Two cases of superior mesenteric artery syndrome during chemotherapy in patients with lung cancer

Abstract

Superior mesenteric artery (SMA) syndrome is a rare disease, characterized by the narrowing of the third portion of the duodenum between the aorta and SMA. The cause of the stenosis is a decrease in retroperitoneal fat between the aorta and SMA. In this report, we present two cases of SMA syndrome that occurred during chemotherapy for lung cancer. The first case was a 61-year-old male treated with nanoparticle albumin-bound-paclitaxel (nab-PTX) for lung adenocarcinoma. On day 23 of the first course of nab-PTX, he was admitted to our hospital due to vomiting and weight loss of 15.6 kg in 10 months. He was diagnosed with SMA syndrome through computed tomography, and drainage was performed using a nasogastric tube. Conservative treatment was successful, and the patient was able to continue therapy with nab-PTX. The second case was a 70-year-old male with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. He was admitted to our hospital due to vomiting and dizziness while receiving treatment with pembrolizumab, as well as weight loss of 14.6 kg in 6 months. He was diagnosed with SMA syndrome using computed tomography. Conservative treatment using a nasogastric tube led to improvement, and the patient was able to continue treatment with pembrolizumab after discharge. This is the first report of SMA syndrome in patients with lung cancer undergoing chemotherapy with nab-PTX or pembrolizumab. Late diagnosis and treatment render SMA syndrome a potentially fatal disease. Vomiting and weight loss during chemotherapy are known treatment-related side effects; in patients developing these adverse effects, the presence of SMA syndrome should be suspected and managed appropriately.

Introduction

Superior mesenteric artery (SMA) syndrome is a rare medical condition, in which the third portion of the duodenum is compressed between the aorta and SMA. This syndrome is attributed to a decrease in retroperitoneal fat [1]. The causes of retroperitoneal fat loss include multiple trauma, sepsis, anorexia nervosa, and burns [2]. Symptoms reflecting duodenal obstruction include upper abdominal pain after eating, nausea, vomiting, anorexia, and weight loss [1]. These symptoms may improve in the prone or left lateral position and worsen in the supine position [3]. The patients may eat even less due to these symptoms, resulting in additional weight loss [4]. The diagnosis of SMA syndrome is difficult due to its non-specific symptoms. Importantly, delayed diagnosis and inadequate treatment may render SMA syndrome a life-threatening condition [5]. Thus far, only two cases of SMA syndrome that developed during chemotherapy for lung cancer and malignant pleural mesothelioma have been reported. In the first case, a patient with lung cancer receiving cisplatin-based chemotherapy developed SMA syndrome [6]. In the second case, a patient with malignant pleural mesothelioma receiving carboplatin-based chemotherapy developed SMA syndrome [7]. In this article, we report two cases of SMA syndrome that occurred during chemotherapy with nanoparticle albumin-bound-paclitaxel (nab-PTX) or pembrolizumab for lung cancer.

Case report

Case 1

A 61-year-old Japanese male with lung adenocarcinoma (cT4N1M0 stage IIIA) was admitted to our hospital. Three years earlier, he had undergone radical surgery after chemoradiation and postoperative chemotherapy. Following disease recurrence with multiple lung metastases, he was treated with docetaxel, pemetrexed, and atezolizumab; however, the disease progressed. Therefore, nab-PTX was administered as fifth-line treatment. On day 23 of the first cycle of nab-PTX, he was urgently hospitalized due to severe vomiting. At the time of admission, the patient (height: 183.5 cm; weight: 52.7 kg; body mass index [BMI]: 15.7 kg/m²) reported weight loss of 15.6 kg in 10 months. Physical examination revealed a flat and soft abdomen, diminished bowel sounds, and no tenderness. Laboratory data revealed low albumin (3.1 g/dL) and high C-reactive protein (2.02 mg/dL) levels. Computed tomography (CT) showed that the duodenum was compressed between the aorta and SMA, and intestinal distension was observed in the oral side of the obstruction (Fig. 1). The distance and the angle between the aorta and SMA were 5 mm and 10°, respectively. Although we attempted to perform upper gastrointestinal endoscopy, severe vomiting did not allow us to complete this procedure. A nasogastric tube was inserted, and the patient was fasted with intravenous fluids. On day 7 after admission, the nasogastric tube was removed and food intake was initiated. He was discharged on day 13 and continued treatment with nab-PTX as an outpatient. Subsequently, the patient was able to continue therapy with two cycles of nab-PTX and two cycles of gemcitabine as sixth-line treatment. His body weight increased by 6.8 kg, to 59.5 kg (BMI: 17.7 kg/m²). However, recurrence of SMA syndrome was detected on day 12 of the second cycle of gemcitabine. A nasogastric tube was also inserted, and the patient improved with conservative treatment. The clinical course of case 1 is shown in figure (Fig. 2).

