"Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it is the only thing that ever has."

Margaret Mead

Case report
peer-reviewed

Small Bowel Perforation Due to Rare Metastasis From Stage IV Lung Adenocarcinoma



Abstract

Lung adenocarcinoma commonly metastasizes to the lymph nodes, bone, nervous system, liver, respiratory system, and adrenal gland. Metastasis to the small bowel is extremely rare and the literature deals mostly with few published case reports. We present a case of a 70-year-old male with a previous history of stage IV lung adenocarcinoma with brain and liver metastases treated with radiotherapy and chemotherapy. He presented to the emergency department with peritonitis and sepsis due to bowel perforation. He underwent an emergency exploratory laparotomy and small bowel resection. Surgical pathology revealed metastatic lung adenocarcinoma as the cause of bowel perforation. He tolerated and recovered from surgery well and was discharged on postoperative day 7. On one-month follow-up as an outpatient, he was doing well and had no complications or complaints from his recent surgery.

Introduction

The number one cause of cancer mortality within the United States is lung cancer [1]. Given that cancer can present itself at more advanced stages, physicians must know both common sites of metastasis as well as less common sites. The most common sites for lung cancer are lymph nodes (48%), liver (45%), adrenal gland (41%), bone (31%), and brain (25%) with a less common occurrence being the gastrointestinal tract (GI) (11.9%) [2,3]. Reports have previously shown that the small bowel is the most frequently noted gastrointestinal site of metastasis (10.67%) [2,3] with many cases presenting with either obstruction or perforation [4]. While there are case reports describing similar scenarios in the literature [5,6], the incidence of small bowel metastasis from lung cancer remains low [7]. Yet, it is important that physicians caring for patients with metastatic lung cancer presenting with acute peritonitis or abdominal symptoms keep a possible GI metastasis in their differential.

We report a case of a man with late-stage lung adenocarcinoma presenting with clinical and para-clinical symptoms of acute peritonitis secondary to perforation from a metastatic lesion. We also provide a brief review of case reports and retrospective chart review findings to provide insight into the case presented.

Case Presentation

A 70-year-old male with a past medical history of hypertension and hyperlipidemia was diagnosed two months ago with Stage IV Lung Adenocarcinoma of the right upper lung lobe metastatic to the brain and liver, after a witnessed fall incident. He had finished 1 course of cranial radiotherapy for a solitary brain mass, and one cycle of systemic chemotherapy, a week before he presented to the emergency department (ED) with progressively worsening, diffuse abdominal pain over two days. He did not report any significant abdominal symptoms or changes in bowel movements prior to the current onset. The workup in the ED included a complete blood cell count showing a WBC count of 28×103/µL and platelet count of 252x103/µL, and computed tomography (CT) chest/abdomen which revealed free peritoneal air with an interloop abscess at the distal jejunum concerning for perforation (Figures 1A-1C). The decision was made to perform an emergent exploratory laparotomy rather than a laparoscopy due to signs of acute peritonitis. During the operation, a small bowel perforation measuring approximately 0.5 cm at the level of distal jejunum-proximal ileum with interloop juxta mural abscess was identified concerning metastasis. Intraoperative findings corresponded to an ulcerated tumor mass involving most of the bowel circumference and measuring 3 cm x 3.5 cm. Approximately 30 cm of small bowel 15 cm proximal and 15 cm distal to the perforation site was resected and sent to pathology as a permanent specimen, along with portions of the mesentery with grossly enlarged lymph nodes. The continuity of the GI tract was reinstituted with a side-to-side functional end-to-end anastomosis and the mesenteric defect was closed. The small intestine was run from the ligament of Treitz to the ileocecal valve twice and no further pathologies were identified. The peritoneal cavity lavage with warm normal saline was performed. The patient tolerated the procedure well, was extubated, and was sent to the PACU in stable condition. The patient’s postoperative course was complicated by paroxysmal atrial fibrillation that was managed by Cardiology. Otherwise, his recovery from surgery progressed as expected and the patient was discharged on day 7 post-operatively with plans to continue systemic chemotherapy as recommended by his oncologist. The pathology report of the small bowel resection revealed metastatic adenocarcinoma involving 9/9 lymph nodes and negative margins. Immunohistochemistry (IHC) revealed that the mass was CK7 and TTF-1 positive, confirming a diagnosis of metastasis from lung adenocarcinoma (Figures 2A-2F). The patient was seen for outpatient follow-up after one month and doing well with no complications or complaints related to the operation. He plans to continue with systemic chemotherapy.

