Successful Treatment of Recurrent Colonic Adenocarcinoma with Metastatic Tumor Thrombus in the Superior Mesenteric Vein with Surgical Excision and Venous Reconstruction

Background

Patients with Hodgkin’s lymphoma (HL) are known to be at increased risk of second malignancies. The risk of solid malignancies after treatment of HL, such as lung, colon, and breast cancer, has been studied extensively [1]. Colorectal cancer is reported to be the third most common solid malignancy in survivors of HL, and survivors are reported to have a 2.4-fold increased risk of developing colorectal cancer when compared with the general population [1].

Radiation-induced secondary malignancies are a known late adverse effect of radiation therapy [2]. Inverted Y-field radiation for patients with HL has been shown to have a 15.9-fold increased risk of transverse colon cancer [1]. Radiation therapy can cause significant injury of normal tissues in the radiation field, and the gastrointestinal tract is a particularly radiosensitive tissue, which can be a limiting factor in determining a patient’s potential tolerance of radiotherapy [3]. Despite the known increased risk of colon cancer in HL patients after radiation, radiation-associated colon cancer is reported to be a rare clinical entity [3].

Given the increased number of cancer survivors, post-radiation malignancies are of growing concern in the field of oncology [2]. We present a case of a patient with HL who, after radiation, developed colon cancer with subsequent metastasis to the superior mesenteric vein, a rare clinical entity of which similar presentation has not been known to be reported to date.

Case Report

The patient was a 56-year-old woman with a past medical history of stage III HL diagnosed at age 13, which was treated by splenectomy, 3 months of chemotherapy, and mantle and inverted Y radiation therapy. Thirty-eight years later, she developed a renal cell carcinoma, which was treated with right nephrectomy. Forty-three years after treatment for HL, she was found to have an 8-cm mass in the transverse colon. She underwent right colectomy for pathological stage IIA (T3N0M0) adenocarcinoma. No adjuvant therapy was administered, and she continued with active surveillance. A liver mass was identified about a year later, which was biopsied and found to be an adenoma. Later that year, another mass was identified, and was initially thought to represent a para-duodenal lymph node. The mass could not be biopsied safely percutaneously, and a biopsy was unable to be obtained with an endoscopic ultrasound. The mass was observed on short-term imaging, and was fluorodeoxyglucose (FDG) avid on positron emission tomography (PET) and showed restricted diffusion on magnetic resonance imaging (Figure 1). Contrast-enhanced computed tomography demonstrated a tumor in the superior mesenteric vein on the sagittal and the coronal planes (Figure 2). The mass slowly enlarged on 3 serial PET scans over a 6-month interval, no other metastases developed, and the patient was referred for consideration of resection. She underwent radical resection of the 3-cm tumor with porto-mesenteric reconstruction using an inter-positioned saphenous vein graft (Figure 3). The final pathology results revealed the mass was metastatic colonic adenocarcinoma with involvement of the superior mesenteric vein, with 1 of 7 lymph nodes positive for adenocarcinoma, and negative margins (Figure 4). The patient completed 12 cycles of adjuvant treatment with fluorouracil (5-FU), and no further metastases had been identified 5 years after her surgical excision of the metastatic tumor.

Discussion

HL AND SECONDARY COLON CANCER:

Colon cancer metastasis to a superior mesenteric vein is extremely rare, and we have not been able to find a similar case reported in the literature. In patients with HL, the reported relative risks range from 2 to 7, compared with that in the general population [4]. This increased risk can continue for up to 40 years after treatment of HL [4]. HL survivors who have been treated with either procarbazine and/or abdominal radiation have been noted to have a high prevalence of premalignant polyps [4]. The screening guidelines of the Children’s Oncology Group now recommend screening for colorectal cancer 5 years after radiation or at age 30 years (whichever occurs last) with a colonoscopy every 5 years or multitarget stool DNA test every 3 years [5]. In patients with HL, radiotherapy exposes healthy tissues to radiation [6]. More specifically, in patients who receive infra-diaphragmatic radiation, colon, rectal, and bladder cancer are reported to result as post-radiation secondary malignancies in patients with HL [6]. In the present case, the patient was treated with radiation as part of her HL therapy, which may have contributed to the development of her transverse colon cancer. The occurrence of the primary transverse colon cancer and the metastases in the inverted Y-field radiation implicates the late effects of radiation in her cancer.