Fig. 1.

Contrast-enhanced computed tomography showing duodenal compression by the aorta (Ao) and superior mesenteric artery (SMA) and gastric dilatation. The distance between the aorta and SMA was 5 mm (a). The angle between the aorta and SMA was 10° (b)

Fig. 2.

Clinical time course of case 1

Case 2

A 70-year-old Japanese male with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (cT1bN3M0 stage IIIB) was admitted to our hospital; he had been diagnosed 1 year earlier. He was hospitalized due to vomiting and dizziness on day 21 of treatment with pembrolizumab, as second-line therapy after the administration of afatinib. The patient (height: 162.5 cm; weight: 45.4 kg; BMI: 17.2 kg/m²) had experienced weight loss of 14.6 kg in 6 months. Physical examination revealed a flat and soft abdomen, diminished bowel sounds, and no tenderness. Laboratory data revealed a high number of white blood cells (23,700/μL), renal dysfunction, low albumin (3.6 g/dL) levels, and high C-reactive protein (6.22 mg/dL) levels. CT showed that the duodenum was compressed between the aorta and SMA, and intestinal distension was observed in the oral side of the obstruction (Fig. 3). The distance and the angle between the aorta and SMA were 3 mm and 6°, respectively. The patient was diagnosed with SMA syndrome, and a nasogastric tube was inserted. On day 3 after admission, total parenteral nutrition was initiated. Upper gastrointestinal endoscopy showed a stenotic site that was thought to be extramural compression. Retention of contrast medium was observed in the third portion of the duodenum. Considering the possibility of immune-related colitis due to treatment with pembrolizumab, lower gastrointestinal endoscopy was performed; nevertheless, the findings were not suggestive of colitis. Subsequently, the symptoms improved, and the patient was discharged on day 27; of note, he continued to receive pembrolizumab as an outpatient. A total of six cycles of pembrolizumab were administered. One year following its initial onset, SMA syndrome recurred; however, conservative treatment led to improvement. The clinical course of case 2 is shown in figure (Fig. 4).

Fig. 3.

Computed tomography showing duodenal compression by the aorta (Ao) and superior mesenteric artery (SMA) and gastric dilatation. The distance between the aorta and SMA was 3 mm (a). The angle between the aorta and SMA was 6° (b)

Fig. 4.

Clinical time course of case 2

Discussion

Superior mesenteric artery syndrome, which is characterized by significant weight loss, is a noteworthy complication occurring in patients with cancer [6]. This syndrome was first reported by Rokitansky in 1842; however, Wilkie reported SMA syndrome in 1927, and his name has become a common eponym for this condition [1, 8]. According to upper gastrointestinal barium studies, the estimated prevalence of SMA syndrome is 0.013–0.3% [1].

