based treatment protocols. As our understanding of the molecular and clinical characteristics of neuroendocrine carcinomas evolves, so too will our ability to offer patients more personalized and effective care.

CASE PRESENTATION:
A 40-year-old male was admitted in April 2023 with complaints of intermittent epigastric pain lasting for 2 months, and melena appearing 1 week prior to admission. The pain occurred without obvious triggers, worsened at night, and was relieved after food intake. The patient denied symptoms of acid reflux, heartburn, nausea, vomiting, jaundice, weight loss, or altered bowel habits. A month prior to admission, gastroscopy at a local hospital revealed a 1.5 cm ulcer in the duodenal bulb, but no biopsy was performed, and no formal report was available. The patient tested positive for Helicobacter pylori via a ¹⁴C-urea breath test and received eradication therapy along with proton pump inhibitors. However, his symptoms persisted. The patient had no significant past medical illnesses. The patient was a non-smoker, consumed alcohol occasionally, and worked in an office setting. Family history was non-contributory, with no known history of gastrointestinal malignancy or neuroendocrine disorders. On physical examination, the patient was alert and hemodynamically stable. His conjunctivae were not anemic, sclerae were non-icteric, and superficial lymph nodes were not palpable. Abdominal examination revealed a soft and non-tender abdomen with no palpable masses or organomegaly. Laboratory studies, including a complete blood count, liver and renal function tests, and tumor markers (alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and carbohydrate antigen 19-9 [CA19-9]), were within normal limits. Cross-sectional imaging with abdominal contrast-enhanced computed tomography (CT) revealed multiple hypodense nodules in the liver (the largest approximately 1.9 cm in diameter), suggestive of metastases, along with irregular soft tissue masses involving the duodenal bulb and pancreatic head, and enlarged peripancreatic lymph nodes. Further evaluation with upper gastrointestinal endoscopy showed a 3.5 cm × 3.0 cm ulcerative lesion with a white exudate and raised, edematous margins in the posterior wall of the duodenal bulb. The lesion exhibited contact bleeding. Three biopsy specimens were obtained. The patient's baseline Eastern Cooperative Oncology Group (ECOG) performance status was 1, indicating that he was ambulatory and capable of light work, with minimal restrictions on daily activities.

Diagnosis, Assessment, and Plan:
The patient was diagnosed with poorly differentiated neuroendocrine carcinoma (NEC) of the duodenal bulb with hepatic and lymph node metastases.

Upon admission, the patient underwent comprehensive laboratory testing and imaging studies. Baseline blood work revealed no significant abnormalities in liver function, renal function, electrolytes, or coagulation profile. Tumor markers, including AFP, CEA, and CA19-9, were within normal ranges, providing limited diagnostic utility. Due to the persistent symptoms and history of a duodenal ulcer, contrast-enhanced abdominal CT was performed and revealed multiple hypodense lesions in the liver with blurred margins, the largest measuring approximately 1.9 cm, consistent with metastatic deposits. In addition, there were irregular, poorly defined soft tissue masses involving the gastric antrum, duodenal bulb, and pancreatic head, with associated regional lymphadenopathy. These findings prompted further endoscopic evaluation. Upper endoscopy revealed a large (3.5 × 3.0 cm) ulcerative lesion in the posterior wall of the duodenal bulb. The lesion had a central necrotic area with a thick white coating and raised, hyperemic edges. Contact bleeding was observed. Multiple biopsy specimens were obtained from the ulcerated mass. Histopathological examination demonstrated poorly differentiated tumor cells arranged in nests and sheets, with significant nuclear atypia and high mitotic activity. Immunohistochemical staining was diffusely positive for chromogranin A (CgA), synaptophysin (Syn), CD56, and cytokeratin markers (CK7, CKpan), confirming neuroendocrine differentiation. The Ki-67 proliferation index was approximately 70%, indicating a poorly differentiated high-grade NEC^11,12. Vascular invasion and tumor thrombus formation were also noted. These histological features confirmed the diagnosis of poorly differentiated neuroendocrine carcinoma of the duodenal bulb. Given the radiologic evidence of hepatic and nodal metastases, the disease was staged as advanced and non-resectable at presentation. Differential diagnoses initially considered included poorly differentiated adenocarcinoma, lymphoma, and gastrointestinal stromal tumor (GIST); however, these were ruled out based on immunohistochemical findings and tumor morphology.