COLON CANCER METASTASIS AND RADIATION:

Colorectal cancer metastases most commonly occur in the regional lymph nodes, liver, lungs, and peritoneal cavity, and less commonly in other sites [7]. In rectal cancer, large vessel venous invasion can be seen and is an adverse prognostic factor [8]. Proposed models of metastatic spread of malignancies includes the “seed-and-soil” hypothesis. This hypothesis originally proposed that metastasis occurs when there is the presence of a favorable environment for the growth of tumor cells with metastatic potential. Studies done during the last several decades have provided a better understanding of the mechanisms of metastatic spread of malignancies [9].

For example, the transforming growth factor a/epidermal growth factor receptor signaling pathway also plays a role in colon cancer metastasis [10]. Activation of the receptor and subsequent signaling pathway helps promote cell proliferation, migration, survival, and adhesion, ultimately promoting metastasis [10].

Radiotherapy cures the majority of early-stage HL but can cause long-term toxicity to the adjacent organs [11]. The cumulative 30-year risk of second malignancies after treatment for HL is 30% for men and 20% for women [12]. The risk of serious cardiovascular events is 30% for both men and women [12]. While metastasis to irradiated tissues is a relatively rare clinical event, radiation can directly and indirectly impact the microenvironment in a way that enhances invasion, migration, and metastasis [13]. In animal models, radiation of the lung or liver prior to primary tumor inoculation in a distant site led to and increased metastatic burden in the irradiated organ [13]. In general, in humans there is no propensity toward metastasis to irradiated tissues [13]. Radiation has rarely been reported to induce local pro-invasive effects in breast cancer, and in prostate and rectal cancer, radiotherapy can increase the activity of matrix metalloproteinases in the local microenvironment and tumor, which is thought to promote invasion [13].

GASTROINTESTINAL MALIGNANCIES IN HL:

Patients with HL who receive infra-diaphragmatic radiotherapy have a 5-fold higher risk of developing colorectal cancer, and these cancers are demonstrated to have a higher frequency of microsatellite instability due to somatic mutations in mismatch repair genes [14]. HL patients with gastrointestinal malignancies have long been reported to have worse overall and disease-specific survival than other patients with gastrointestinal malignancies, which has been postulated to be due at least in part to differences in carcinogenesis, such as being treatment-induced in HL patients [15]. However, recent advancements in treatment and the increase in the proportion of stage IV colorectal cancer in the last 25 years has created the space for improved survival [16]. This has been attributed in part to the improvement in detection of metastasis as well as to advancements in systemic therapy and surgical options for patients with metastatic disease [16]. Despite the advancements in treatment, though, HL survivors who develop a second malignancy are still reported to have a substantially lower life expectancy [17].

SURGICAL EXCISION OF COLORECTAL CANCER METASTASIS:

Surgical resection of metastases from colorectal cancer is the curative option in oligometastatic cancer. Colorectal cancer with metastasis to the liver and lung can be cured with resection [18,19]. Little information is available about surgical options for malignancies in the venous structures. Surgical options following portal trauma include selective portal ligation [20]. Patients with portal vein injury can also be treated with portal injury repair, which requires isolation, exposure, and repair of the vein in cases of trauma [21]. Surgical repair can include lateral venorrhaphy, interposition graft, end-to-end anastomosis, or portal-systemic shunting [21].

There are reported cases of tumor thrombosis in the superior mesenteric vein in patients with colorectal cancer that have been treated surgically [22–24]. The presence of superior mesenteric vein thrombosis is also a rare sequela of colorectal cancer, with reports suggesting an incidence of venous tumor thrombosis of 1.7% [22]. Surgical options for thrombosis to the superior mesenteric vein include hemicolectomy with thrombectomy and subsequent vein grafting, as well as laparoscopy-assisted colectomy for complete tumor resection followed by adjunctive chemotherapy, as tumor and thrombus removal is suggested to improve prognosis in these cases [22,23]. There is 1 case report of combined right hemicolectomy with resection of tumor thrombosis in the superior mesenteric vein and saphenous vein grafting. In the case of that patient, surgical excision of the primary tumor and the tumor thrombus in the superior mesenteric vein, with negative margins, followed by systemic chemotherapy with oxaliplatin and capecitabine resulted in a long-term remission [22].

Conclusions

Patients with a history of HL with radiation treatment may be at increased risk of not only solid malignancies but also solid organ malignancy metastasis to previously irradiated sites, including venous structures.