Thus far, only two cases of SMA syndrome that occurred during chemotherapy have been reported. In the first case, a 61-year-old male with squamous cell carcinoma of the lung receiving cisplatin and docetaxel developed SMA syndrome with epigastric pain and vomiting on day 17 of the first treatment cycle. The patient experienced weight loss of 7 kg in 6 months. CT showed compression of the third portion of the duodenum; the aortomesenteric distance was 6.1 mm and the aortomesenteric angle decreased to 15.8°, resulting in the diagnosis of SMA syndrome. Drainage was performed with a nasogastric tube, and the patient recovered after conservative treatment [6]. In the second case, an 81-year-old male with malignant pleural mesothelioma receiving carboplatin and pemetrexed developed SMA syndrome with epigastric pain and severe vomiting. He experienced weight loss of 18 kg in 6 months. CT showed expansion of the stomach and the duodenum, compression of the third portion of the duodenum, and a decrease in the aortomesenteric angle to < 20°, leading to the diagnosis of SMA syndrome. Drainage was performed with a nasogastric tube, and the patient recovered after conservative treatment with total parenteral nutrition and intravenous fluids [7]. These two patients were receiving treatment with relatively highly emetogenic anti-cancer drugs. In contrast, the two patients discussed herein were treated with less emetogenic anti-cancer drugs, such as nab-PTX and pembrolizumab. It is noteworthy that SMA syndrome occurred during treatment with a single anti-cancer drug less emetogenic effects than platinum doublets. To the best of our knowledge, this is the first report of SMA syndrome development during treatment with nab-PTX or pembrolizumab in patients with lung cancer. All four patients (two previous and two present) had experienced prolonged weight loss for 6 months or more prior to the onset of SMA syndrome. This observation suggests that the side effects associated with chemotherapy and cancer-induced weight loss affect the onset of SMA syndrome [6, 7]. Neoplasms and systemic chemotherapy cause anorexia and weight loss, however, SMA syndrome is rare even in these patients. The etiology of SMA syndrome is still unclear. It has also been reported that 40.4% of SMA syndromes are idiopathic [9]. SMA syndrome is often caused by rapid and severe weight loss [10]. To the best of our knowledge, there is no literature how rapid and severe weight loss caused SMA syndrome. We presumed that rapid and severe weight loss, such as 15.6 kg weight loss in 10 months in case 1 and 14.6 kg weight loss in 6 months in case 2, might cause SMA syndrome in our cases. It has been reported that innate risk factors for the development of SMA syndrome are a low origin of SMA or a short Treitz ligament [8]. SMA syndrome occurs without weight loss in adolescence, because retroperitoneal fat is poorly developed as compared to height growth. There was no abnormality of the origin of SMA or the Treitz ligament in our two cases.

The diagnosis of SMA syndrome is often missed or delayed due to the non-specific symptoms of the condition. The differential diagnoses include motility disorders, gastroesophageal reflux disease, pancreatitis, peptic ulcer disease, biliary colic, and mesenteric ischemia [11]. The diagnosis of SMA syndrome is based on radiological findings. In healthy individuals, the distance and angle between the aorta and SMA are 10–28 mm and 25°–60°, respectively. However, in patients with SMA syndrome, these values are < 8 mm and < 22°, respectively [12–14]. For our two patients, the distances were 5 mm and 3 mm, and the angles were 10° and 6°, respectively. The treatment of SMA syndrome is followed by insertion of a nasogastric tube and follow-up in the prone or left lateral position [1, 15]. In the absence of improvement, surgery may be performed [10]. For such cases, duodenojejunostomy is the procedure of choice, while Strong's procedure may also be considered [16]. As far as we know, there is no literature for the prognosis of SMA syndrome in patients with advanced lung cancer during chemotherapy, because advanced lung cancer itself is more decisive in prognosis and SMA syndrome can improve with early diagnosis and appropriate treatment. Conservative treatment and nutritional therapy as same as initial treatment is usually performed when SMA syndrome recur. It is most important for the patients with SMA syndrome not to relapse.

Conservative treatment with nasogastric tubes led to improvement in both of our patients. In case 1, long-term cytotoxic chemotherapy and chemotherapy without intervals may have also contributed to the weight loss. Our patients experienced long-term weight loss due to lung cancer, and we suggest that chemotherapy triggered the SMA syndrome. For the prevention of SMA syndrome in patients with cancer, it is necessary to closely monitor their weight and nutritional status. Both of our patients had recurrent SMA syndrome, and their weight was poorly controlled. It is important to monitor weight changes during chemotherapy; in case of weight loss, appropriate nutritional support to the patients is required. Various methods, including the use of a nasogastric tube with nutritional support and parenteral nutrition, can be utilized to help patients gain weight [4].

In conclusion, we experienced two cases of SMA syndrome that occurred during chemotherapy with nab-PTX or pembrolizumab for lung cancer. In addition to the side effects linked to chemotherapy, SMA syndrome should be considered a potential cause of vomiting during chemotherapy in this setting.

Abbreviations

BMI

Body mass index

CT

Computed tomography

EGFR

Epidermal growth factor receptor

nab-PTX

Nanoparticle albumin-bound-paclitaxel

SMA

Superior mesenteric artery

Declarations

Conflict of interest

The authors report no conflicts of interest in this work.