Considering the high-grade nature of the tumor and the presence of metastatic disease, surgical resection was not indicated. The multidisciplinary tumor board recommended initiating systemic chemotherapy. A standard regimen consisting of etoposide and cisplatin (EP) was selected, in accordance with existing treatment protocols for extrapulmonary NECs and by extrapolation from small-cell lung cancer management strategies. The patient underwent four cycles of EP chemotherapy, with close monitoring for hematologic toxicity and liver function. Despite treatment, follow-up imaging demonstrated progression of liver metastases with increased tumor burden. Liver function deteriorated progressively, and the patient eventually developed hepatic failure. Due to poor response to first-line chemotherapy and rapid clinical decline, second-line treatment options were considered but ultimately deemed unsuitable in light of the patient's deteriorating performance status and liver dysfunction. After discussions with the patient and his family, the decision was made to pursue palliative care. The patient was discharged home for supportive management and passed away approximately one month later. This case highlights the aggressive nature and poor prognosis of duodenal bulb NECs, even with early chemotherapy initiation. The rapid disease progression underscores the need for novel therapeutic approaches and emphasizes the importance of early recognition and accurate histopathological classification in managing neuroendocrine malignancies of the gastrointestinal tract.

Protocol

This protocol was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Hebei Provincial Hospital of Traditional Chinese Medicine. Written informed consent was obtained from the patient prior to diagnostic and therapeutic procedures. All procedures were part of routine clinical care, and no experimental intervention was performed.

1. Patient selection

1. Confirm that the patient is an adult (≥18 years) presenting with upper gastrointestinal bleeding manifested as melena and accompanied by epigastric pain.
2. Verify the presence of a duodenal bulb lesion that appears suspicious for malignancy during preliminary endoscopy.
3. Ensure that the patient's clinical condition allows tolerance of endoscopy, imaging examinations, and systemic chemotherapy.
4. Exclude any patient with contraindications to endoscopy, such as severe coagulopathy that cannot be corrected, a known allergy to iodinated contrast media, or an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or higher, indicating intolerance to chemotherapy.

2. Preoperative assessment and preparation

1. Perform a complete blood count to evaluate baseline hemoglobin, leukocyte, and platelet levels.
2. Conduct biochemical tests to assess liver and renal function, including alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, and blood urea nitrogen.
3. Obtain a coagulation profile including prothrombin time, international normalized ratio, and activated partial thromboplastin time.
4. Measure tumor markers, including AFP, CEA, and CA19-9.
5. Perform abdominal contrast-enhanced CT using a multi-detector scanner set at 120 kVp and 200-250 mAs with a 5-mm slice thickness and 1-mm reconstruction.
6. Inject 100 mL of nonionic iodinated contrast agent (iopamidol 300 mg I/mL) at 3 mL/s through an 18-20-G cannula placed in the antecubital vein.
7. Acquire arterial-phase images at 25-30 s, portal-venous-phase images at 60-70 s, and delayed-phase images at 120-150 s after injection.
8. When necessary, perform MRI using a 1.5 T system with T1- and T2-weighted sequences and diffusion-weighted imaging (b = 0/800 s/mm²) for better detection of small hepatic lesions.
9. Instruct the patient to fast for at least 8 h before the endoscopic examination.
10. Place the patient in the left lateral decubitus position, administer oxygen at 2-3 L/min through a nasal cannula, and continuously monitor the electrocardiogram, pulse oximetry, and blood pressure.
11. Administer intravenous midazolam at 0.05 mg/kg for sedation, and if deeper sedation is required, titrate propofol infusion at 25-75 µg/kg/min under an anesthesiologist's supervision.
12. Verify that emergency airway and resuscitation equipment are immediately available before starting the procedure.

3. E​ndoscopy and biopsy procedure

1. Insert a high-definition gastroscope gently through the mouth, esophagus, and stomach, and advance it into the duodenal bulb under direct vision.
2. Carefully inspect the duodenal bulb for any ulcerative or mass-like lesion and evaluate its size, shape, margin characteristics, degree of necrosis, and presence of contact bleeding.
3. Use single-use biopsy forceps compatible with a 2.8-mm channel to obtain at least three deep tissue samples from both the base and the margins of the lesion to include submucosal tissue.
4. Immediately place each biopsy specimen into 10% neutral buffered formalin at a tissue-to-fixative ratio of 1:10 and label each container according to sampling site.
5. Fix the tissues at room temperature for 12-24 h to ensure adequate penetration and preservation.
6. Verify that each specimen contains both mucosal and submucosal components under gross inspection; repeat sampling if only superficial tissue is obtained.
7. Manage any bleeding that occurs by injecting 1:10,000 epinephrine (0.5-1 mL per site) into the bleeding point or by applying argon plasma coagulation at low power.
8. Confirm complete hemostasis before removing the endoscope.

