Surgical indication and management of obstructive colonic metastasis from primary lung adenocarcinoma: report of a case and review of the literature

Background Colonic metastasis from lung cancer is very rare and is typically associated with poor prognosis. Herein, we report the case of a patient who achieved intermediate-term survival using a multimodal treatment approach, including chemotherapy, immunotherapy, radiotherapy, and surgical resection for obstructive colonic metastasis from primary lung adenocarcinoma. Case presentation A woman in her 50s presented with anemia and a positive fecal occult blood test. Computed tomography revealed a tumor in the right upper lobe of the lung with mediastinal lymphadenopathy and wall thickening in the transverse colon. Colonoscopy revealed a stricture involving 50% of the colonic lumen. Biopsy revealed a poorly differentiated adenocarcinoma positive for CK-7 and TTF-1, very focally positive for napsin A, and negative for CK-20 and CDX-2. Furthermore, positron emission tomography/CT (PET/CT) showed a high maximum standardized uptake value (SUVmax) of 8.2 in the iliac bone. Based on these findings, the patient was diagnosed with primary lung adenocarcinoma with simultaneous metastasis to the transverse colon and iliac bone (cT4N3M1c, cStage IVB). After receiving first-line chemotherapy with atezolizumab, pemetrexed, and carboplatin, the tumors shrank after 4 courses. Subsequently, the patient received maintenance therapy with atezolizumab and pemetrexed. However, the tumor enlarged after 10 courses. Second-line chemotherapy with docetaxel and ramucirumab (3 courses) failed to achieve tumor reduction. Colonoscopy revealed an impassable colonic tumor. Nineteen months after diagnosis, surgery was planned for imminent intestinal obstruction. We determined that the colonic tumor was resectable, because laparoscopic exploration revealed no other metastases. The tumor was resected by partial colectomy with ileocolonic anastomosis. The postoperative course was uneventful. Pathological examination revealed a resection margin that was negative for malignancy, and the histological type was consistent with metastatic lung adenocarcinoma. The patient then received nab-paclitaxel therapy; however, she developed symptoms of superior vena cava syndrome after 3 courses. The patient received palliative irradiation (30 Gy/10 fr) followed by nivolumab. She soon developed a solitary brain metastasis, and stereotactic irradiation was planned. After 3 courses of nivolumab, the metastasis was reduced significantly, and stereotactic brain irradiation was canceled. The lung tumor and mediastinal lymphadenopathy gradually shrank, and the patient survived for 13 months after surgery without disease progression. Conclusions In this case, surgical resection of colonic metastasis from primary lung adenocarcinoma may have contributed to the short-term prognosis as a bridge-to-next available multimodal treatment.


Background
The incidence and mortality rates of lung cancer have recently increased, particularly in developed countries compared to developing countries [1].Approximately 50% of patients with lung cancer present with extrapulmonary metastasis, most commonly in the bone, liver, and brain [2,3].Gastrointestinal metastases are often asymptomatic and difficult to diagnose before death.The actual incidence rate varies (0.5-10%) and depends primarily on the evaluation method [4].Colonic metastasis is a very rare type of gastrointestinal metastasis and is associated with a poorer prognosis compared to other gastrointestinal metastases [5].Herein, we report the case of a patient who achieved intermediate-term survival with multimodal treatment, including chemotherapy, immunotherapy, and radiotherapy, for primary lung adenocarcinoma and surgical resection for obstructive colonic metastasis.