Discussion

Non-small cell lung cancer is more common than small cell lung cancer and comes in three main types, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, with advanced cases presenting with metastasis to the brain, lymph nodes, adrenals, or bone but rarely to the gastrointestinal tract [2]. However, it is questionable as to whether the scarcity of GI metastasis from lung cancer is due to it being undiagnosed in asymptomatic presentations versus presentations of acute peritonitis [6]. There still remain cases of GI metastasis in the literature [5,6] and thus it is key for physicians caring for patients with lung cancer to be aware of abdominal symptoms that may be significant for a metastatic lesion. To assess our case compared to current literature, we performed a Medline/Pubmed search for “small bowel metastasis” or “gastrointestinal metastasis” and “pulmonary carcinoma” for literature reviews on gastrointestinal metastasis of lung cancer, utilizing reference sections to search for additional reviews as needed. The results and details of the literature reviews can be found in Table 1

Author Year Country Chart Review or Lit Review Number of patients with lung cancer Number with GI mets Clinical Symptoms (n) Surgery (n) Type of Lung Cancer (n) Site of Metastasis for those with GI mets (n) Associated with other metastatic sites Patient survival after surgery
McNeil [2] 1987 USA Chart Review 431 46 Perforation (14/15) Obstruction (1/15) Laparotomy Squamous Cell (32.6%) Adenocarcinoma (28.3%) Small Cell (13.0%) Large Cell (26.1%) Small Bowel (46/431) 4.8 sites average Lymph nodes, adrenal gland, liver, kidney All <4 months
Berger, A [8] 1999 France Chart Review 1544 7 Acute peritonitis (2) Obstruction (3) GI Bleeding (2) Intestinal Resection (6) Bypass (1) Squamous Cell (3) Large cell (2) Adenosquamous (1) Adenocarcinoma (1) Jejunum (29%) Ileum (43%) Both (28%) Unspecified 8 months (6) Alive (1)
Garwood, R [5] 2004 USA Literature Review 98 98 Perforation (98)   Adenocarcinoma (23.7%) Squamous Cell (22.7%) Large Cell (20.6%) Small Cell (19.6%) Jejunum (53%) Ileum (28%) Both (4%) No specific site (13%) Unspecified 66 days mean survival 30 days (50%) >1 year (2%)
Yoshimoto, A [3] 2006 Japan Chart Review 470 56 Of those presenting with life threatening metastasis (n=12): Perforation (33%) Appendicitis (17%) GI Bleeding (33%) Ileus (17%) Intussusception (8%) Unspecified Adenocarcinoma (44.6%) Large Cell (21.4%) Small Cell (17.9%) Squamous (14.3%) Adenosquamous (1.8%) Small Intestine (68%) Gastric (43%) Large Intestine (38%) Multiple (52%) Yes, Liver, Adrenal, Kidney, Abdominal lymph node Unspecified
Goh, B [9] 2007 Singapore Chart Review 9 9 Obstruction (22%) Hemorrhage (33%) Intussusception (33%) Perforation (11%) Small bowel resection with primary anastamosis (55%) Subtotal gastrectomy with extended right hemicolectomy (11%) Gastrojejunostomy (11%) Right hemicolectomy (11%) Ulcerectomy (11%) Squamous Cell (33%) Large Cell (33%) Adenocarcinoma (11%) Pleomorphic (11%) Pleomorphic with adenocarcinoma (11%) Ileum (33%) Jejunum (33%) Cecum (11%) Duodenum (22%) Stomach (22%) Yes, brain, liver 89% discharged with median survival 6 months 50% >6 months 1 Alive
Po-Chu, Lee  [4] 2011 Taiwan Chart Review 8159 21 Perforation (14%) Hemorrhage (52%) Illeus (9.5%) Obstruction (14%) Abdominal Pain (14%) Tenesmus (9.5%) Segmental Resection (24%) Right Hemicolectomy (14%) Wedge resection of stomach (4.7%) Proximal Gastrectomy (4.7%) Adenocarcinoma (57%) Squamous Cell (24%) Pleomorphic (4.7%) Small Cell (4.7%) Undifferentiated (4.7%) Adenosquamous (4.7%) Small Bowel (29%) Stomach (38%) Duodenum (14%) Colon (14%) Multiple (9.5%) Yes, brain, bone, liver, adrenal gland, gall bladder, panceas, peritoneal seeding, ovary, uterus 1-3 months (62%) < 1 month (19%) >3 months (19%)
Jian-Zhong, D [6] 2014 China Literature Review 100 100 Perforation (46%) Obstruction (35%) GI Bleeding (14%) Exploratory laparotomy with resection and end-to-end anastamosis Large Cell (32%) Squamous Cell (27%) Adenocarcinoma (23%) Adenosquamous (3%) Carcinosarcoma (2%) Only small bowel metastases included Yes (70%) Brain, adrenal gland, bone, liver Median 2.3 months
Taira, N [7] 2017 Japan Chart Review 2066 7 Perforation (2) Gastric Bleeding (2) Intussusception (1) Acute Appendicitis (1) Colonoscopy (1) Emergency Laparotomy (4) Gastroendoscopy (2) Colonoscopy (1) Adenocarcinoma (4) Large Cell (1) Pleomorphic (2) Small Bowel (3) Gastric (2) Large bowel (1) Appendix (1) Brain (2) Bone (2) Skin (1) Adrenal (1) 6 months (1) 4 months (1) 5 months (1) 2 months (1) 3 months (1) 21 days (1)