4. Histopathology and immunohistochemistry (IHC)

1. Process all fixed tissues by embedding them in paraffin blocks and cutting sections 3-4 µm thick using a rotary microtome.
2. Mount sections on poly-L-lysine-coated slides and dry them at 60 °C for 1 h.
3. Perform hematoxylin and eosin (HE) staining to evaluate basic morphology and cellular architecture.
4. Conduct antigen retrieval by immersing the slides in citrate buffer (pH 6.0) and heating them to 95 °C for 20 min, then allow them to cool to room temperature.
5. Block endogenous peroxidase activity by incubating the slides in 3% hydrogen peroxide for 10 min.
6. Incubate the sections for 1 h at room temperature with primary antibodies diluted as follows: chromogranin A (1:200), synaptophysin (1:100), CD56 (1:50), cytokeratin 7 (1:100), and Ki-67 (1:100).
7. Rinse slides with phosphate-buffered saline between steps to remove unbound reagents.
8. Apply a horseradish-peroxidase-conjugated secondary antibody for 30 min.
9. Develop the reaction with 3,3′-diaminobenzidine (DAB) for 2-5 min until brown chromogenic deposition appears and counterstain with hematoxylin.
10. Dehydrate the slides through graded alcohols, clear them in xylene, and mount with neutral resin.
11. Include a known neuroendocrine carcinoma sample as a positive control and omit the primary antibody for a negative control.
12. Confirm the diagnosis of poorly differentiated neuroendocrine carcinoma when tumor cells show diffuse positivity for synaptophysin, chromogranin A, and CD56, together with a Ki-67 proliferation index exceeding 20%.

5. Imaging workflow

1. Perform baseline CT or MRI to determine disease stage before initiating therapy.
2. Record the dimensions of the duodenal bulb lesion, note any invasion of adjacent structures, and document the presence and size of hepatic and lymph-node metastases.
3. Use MRI with diffusion-weighted imaging if CT is inconclusive for lesions smaller than 1 cm.
4. Confirm metastatic disease when multiple hypodense nodules are visible on portal-venous-phase CT images and correlate the findings with clinical and histologic results.

6. Chemotherapy administration

1. Prepare the standard etoposide-cisplatin (EP) regimen consisting of etoposide 100 mg/m² intravenously on days 1-3 and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days as one cycle.
2. Dilute etoposide in 250 mL of 0.9% sodium chloride or 5% glucose and infuse it over 1 hour using an in-line filter.
3. Dilute cisplatin in 500 mL of 0.9% sodium chloride and infuse it over 3-4 h with adequate hydration.
4. Administer pre- and post-cisplatin hydration with 2-3 L of isotonic saline supplemented with 20 mEq of potassium chloride and 8 mEq of magnesium sulfate.
5. Provide antiemetic prophylaxis with ondansetron 8 mg intravenously, dexamethasone 12 mg intravenously, and aprepitant 125 mg orally on day 1 before chemotherapy.
6. Prepare and handle all cytotoxic agents inside a certified Class II B2 biological safety cabinet, and require staff to wear double nitrile gloves, impermeable gowns, and protective eyewear.
7. Dispose of all contaminated materials in yellow-labeled cytotoxic waste containers and incinerate them at or above 1100 °C according to WHO 2014 (https://apps.who.int/iris/bitstream/handle/10665/85349/9789241548564_eng.pdf?utm_source=chatgpt.com) and OSHA 2016 (https://www.osha.gov/hazardous-drugs/controlling-occex?utm_source=chatgpt.com) guidelines for hazardous-drug disposal.
8. Adjust or delay chemotherapy doses in the event of grade ≥3 hematologic or non-hematologic toxicity according to institutional protocols.

7. Post-treatment monitoring and follow-up

1. Evaluate the patient's complete blood count, electrolytes, renal function, and hepatic function before each chemotherapy cycle.
2. Monitor for treatment-related adverse effects such as febrile neutropenia, mucositis, nausea, vomiting, nephrotoxicity, and hepatotoxicity during hospitalization.
3. Obtain abdominal CT scans after every two chemotherapy cycles using the same imaging parameters as baseline to assess response and progression.
4. Document any increase in the number or size of hepatic lesions as evidence of disease progression.
5. Schedule outpatient follow-up visits at 1 month, 3 months, and 6 months after treatment initiation.
6. Record key outcome measures, including progression-free survival, overall survival, and the occurrence of hepatic failure.
7. Provide supportive care or transition to palliative management if hepatic function deteriorates or the patient becomes intolerant to chemotherapy.

Results

Successful diagnostic endoscopy revealed a 3.5 × 3.0 cm ulcerative lesion in the posterior wall of the duodenal bulb with elevated, friable mucosa and active contact bleeding (Figure 1A). Histological examination of biopsy specimens confirmed a poorly differentiated neuroendocrine carcinoma with intravascular tumor thrombi. Immunohistochemical staining demonstrated positive expression of neuroendocrine markers, including Synaptophysin, Chromogranin A, CD56, and CK7, with a Ki-67 proliferatio...

