A Case of Tumor Lysis Syndrome Induced by Surgery in Colon Cancer with Multiple Liver Metastases

Abbreviations:

TLS-Tumor Lysis Syndrome; CEA- Carcinoembryonic Antigen; DIC-Disseminated Intravascular Coagulation

1. Introduction

Tumor lysis syndrome (TLS) is a well described oncologic emergency. The syndrome is deemed spontaneous when it occurs before initiation of any cytotoxic or definitive treatment. Here, we report the rare case of a 70-year old man with colon cancer and extensive liver involvement manifesting with TLS following surgery. Previous investigators had demonstrated only fourteen cases with TLS associated in colorectal cancer [1-14]. Ten of the fourteen cases were induced by chemotherapy, three were spontaneous tumor lysis syndrome (STLS), and one was induced by radiofrequency ablation (RFA). This is therefore the first report of TLS induced by surgery in case of colon cancer with liver metastases.

2. Case Presentation

A 70-year old Japanese man, who had been in good health until two months prior to this admission, presented with worsening abdominal pain, accompanied by loss of appetite, fever and subjective weight loss. The patient also complained of postprandial abdominal pain in the right upper quadrant. Blood examination revealed anemia and elevated levels of the tumor marker, carcinoembryonic antigen (CEA). His past medical history detailed two previous abdominal operations, due to intestinal obstruction fifty years ago. His social history was negative for tobacco use, alcohol use and use of illicit drugs.

Physical examination revealed right upper quadrant tenderness on deep palpation with no signs of peritonitis, and bilateral pitting edema up to the knees. Cardiovascular, pulmonary, and neurological examinations were grossly normal. Laboratory findings at the time of presentation included: white blood cells: 9.35 × 10³/μL, hemoglobin: 7.7 g/dL, platelets: 353 × 10³/μL, potassium: 4.5 mmol/L, serum creatinine: 0.77 mg/dL, albumin: 2.9 g/dL, total bilirubin: 0.7 mg/dL, alanine aminotransferase: 1037 U/L, aspartate aminotransferase: 40 U/L, alkaline phosphatase: 47 U/L and lactate dehydrogenase levels: 979 U/L. Elevated CEA was observed at 283.6 ng/UL. Colonoscopy revealed a mass in the transverse colon: biopsy of the mass confirmed a moderately- to well-differentiated invasive adenocarcinoma (Figure 1). Computed tomography scan of the abdomen and pelvis revealed hepatomegaly with multiple liver lesions alongside with mural thickening of the transverse colon, with ascites across the whole body (Figure 2). The patient underwent right hemicolectomy as the palliative surgery to prevent anemia or colon obstruction. On the first postoperative day, the patient experienced tumor lysis, with lactate dehydrogenase levels: 20072 U/L, uric acid: 8.7 mg/dL, serum potassium: 6.8 mEq/dL, serum calcium: 7.4 mg/dl, and serum phosphate: 6.3 mg/dL (Table 1). Kidneys ultrasound showed normal renal parenchyma with no evidence of obstructive uropathy. We diagnosed this as TLS. All available supportive measures, including continuous hemodiafiltration, were initiated from 1 to 7 postoperative days. Then, the patient also experienced liver failure and disseminated intravascular coagulation (DIC) from 3 to 11 postoperative days (Table 1). The patient subsequently recovered from TLS, and was administered the anticancer-drugs (FOLFOX) on postoperative day 21.

Figure 1: Colonoscopy showing a Bormann II type tumor at the transverse colon (arrow).

Figure 2: Computed tomography scan revealing multiple liver metastasis and ascites across the whole peritoneal cavity. The arrow represents the tumor at the transverse colon.

POD: postoperative day; DIC: disseminated intravascular coagulation

Table 1: Laboratory trends in the patient presented.

3. Discussion

We present here the first case of TLS as a complication after surgery for metastatic colon adenocarcinoma. TLS is an oncological emergency precipitated by massive release into the circulation of intracellular tumor contents, manifesting in distinct laboratory abnormalities including hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. While TLS is most commonly observed in hematological cancers, it can also be seen in solid malignancies with large tumor burdens [15]. These include breast cancer, small cell lung cancer, germ cell tumor, melanoma, Merkel cell carcinoma, head and neck cancer, non-small cell lung cancer, ovarian cancer, vulva cancer, prostate cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, sarcoma, neuroblastoma, medulloblastoma, hepatoblastoma, gestational trophoblastic neoplasia, renal cell carcinoma, transitional cell carcinoma, and thymoma [6].