The case presented was elucidated by a combination of imaging along with clinical and para-clinical symptoms whereby the finding of interloop jejunal abscess with progressive abdominal pain and free peritoneal air was suspicious for metastasis and perforation gave the patient’s history of multiple metastases to the brain and liver from lung adenocarcinoma. A review of the literature found that the median time between lung cancer diagnosis and GI metastasis is three months [4], which fits within the timeframe of our patient’s presentation. Our diagnosis was confirmed with exploratory laparotomy, which was necessary given the evidence for perforation, yet a CT abdomen done one month prior to this event during initial staging had not revealed metastasis to the small bowel. The use of CT imaging is adequate to confirm perforation or abscess in the setting of an acute abdomen though it is difficult to distinguish small metastatic lesions within the small bowel [10], and PET/CT, which can theoretically show increased uptake to metabolically active lesions, have not shown to demonstrate a diagnostic advantage over CT alone [11]. IHC for the specimen showed CK7 and TTF-1 positively which is in line with Lung Adenocarcinoma, which has been shown in several studies to be the leading type of lung cancer in small bowel metastases [3-5,7]; however, other studies may indicate that either squamous cell carcinoma [2,8,9] or large cell carcinoma [6,9] is more likely. This is further supported by TTF-1 having been shown to appear in 89% of metastatic lung adenocarcinoma cases and CK7 having been shown to appear in all cases of lung cancer [11]. One report indicated that large cell carcinoma has an overall 3.5 times greater rate of gastrointestinal metastasis and accounted for 30% of those metastases [6].

Without evidence of perforation, it may have been vastly difficult to be able to diagnose metastasis in the patient described. Perforation itself is a poor prognostic indicator in the realm of intestinal metastasis with lung cancer [6]. While our patient underwent a round of chemotherapy a few days prior to presentation at our hospital, there is inconsistent data to show an increased incidence of perforation, though a majority (75.5%) received either single or combined therapy 2 days to 4 years prior to a perforating event [5]. In similar situations, it has been found that aggressive surgical intervention can provide effective palliation for lung cancer patients with acute abdomen secondary to gastrointestinal metastasis, though in that study all those who survived more than 6 months did not have extrapulmonary spread outside of the gastrointestinal tract [9], unlike our patient presenting with both brain and liver metastases. Several different reviews suggest that perforation may be a leading presentation for pulmonary metastasis to the small bowel as compared to obstruction, intussusception, or gastrointestinal bleeding [3,4,6], though other reviews show a more mixed incidence of presentations [7-9].

Other reviews indicated that all small bowel and colon metastases required surgery to relieve either obstruction or perforation [3,4]. In addition to our case, this highlights the importance of being able to identify small bowel metastasis prior to the onset of acute abdomen. Possible approaches include video capsule endoscopy (VCE) which has been shown to be able to diagnose small bowel tumors in places not easily reachable by traditional endoscopic methods, along with regular colonoscopies for colon metastases [12,13]. Our patient had a colonoscopy with non-significant findings two years prior to his cancer diagnosis, and a CT abdomen one month prior to the perforation event, which may indicate that such screening tests may not be well equipped to diagnose metastasis from lung cancer.

Overall, previous reviews have been mixed on what the most common gastrointestinal site is for lung cancer metastasis with leading sites being the jejunum and ileum, followed by the duodenum and the cecum. The exploratory laparotomy in this case found the perforation and metastasis at the proximal ileum-distal jejunum given that it manifested as a loop abscess, making the exact location difficult to define.

Our patient had a post-operative course complicated with paroxysmal atrial fibrillation but otherwise was able to be discharged on postoperative day 7 and found to be doing well on a one-month outpatient follow-up. Survival means post-surgical intervention, in one report was six months, though those patients were specifically selected and did not have any other extrapulmonary metastasis [11]. The literature is mixed in survival rates, with some noting median rates of 2.3 months or a greater majority of patients surviving until one to three months [4,6].

