An obese 64-year-old woman with insulin-required diabetes and a BMI of approximately 40, initially presented to her endocrinologist with elevated serum liver function tests — particularly the alkaline phosphatase, ALT — and ASP. Echogenic lesions are noted on ultrasound, and a CT scan revealed multiple lesions of metastatic disease. Subsequent abdomen and pelvic CT did not show any primary pancreatic lesions or other disease. Colonoscopy revealed a non-obstructing descending colon cancer and two polyps in the right colon. She participated in significant nutritional counseling, changed her fat intake and changed her caloric intake. She received 12 treatments of FOLFOX and bevacizumab. CT showed progression of liver metastases and serum CEA levels are found to be elevated. The primary colon tumor is still asymptomatic. She is switched to FOLFIRI and cetuximab, and her serum CEA dropped significantly after four months. Colonoscopy revealed marked response to liver lesions and no residual mucosal primary tumor.
Case Discussion:
DR CURLEY: This was an obese 64-year-old woman with insulin-dependent diabetes and a BMI of almost 40 who had initially presented to her endocrinologist with elevated serum liver function tests, particularly alkaline phosphatase, ALT and ASP. Echogenic lesions were noted on ultrasound, and a CT scan revealed multiple bilobar liver lesions suggestive of metastatic disease. Subsequent CT of the abdomen and pelvis did not show a pancreatic primary lesion or other disease. Colonoscopy revealed a nonobstructing mass in the descending colon and two polyps in the right colon. Her biopsy results showed adenocarcinoma of the sigmoid colon.
We planned to begin systemic treatment with chemotherapy, but because the patient was diabetic, we worried about diabetic neuropathy. She did have some loss of sensation already in both of her feet. She had also been counseled that we needed to be cautious with her dose of chemotherapy, because of her renal function. Her creatinine was borderline normal (~1.6), so we were concerned about her hydration status during chemotherapy. Parenthetically, we’ve also noted that for patients who receive chemotherapy, diabetes is also a predictor of developing both steatosis and steatohepatitis on chemotherapy. Irinotecan is known to cause steatohepatitis in some patients. If the patient is a diabetic, the risk of developing chemotherapy-induced steatohepatitis with irinotecan is even higher, so we are cautious about using irinotecan as a neoadjuvant prior to resection of the liver metastases in diabetic patients.
We were treating this patient with a curative intent so the preference was to use an oxaliplatin-based regimen for neoadjuvant therapy, recognizing that it may confound any preexisting diabetic neuropathy. Several ongoing studies are evaluating the role of diabetes in neuropathy-related oxaliplatin. Is the neuropathy worse? Does it develop after fewer cycles? These things have been suggested, but I’ve seen no definitive proof. We are watching the ongoing studies closely because we’d love to know if we should change our dose of oxaliplatin. Should you change the number of cycles of oxaliplatin, or should we treat these patients even more aggressively by using things like calcium/magnesium and other things that reduce the oxaliplatin-induced neuropathy?
We counseled her aggressively regarding diet and put her through some significant nutritional counseling, changed her fat intake and changed her caloric intake. Previously, she had not been doing a great job monitoring her diabetes. Interestingly enough, her liver function tests improved during chemotherapy probably because she improved her diet and was able to improve the management of her diabetes.
She had a good response to therapy in both her metastatic disease and in her primary tumor. I think the key teaching point is that bilobar disease does not mean incurable — it does not mean you don’t treat with curative intent. The key is whether or not you can resect the metastatic disease in the liver and leave an adequate volume of good functioning liver, well-profused liver and well-drained liver (ie, biliary drainage). For this patient, we deemed that that was possible, so we counseled her that a liver resection would be potentially possible.
We proceeded with that liver resection, and she tolerated that well and had excellent hypertrophy of her liver as a result. We have found that if diabetes is well controlled and is kept well controlled in the postoperative period, hepatic regeneration is normal and does not regenerate at a slower rate. These patients don’t have an increased incidence or risk of liver insufficiency or liver failure as long as we maintain their blood sugar in a good range. We like to keep their blood sugar under 180 while they’re in the regenerative period, and we find that these folks fare quite well. In fact, her recovery from the hepatic resection was uneventful.