In most patients, TLS occurs as a result of chemotherapy, however, it may also be induced by other anti-neoplastic treatments, including radiotherapy, hormone therapy and immunotherapy, or may develop spontaneously before initiation of therapy [16, 17]. STLS is defined as the TLS occurring in the absence of any definitive treatment [18]. The incidence of STLS in solid tumor is rare. The first step for TLS diagnosis is based on the laboratory findings in an appropriate clinical context. Hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia are the primary indicators of TLS [15, 16]. Clinical TLS is considered when traditional laboratory findings are accompanied by diarrhea, nausea, vomiting, lethargy, cardiac arrhythmias, seizures, or sudden death [17, 18]. Patient care when TLS has been established should include astute monitoring of uric acid, potassium, phosphorous, calcium, lactate dehydrogenase and serum creatinine levels, alongside cardiac monitoring and monitoring urine output. Allopurinol may be a useful prophylactic to lower uric acid production in patients at risk of TLS. However, allopurinol use may result in elevated xanthine levels by inhibiting xanthine oxidase in patients with TLS [19-21]. Xanthine may also precipitate in the renal tubules, contributing to obstructive uropathy in a similar manner as uric acid [20, 21]. As a result, rasburicase, which converts uric acid to soluble allantoin, is the recommended drug for hyperuricemia in TLS [15, 16, 18, 19]. The dialysis need to be initiated for hyperkalemia, hyperphosphatemia, or hypocalcemia [15]. The present case was not treated with rasburicase, due to a sufficient decrease in uric acid by the second postoperative day through continuous hemodiafiltration.

The first reported case of TLS in a nonhematological malignancy occurred in 1977 [22]. Approximately 120-140 reported cases of tumor lysis in solid tumors have since been reported, mostly after treatment, between 1977 and 2018 [6, 19]. Although there was different origins of primary tumors, extensive liver involvement has been noted in 82.8% of all cases. When the liver was not involved, patients inevitably had a large tumor burdens accompanied by necrosis. As noted by Gemici et al. [16], liver involvement seems to predispose patients to the TLS. This may be due to a high purine pool in the liver, which may be released during necrosis, or due to impaired uric acid metabolism if hepatic function is impaired by a high tumor burden [16]. TLS in solid tumors is unpredictable and carries a worse prognosis when compared to hematological malignancies [16]. Mortality rates are 20%–50% across all cases of TLS in solid tumors if undiagnosed or if diagnosed too late [19, 23].

Our literature review of TLS in patients with colon cancer revealed only three cases of STLS, ten of tumor lysis induced by a chemotherapy, one of tumor lysis induced by RFA, and the present case of tumor lysis induced by surgery [1-14] (Table 2). This case may represent a pre-process to STLS during surgery, though it is difficult to understand why TLS was induced by surgery. Of the fifteen cases, including the present case identified, most cases had multiple liver metastasis, with larger tumor volumes, and only five (33.3%) recovered from TLS. Early diagnosis and treatment are crucial if patients are to survive TLS.

STLS, spontaneous tumor lysis syndrome; RFA, radiofrequency ablation;

FOLFIRI, 5-fluorouracil, leucovorin and irinotecan; FOLFOX: 5-fluorouracil, leucovorin and oxaliplatin.

Table 2: Fifteen cases induced tumor lysis syndrome in colorectal cancers.

In conclusion, we reported the first documented case of TLS induced by surgery in a colon cancer with multiple liver metastases. This patient recovered from TLS by early diagnosis and treatment, including continuous hemodiafiltration due to resolve hyperuricemia and hyperkalemia.

Conflict of Interest

The authors declared that they have no competing interests.

Consent for Publication

The informed consent for publication and presentation was obtained from the patient.

Funding

This work was no supported from any funding.

Authors’ Contribution

MY drafted the manuscript. NI, HY, YT, AS, and HK acquired data and revised the manuscript. All authors have read and approved the final manuscript.

Acknowledgments

We thank Dr. Masafumi Ohya for pathological diagnosis.

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