Conclusions

To summarize, our case is one of a number of reports of lung cancer spreading to the small bowel, resulting in perforation and subsequent necessitation for exploratory laparotomy. This adds to the growing literature on this occurrence and could indicate that the prevalence of such metastasis may be higher than expected with most only being ascertained at the point of perforation. Data might also need to be collected on whether chemotherapy treatment on patients with lung cancer and unknown GI metastasis may allow for risk factors that induce a perforating event.


References

  1. CDC wonder on-line database, compiled from compressed mortality file 1999-2016 series 20 no. 2v, 2017. National Center For Health Statistics. (2017). Accessed: November 19, 2018: https://wonder.cdc.gov/cmf-icd10.html.
  2. McNeill PM, Wagman LD, Neifeld JP: Small bowel metastases from primary carcinoma of the lung. Cancer. 1987, 59:8-1486. 10.1002/1097-0142(19870415)59:8<1486::aid-cncr2820590815>3.0.co;2-w
  3. Yoshimoto A, Kasahara K, Kawashima A: Gastrointestinal metastases from primary lung cancer. Eur J Cancer. 2006, 42:3157-60. 10.1016/j.ejca.2006.08.030
  4. Lee PC, Lo C, Lin MT, Liang JT, Lin BR: Role of surgical intervention in managing gastrointestinal metastases from lung cancer. World J Gastroenterol. 2011, 17:4314-20. 10.3748/wjg.v17.i38.4314
  5. Garwood RA, Sawyer MD, Ledesma EJ, Foley E, Claridge JA: A case and review of bowel perforation secondary to metastatic lung cancer. Am Surgeon. 2005, 71:110-6. 10.1177/000313480507100204
  6. Di JZ, Peng JY, Wang ZG: Prevalence, clinicopathological characteristics, treatment, and prognosis of intestinal metastasis of primary lung cancer: a comprehensive review. Surg Oncol. 2014, 23:72-80. 10.1016/j.suronc.2014.02.004
  7. Taira N, Kawabata T, Gabe A, et al.: Analysis of gastrointestinal metastasis of primary lung cancer: clinical characteristics and prognosis. Oncol Lett. 2017, 14:2399-404. 10.3892/ol.2017.6382
  8. Berger A, Cellier C, Daniel C, et al.: Small bowel metastases from primary carcinoma of the lung: Clinical findings and outcome. Am J Gastroenterol. 1999, 94:1884-7. 10.1111/j.1572-0241.1999.01224.x
  9. Goh BK, Yeo AW, Koong HN, Ooi LL, Wong WK: Laparotomy for acute complications of gastrointestinal metastases from lung cancer: is it a worthwhile or futile effort?. Surg Today. 2007, 37:370-4. 10.1007/s00595-006-3419-y
  10. Bhutta SI, Ahmed Y, Zahid T, Rehman HU, Nur MM, Mahmood T, Calvert P: Colonic metastasis of primary lung cancer. Case Rep Oncol. 2021, 14:901-5. 10.1159/000516795
  11. Alkabie S, Bello B, Martinez RF, Geis WP, Ballo MS: Metastatic adenocarcinoma of unknown origin presenting as small bowel perforation: A case report and literature review. J Investig Med High Impact Case Rep. 2015, 3:2324709615577415. 10.1177/2324709615577415
  12. Cheung DY, Kim JS, Shim KN, Choi MG: The usefulness of capsule endoscopy for small bowel tumors. Clin Endosc. 2016, 49:21-5. 10.5946/ce.2016.49.1.21
  13. Badipatla KR, Yadavalli N, Vakde T, Niazi M, Patel HK: Lung cancer metastasis to the gastrointestinal system: an enigmatic occurrence. World J Gastrointest Oncol. 2017, 9:129-34. 10.4251/wjgo.v9.i3.129

Case report
peer-reviewed

Small Bowel Perforation Due to Rare Metastasis From Stage IV Lung Adenocarcinoma


Author Information

Francesco Sautto Corresponding Author

Surgery, University of Central Florida College of Medicine, Orlando, USA

Sarah Tinsley

Pathology, University of Central Florida (UCF) HCA Lake Nona Hospital, Orlando, USA

Vladimir Neychev

Surgery, University of Central Florida College of Medicine, Orlando, USA


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.



Case report
peer-reviewed

Small Bowel Perforation Due to Rare Metastasis From Stage IV Lung Adenocarcinoma


Figures etc.

SIQ
7.8
RATED BY 5 READERS
CONTRIBUTE RATING

Scholarly Impact Quotient™ (SIQ™) is our unique post-publication peer review rating process. Learn more here.