bubble_chart Overview

Pancreatic islet cell carcinoid is a tumor originating from EC cells, capable of secreting hormones such as serotonin (5-HT) or 5-hydroxytryptophan (5-HTP). Some patients may clinically present with carcinoid syndrome, which is a low-grade malignant tumor with slow growth. As early as 1907, Oberndorfer first proposed that carcinoid was a slow-growing intestinal adenocarcinoma and introduced the term "carcinoid." In 1953, Lembeck discovered the presence of 5-hydroxytryptamine in carcinoid tissues, identifying it as the bioactive substance responsible for carcinoid syndrome. Williams classified carcinoids into three types: foregut, midgut, and hindgut. Foregut carcinoids secrete 5-HT, 5-HTP, vasoactive intestinal peptide, and polypeptide hormones, leading to atypical carcinoid syndrome. Midgut carcinoids, such as appendiceal carcinoids, secrete 5-HT and exhibit typical carcinoid syndrome. Hindgut carcinoids are mostly non-functional. Unlike midgut carcinoids, pancreatic islet cell carcinoids do not necessarily indicate liver metastasis when carcinoid syndrome occurs.

bubble_chart Pathological Changes

EC cells possess the characteristics of APUD cells and are widely distributed in the gastrointestinal tract, pancreas, and lungs. When the carcinoid tumor is small, with a diameter not exceeding 3.5 cm, it generally does not cause symptoms or signs. However, when the carcinoid tumor grows larger, it produces large amounts of amines and peptide hormones such as 5-HT, overwhelming the liver's ability to effectively metabolize and inactivate these secretory products. As a result, substances like 5-HT, 5-HTP, bradykinin, and pancreatic polypeptide enter the systemic circulation. Additionally, when the carcinoid tumor metastasizes to the liver, the hormones secreted by the metastatic lesions can bypass hepatic metabolism and directly enter the systemic circulation, acting on target cells and leading to the manifestation of carcinoid syndrome.

bubble_chart Clinical Manifestations

Pancreatic islet cell carcinoid may present with typical carcinoid syndrome manifestations: paroxysmal flushing of the complexion, hypotension, periorbital edema, and tearing, among others.

1. Intermittent flushing: Primarily occurs in exposed areas such as the face, neck, and anterior chest, but may also affect the entire body. The flushing episodes are typically paroxysmal and sudden, appearing bright red or dark red, and lasting from a few minutes to 1–2 days. However, the color changes may be less noticeable in individuals with darker skin or of Black ethnicity. With prolonged disease, fixed skin changes may develop in frequently affected areas, characterized by multiple fine telangiectasias and a dark red hue. Factors influencing flushing episodes include alcohol consumption, pain, emotional stress, and physical activity, which can trigger flushing. Epinephrine and norepinephrine may also exacerbate episodes, while α-adrenergic blockers can prevent them. During flushing episodes, patients often experience tachycardia, hypotension, periorbital edema, and gastrointestinal or pulmonary symptoms.

2. Cardiovascular symptoms: During flushing episodes, patients may experience tachycardia, hypotension, or even shock. Advanced stages may lead to valvular heart disease or congestive right heart failure.

3. Respiratory symptoms: In 20–30% of patients, paroxysmal flushing may be accompanied by asthma-like symptoms such as wheezing and dyspnea, caused by bronchial smooth muscle spasms induced by substances like 5-HT.

4. Gastrointestinal symptoms: Patients may experience varying degrees of abdominal pain, distension, and diarrhea. Abdominal pain is often related to the primary tumor and/or metastatic lesions, as well as compression or destruction of surrounding tissues by the growing tumor. Diarrhea is typically watery and may be severe, with 10–20 episodes per day, necessitating differentiation from WDHA syndrome.

