The incidence of intestinal metastasis with clinical evidence of lung cancer is only 0.2%-0.5%. In contrast, the incidence of primary lung cancer with intestinal metastasis has been reported in autopsy studies to be about 0.2%-14% (12, 13). Analysis of these studies has suggested that the incidence of primary lung cancer with intestinal metastasis is clinically not very low. The most common site of metastasis is the small intestine, with isolated cases of large intestine and anus also reported (14). Since lung cancer progresses to intestinal metastasis without apparent symptoms, most cases are detected by examination to exclude common site metastasis (15). It is found that a small percentage of intestinal obstruction is due to intestinal metastasis (16). Generally, the diagnosis of primary lung cancer with intestinal metastasis is late, and the incidence is low (13, 17). There is no unified standard for selecting clinical features and treatment methods for such cases. The overall clinical incidence rate was low, and there was no mature treatment experience for primary lung cancer with intestinal metastasis.
Most patients with intestinal metastasis of primary lung cancer will present with ileus or acute abdomen and require surgical intervention (18). Individualized treatment may improve the survival rate for these patients. Some studies showed no difference in the PFS between the patients who received adjuvant chemotherapy and those who received adjuvant chemo-radiotherapy (7). Our study suggested that patients who underwent surgical resection of the primary lesion or chemotherapy could improve their OS, which was inconsistent with previous studies. The literature reports that the most common metastatic sites of lung cancer were bone (34%), brain (28%), adrenal gland (17%), liver (13%), and other tissues, but intestinal metastasis was rare (19). The intestinal metastasis of primary lung cancer is insidious and lacks specific clinical symptoms, most of which are asymptomatic (20). The most common site of primary lung cancer with intestinal metastasis is the small intestine, and the lesions are primarily located in the ileum and jejunum, followed by the duodenum (14). The data in this study suggest that three-fifths of patients have small intestine metastasis, and nearly two-fifths have extensive intestine metastasis, which is consistent with previous studies.
The symptoms of intestinal metastasis mainly include acute intestinal obstruction, intestinal perforation, and even acute abdominal diseases such as intestinal bleeding and peritonitis (21). A Conventional endoscopic examination cannot explore the lesion site, but abdominal CT is helpful to identify the lesion (22). Therefore, for lung cancer patients with small bowel obstruction, intestinal metastasis should be highly vigilant, and abdominal CT should be perfected to evaluate the disease as far as possible. They should consider abdominal CT findings of local intestinal wall thickening, intestinal polyps, and surrounding lymph node lesions for intestinal metastasis(23). It has been reported that lung squamous cell carcinoma, large cell carcinoma, and multitype cell carcinoma are prone to intestinal metastasis. Some studies and autopsy data also show that lung adenocarcinoma is more prone to digestive tract metastasis (7). Our data tips pathological subtype of patients with intestinal metastasis of lung cancer are -- small cell carcinoma, poorly differentiated squamous cell carcinoma, poorly differentiated adenosquamous carcinoma, high-medium differentiated adenocarcinoma, invasive adenocarcinoma, moderate to poorly differentiated adenocarcinoma, poorly differentiated adenocarcinoma. The primary pathological type was adenocarcinoma, especially poorly differentiated adenocarcinoma; this is inconsistent with previous studies.
The relationship between histologic classification of lung cancer and susceptibility to intestinal metastasis is unclear. TTF-1, CDX-2, CK7, and CK20 Immunohistochemistry helps identify cancer cells’ tissue origin. Primary lung adenocarcinoma was positive for TTF-1, NapsinA, CK7, CK8, CK18 (24–26). Primary lung squamous cell carcinoma was positive for P40, P63, and CK5/6(26). Primary bowel cancer was positive for CK20 and CDX-2 but negative for CK7 and TTF-1(27). Our results are CK7 in all testing in patients with positive; CK, TTF − 1, NapsinA positive and CK20, CDX-2 negative in most patients. The pathological types and molecular marks of intestinal metastasis were consistent with lung primary lesions.
Most patients with intestinal metastases of primary lung cancer have no specific clinical manifestations, only showing positive fecal occult blood test, and a small number of patients present with intestinal symptoms such as abdominal pain, diarrhea, and hemifacial, while some patients present with acute abdominal symptoms such as acute intestinal obstruction and perforation (28). Most of the patients with intestinal metastases of primary lung cancer but without intestinal symptoms were detected by PET/CT whole-body scan. Therefore, for lung cancer patients, we should improve, especially those with distant metastasis to the liver, bone, and brain, fecal occult blood tests, and enhanced abdominal CT to guard against digestive tract metastasis (29). When not explained by the primary disease symptoms such as abdominal pain, diarrhea, or blood, we should think of the possibility of transferring the digestive tract. In recent years, there have been more and more reports of systemic PET/CT scans finding intestinal metastasis. For lung cancer patients without intestinal symptoms, the value of PET/CT in early detection of intestinal metastasis can be seen (30). In the routine diagnosis and treatment process of lung cancer patients, more and more doctors and patients choose PET/CT examination, but its clinical application is far from enough. PET/CT can detect intestinal metastasis, avoid missed diagnosis rates of CT scans and invasive endoscopy, and it's non-invasive. Semi-quantitative parameters of PET/CT can provide metabolic information on lesions. It can be used to understand the patient's condition, to help select treatment options and to assess prognosis. PET/CT examination can improve the efficacy and prognosis of patients with intestinal metastasis of lung cancer. Due to the limited data, this study could not explain the relationship between the semi-quantitative parameters of PET/CT and prognosis. However, our study showed that the SUVmax of intestinal metastasis was higher than primary lung lesions, which improved our understanding of the diagnosis of primary lung cancer with intestinal metastasis.
Systemic therapy (systemic chemotherapy, radiotherapy, targeted therapy, monoclonal antibody therapy) is the first choice for primary lung cancer with intestinal metastasis (31). If intestinal metastasis causes bleeding, obstruction, perforation, and other complications, emergency surgical treatment or immediate treatment is preferred (32). Our data suggest pneumonectomy, chemotherapy, and anti-PD-1 therapy improve patient outcomes. For patients who cannot tolerate surgical treatment, they can adopt other methods to relieve symptoms as much as possible.
Due to the continuous improvement of early diagnosis of tumors, the incidence of primary lung cancer with intestinal metastasis is increasing (33). However, there are few clinical cases and no complete diagnosis and treatment guidelines. The use of PET/CT in tumor patients provides strong evidence for screening and timely detection of primary lung cancer with intestinal metastasis. Previous studies have shown that the time interval between the diagnosis of primary lung cancer and intestinal metastasis is between 2 weeks and 4 years, it should improve the follow-up during the treatment process. Combined with the experience of advanced lung cancer treatment for comprehensive and individual treatment. The early detection of intestinal metastasis will contribute to timely treatment and improve the prognosis. Therefore, PET/CT can improve the diagnosis rate of primary lung cancer with intestinal metastasis, timely treatment, and avoiding the occurrence of intestinal obstruction can improve the prognosis of patients.