Discussion

Neuroendocrine carcinomas (NECs) of the duodenum are rare, accounting for less than 2% of all duodenal neoplasms, with the majority arising in the ampullary region⁶. NECs of the duodenal bulb are exceedingly uncommon and frequently diagnosed at an advanced stage. Due to their rapid progression, strong heterogeneity, and often asymptomatic early course, they pose significant diagnostic and therapeutic challenges. In this case, the patient presented with melena and vague epigastric discomfort, and t...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
10% Neutral Buffered Formalin	Solarbio Life Sciences	G2161	Used for tissue fixation (12–24 h at room temperature, ratio 1:10).
Aprepitant Capsules	Merck & Co., Inc.	NDC 0006-3069-32	Oral NK1 receptor antagonist for antiemetic prophylaxis.
Biopsy Forceps (single-use)	Olympus Co., Ltd.	FB-25K-1	Compatible with a 2.8-mm channel; used for deep biopsy sampling from lesion base and margins.
CD34 Antibody	HUABIO	ET1606-11	Endothelial marker (vascularity control).
CD56 Antibody	HUABIO	ET1702-43	Neural cell adhesion molecule marker.
Chromogranin A Antibody (CgA)	HUABIO	HA600016	Marker for neuroendocrine differentiation.
Cisplatin	Bristol Myers Squibb	4291401A1089_1_09	Platinum-based chemotherapeutic agent; used in combination with etoposide.
Citrate Buffer (pH 6.0)	Beyotime Biotechnology	P0081	Used for antigen retrieval (95 °C for 20 min).
Class II B2 Biological Safety Cabinet	Thermo Fisher Scientific	1300 Series A2	Used for preparation of cytotoxic drugs.
CT Scanner	Siemens Co., Ltd.	SOMATOM Force	Used for contrast-enhanced CT of abdomen and staging; identified hepatic and nodal metastases.
Cytokeratin 7 Antibody (CK7)	HUABIO	ET1611-59	Marker for epithelial origin confirmation.
Cytotoxic Waste Container (yellow-labeled)	Medline	DYND30280H	Used for hazardous drug disposal per WHO/OSHA guidelines.
DAB Chromogen Kit	DAKO (Agilent Technologies)	K3468	For chromogenic visualization during IHC.
Dexamethasone Injection	Tianjin Kingyork Group	H12092034	Antiemetic and anti-inflammatory premedication.
EnVision HRP-conjugated Secondary Antibody	DAKO (Agilent Technologies)	K4007	Used for IHC signal detection.
Etoposide	Pfizer	21-321	Topoisomerase II inhibitor; part of EP chemotherapy regimen.
Gastroscope	Olympus Co., Ltd.	GIF-H290	Used for diagnostic endoscopy of the duodenal bulb to visualize a 3.5 cm × 3.0 cm ulcerative lesion; multiple deep biopsies obtained.
Hematoxylin and Eosin Staining Kit	Solarbio Life Sciences	G1120	For general histopathological staining.
Hydrogen Peroxide (3%)	Sinopharm Chemical Reagent Co., Ltd.	10009218	Used to block endogenous peroxidase.
Ki-67 Antibody	HUABIO	EM1705-40	Used to determine tumor proliferation index.
MRI Scanner	GE Healthcare	Signa Explorer 1.5 T	Used for small hepatic lesion detection via diffusion-weighted imaging.
Nitrile Gloves (double)	Ansell Healthcare	92-600	Used for handling cytotoxic materials safely.
Nonionic Iodinated Contrast (Iopamidol 300 mg I/mL)	Bracco Imaging S.p.A.	113410	Intravenous contrast for CT (100 mL at 3 mL/s).
Ondansetron Injection	GlaxoSmithKline	57243-130-30	Antiemetic prophylaxis prior to chemotherapy.
Poly-L-lysine Coated Slides	Thermo Fisher Scientific	P0425	Used for mounting tissue sections prior to immunohistochemistry.
Rotary Microtome	Leica Biosystems	RM2235	Used for sectioning paraffin-embedded tissues into 3–4 μm slices.
Sodium Chloride Injection (0.9%)	China Otsuka Pharmaceutical Co., Ltd.	H20093895	Used as diluent for cisplatin and etoposide infusions.
Synaptophysin Antibody (Syn)	HUABIO	ET1606-56	Marker for neuroendocrine differentiation.
Xylene and Graded Alcohols	Sinopharm Chemical Reagent Co., Ltd.	10009217	Used for dehydration and clearing of slides.