5. Periorbital edema, conjunctival hemorrhage, and tearing often accompany skin flushing.

6. Other symptoms: Pancreatic islet cell carcinoid may also manifest as hyperfunction of other endocrine hormones, such as insulin, glucagon, growth hormone, parathyroid hormone, or adrenocorticotropic hormone, each with characteristic features for differentiation. In advanced stages, cachexia may develop, presenting as weight loss, anemia, and hypoalbuminemia.

bubble_chart Auxiliary Examination

1. Preliminary Screening Test

Place a drop of the patient's urine on filter paper, then add diazo-P-nitroaniline. If a red color appears, it indicates an increase in urinary 5-hydroxyindoleacetic acid (5-HIAA), supporting the diagnosis of this disease; if the color is purple, it suggests pheochromocytoma.

2. Measurement of Urinary 5-HIAA

Since 99% of 5-HT in the body is converted into 5-HIAA and excreted in urine, measuring the total 24-hour urinary 5-HIAA aids in diagnosing this condition. The normal range for 24-hour urinary 5-HIAA is 10.5–42.0 μmol. Most patients exhibit urinary 5-HIAA levels greater than 158 μmol/24 hours, and levels exceeding 263 μmol/24 hours have confirmatory diagnostic value.

3. Measurement of 5-HT in Tumor Tissue

The 5-HT content in carcinoid tissue is significantly elevated, making this method more sensitive than urinary 5-HIAA measurement.

Imaging techniques such as ultrasound, CT, MRI, and ERCP help determine the location, size, and number of pancreatic islet cell carcinoids, providing essential diagnostic information for surgical planning.

bubble_chart Diagnosis

In the early stages, the disease is often asymptomatic or lacks specific clinical symptoms. When a patient presents with typical paroxysmal skin flushing and recurrent episodes that are refractory to treatment, the possibility of this disease should be considered. If the patient exhibits symptoms of carcinoid syndrome, such as tachycardia, hypotension, asthma, dyspnea, abdominal pain, and diarrhea, along with skin flushing, the diagnosis is further supported.

For patients suspected of having carcinoid syndrome, laboratory tests such as preliminary screening tests, measurement of 5-HIAA in urine, and determination of 5-HT in tumor tissue can be performed. Imaging techniques like ultrasound, CT, MRI, and ERCP can be used for localization to provide diagnostic information for surgical planning.

bubble_chart Treatment Measures

1. Surgical Treatment

Similar to other functional endocrine tumors, early tumor resection is the preferred treatment for this disease; the surgical principles and choice of procedures remain the same. However, even if metastasis has occurred, symptoms can be alleviated or even eliminated by removing the primary carcinoid lesion. For multicentric or metastatic carcinoids unsuitable for radical resection, palliative pancreatic or hepatic lobectomy may also provide some therapeutic benefit.

2. Medical Treatment

(1) Avoid or minimize the use of drugs that promote 5-HT release, such as morphine, halothane, dextran, and polymyxin. Additionally, factors that may trigger carcinoid syndrome, such as alcohol consumption, emotional stress, and strenuous exercise, should be avoided or reduced.

(2) Use histamine 1 and histamine 2 antagonists to inhibit the secretion of histamine and peptide hormones by carcinoids. ① Methysergide: Used for treating carcinoid syndrome episodes. Administer 1–4 mg intravenously as a single dose, or infuse 10–20 mg in 100–200 ml of normal saline over 1–2 hours to control symptoms such as skin flushing, asthma, and diarrhea. ② Cyproheptadine: Take 4–8 mg orally, 3–4 times daily, to alleviate symptoms and achieve palliative effects.

(3) Tryptophan hydroxylase inhibitors: These drugs inhibit the activity of tryptophan hydroxylase, thereby reducing 5-HT synthesis and alleviating symptoms. ① Parachlorophenylalanine: Take 1 g orally, 3–4 times daily, to reduce or mitigate episodes of nausea, vomiting, diarrhea, and skin flushing. Side effects may include central nervous system dysfunction or hypothermia. ② Methylodpa: Used for pancreatic carcinoids secreting 5-hydroxytryptophan. Take 0.25–0.5 g orally, 4 times daily.

(4) Somatostatin: Broadly inhibits the release of endocrine hormones. In patients with pancreatic islet cell carcinoids, it can suppress pentagastrin-stimulated flushing.

(5) Chemotherapy: The use of chemotherapeutic agents such as 5-Fu and cyclophosphamide may alleviate symptoms, but the efficacy is relatively poor.