Case presentation
A woman in her 50s presented with anemia and a positive fecal occult blood test.Chest computed tomography (CT) revealed an irregular mass exceeding 100 mm in diameter in the right upper lobe of the lung with mediastinal lymphadenopathy (Fig. 1a).Contrast-enhanced CT also revealed wall thickening in the transverse colon near the hepatic flexure (Fig. 1b).Colonoscopy revealed a tumor located approximately half circumferentially was reduced significantly, and stereotactic brain irradiation was canceled.The lung tumor and mediastinal lymphadenopathy gradually shrank, and the patient survived for 13 months after surgery without disease progression.in the hepatic flexure (Fig. 1c).Biopsy of the transverse colon tumor confirmed a poorly differentiated adenocarcinoma, which was positive for CK-7 and TTF-1, very focally positive for napsin A, but negative for CK-20 and CDX-2.Positron emission tomography/CT (PET/CT) revealed increased 18 F-fluorodeoxyglucose accumulation with maximum standardized uptake values (SUVmax) of 16.1 in the right upper lobe of the lung, 9.3 in the transverse colon, and 8.2 in the right iliac bone (Fig. 1d).
Based on these findings, the patient was diagnosed with right upper lobe lung adenocarcinoma with simultaneous metastases to the transverse colon and iliac bone (cT4N3M1c, cStage IVB).The primary lung tumor was considered surgically unresectable.Initially, no surgical intervention or endoscopic stenting was planned for the colonic metastasis because of the lack of stenotic symptoms.
The patient initially received first-line chemotherapy comprising atezolizumab, pemetrexed, and carboplatin (PEM + CBCDA).The primary tumor in the right upper lobe had shrunk to 66 mm by the end of 4 courses.Subsequently, the patient was administered maintenance therapy with atezolizumab and pemetrexed.However, follow-up CT scans revealed tumor growth in the lung and colon after the completion of 10 courses.The treatment regimen was then modified to second-line chemotherapy comprising docetaxel and ramucirumab, and the primary and metastatic tumors enlarged again after 3 courses.Although the patient did not have any stenotic symptoms, a subsequent colonoscopy identified a fully circumferential obstructing tumor in the transverse colon (Fig. 2).Nineteen months after the lung cancer diagnosis, surgical intervention was planned for the colonic metastasis, considering imminent intestinal obstruction.To minimize surgical complications, we allowed a drug-free period of 9 weeks before surgery.
Laparoscopic exploration revealed no peritoneal carcinomatosis or additional metastases beyond the colonic tumor.Further, the tumor demonstrated good mobility, suggesting no invasion of the surrounding organs, such as the pancreas or duodenum.Therefore, the tumor was intraoperatively determined to be completely resectable.Considering these factors and the tumor size, the laparoscopic approach was converted to open laparotomy for better access, and the wound was extended through a midline incision.The tumor was resected by partial colectomy with minimal lymph node dissection, and a 5-cm resection margin from the tumor was obtained.Furthermore, ileocolonic anastomosis was performed as a functional end-to-end anastomosis.The postoperative course was uneventful, and the patient was discharged 10 days after surgery.The macroscopic view of the resected specimen revealed an 80 × 60 mm, ulcerated, circumferential, and full-thickness tumor (Fig. 3a).The resection margins were negative for malignancy.Furthermore, the histological tumor type was moderately to poorly differentiated adenocarcinoma positive for CK-7 and TTF-1, very focally positive for napsin A, but negative for CK-20 and CDX-2 (Fig. 3b-f ).These findings were identical to those of the initial colonic biopsy diagnosis.
One month after surgery, the patient received nabpaclitaxel treatment.However, after 3 courses, she developed superior vena cava syndrome caused by a progressive lung tumor with mediastinal lymphadenopathy.Palliative irradiation therapy (at a dose of 30 Gy/10 fr) was then administered.Following irradiation, the patient received underwent immunotherapy with nivolumab.Soon after, a solitary brain metastasis was diagnosed (Fig. 4a), requiring stereotactic irradiation.After 3 courses of nivolumab, the brain metastasis was reduced significantly, and stereotactic irradiation was canceled.Additionally, the primary tumor and mediastinal lymphadenopathy gradually shrank (Fig. 4b).No recurrence of colonic metastasis was observed, and the iliac bone showed only sclerotic changes.The patient remained alive without disease progression at the end of 7 nivolumab courses (13 months after surgery).
Approximately 70.5% of gastrointestinal metastases from primary lung cancer involve multiple sites [5].Therefore, a thorough evaluation is necessary to identify any additional distant metastases before surgery for patients with gastrointestinal metastases.Even in cases with multiple small intestinal or colonic metastases, surgical resection may be indicated for localized lesions unless the surgery is overly invasive and requires multivisceral resection with complex gastrointestinal reconstruction.For patients who cannot tolerate radical surgery, stoma creation or endoscopic stenting may be considered as palliative options [28].In the present case, surgical intervention was undertaken to prevent intestinal obstruction, confirming tumor localization and resectability and preserving options for chemotherapy.Endoscopic colonic stenting or stoma creation offers a less invasive option.However, future therapeutic agents may include anti-vascular endothelial growth factors, such as bevacizumab or ramucirumab, which could increase the risk of perforation of the remaining tumor.Stoma creation can be easily performed and allows for prompt induction and continuation of the next treatment.However, in this case, the appropriate stoma site would have been the small intestine, which may have decreased tolerance to subsequent chemotherapy.The patient in the present study was judged tolerable to full surgical options because of the younger age and lack of significant comorbidities.The risks, benefits, advantages, and disadvantages of each interventional option were meticulously discussed, and the patient wished to undergo resection and anastomosis.After that, surgery was performed after obtaining a sufficient drug-free period.
Recent real-world data suggest that tyrosine kinase inhibitors and immune checkpoint inhibitors may improve overall survival in patients with non-small cell lung cancer [33].In the present case, the patient benefited from nivolumab therapy with good tumor control for primary lung cancer with mediastinal lymphadenopathy following complete resection of uncontrollable colonic metastasis.Therefore, local control of metastatic lesions is becoming increasingly important in lung cancer treatment.
This case report has some limitations.The diagnosis of primary lung cancer was based on radiological findings without cytology or biopsy results directly obtained from the lung tumor.In this case, the metastatic colonic tumor did not recur after surgical resection; however, the primary tumor had grown, and a new extrathoracic metastasis had occurred in the brain.Additionally, the molecular profiles and drug sensitivities may differ between primary and metastatic lesions.The literature review included only elective surgical cases that achieved reasonable survival times and did not include those that underwent emergency surgery with poorer survival, in whom surgery was inevitable and its indication was unquestionable.

Conclusions
In this case, surgical resection of colonic metastasis from primary lung adenocarcinoma may have contributed to the short-term prognosis as a bridge-to-next available multimodal treatment.

Fig. 1
Fig. 1 Imaging studies at the first diagnosis.a Chest computed tomography (CT) reveals a contrast-enhanced tumor exceeding 100 mm in diameter in the right upper lobe of the lung (traced with a dotted line) and adjacent mediastinal lymphadenopathy (arrowheads).b Abdominal CT reveals contrast-enhanced wall thickening in the transverse colon (arrowheads).c Colonoscopy shows an irregular, ulcerated, and raised lesion suggestive of an invasive tumor in the transverse colon.d Positron emission tomography/CT reveals increased 18 F-fluorodeoxyglucose accumulation in the right iliac crest (arrow)

Fig. 2
Fig. 2 Follow-up colonoscopy after the second-line chemotherapy.Colonoscopy reveals a circumferential, endoscopically impassable tumor in the transverse colon

Fig. 4
Fig. 4 Follow-up imaging studies after surgery.a Brain MRI with FLAIR/T2WI (fluid attenuated inversion recovery/T2-weighted image) shows solitary metastasis in the right frontal lobe (arrow).b Chest computed tomography shows shrinkage of the primary lung tumor and mediastinal lymphadenopathy with an ill-defined boundary (arrowheads)

M
male, F female, Scc squamous cell carcinoma, Adeno adenocarcinoma, Pleo pleomorphic carcinoma, U unknown * Survival time after diagnosis of gastrointestinal metastases ** Survival time after surgery for gastrointestinal metastases

Table 1
Summary of previously reported patients with colorectal metastases from primary lung cancer