The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities
On February 29, 2012, a 51-year-old woman presented to the emergency room for an initial workup of acute left lower quadrant pain. She was otherwise asymptomatic with a negative physical exam for pelvic mass or lymphadenopathy. The patient was in relatively good health prior to the development of her symptoms, reporting mild chronic complaints of gastritis and gastroesophageal reflux disease that had not been thoroughly evaluated or treated. Her prior surgical history included bilateral tubal ligation and cesarean section. The initial CT scan revealed retroperitoneal and mesenteric lymphadenopathy with a mass to the left of the uterine fundus. The subsequent ultrasound on March 12, 2012 showed two hypoechoic masses thought to be leiomyomata with normal-appearing adnexa. A follow-up PET/CT scan on March 14, 2012 was positive for two pathologically hypermetabolic pelvic masses and extensive hypermetabolic lymphadenopathy above and below the diaphragm. The subsequent lymph node biopsy on March 3, 2012 confirmed the presence of metastatic high-grade papillary serous ovarian carcinoma. Chemotherapy with carboplatin/paclitaxel was planned. However, following subclavian port-a-cath insertion, a localized infection developed that was treated with antibiotics, delaying the initiation of chemotherapy.\nShortly after diagnosis, the patient's initial laboratory evaluation (please refer to table for all laboratory reference ranges) showed a vitamin D deficiency of 16.7 ng/ml and a slightly elevated CRP of 3.65 mg/l. Her carcinoembryonic antigen was within the normal range at 1.8 ng/ml, and her cancer antigen (CA)-125 was elevated at 147 U/ml. She was given oral vitamin D3 at 50,000 international units per day by a nutritionist she saw independently. Her subsequent blood test 3 weeks later showed an elevated 25(OH)vitamin D level of 102.0 ng/ml with CRP continuing to increase to 5.27 mg/l.\nThe patient was seen at Amitabha Medical Clinic (Santa Rosa, Calif., USA) for a consultation on May 1, 2012, 2 months after her initial workup. She was interested in an integrative program to support her during the upcoming course of chemotherapy. Extensive laboratory workup was initiated. The results revealed a climbing CA-125 of 233.0 U/ml, a spike in CRP to 18.31 mg/l, and a highly elevated 25(OH)vitamin D level of 184.8 ng/ml. Helicobacter pylori IgM, IgG and IgA levels were elevated at >8.0 U/ml, with elevated IgA antibodies (Abs) at 2.35 U/ml. Fibrinogen activity and vascular endothelial growth factor (VEGF) were at the upper end of the normal range at 421 mg/dl and 690 pg/ml, respectively. The patient's galectin-3 level was 21.8 ng/ml. In recent research, the average value for galectin-3 in the general population was found to be 11.7 ng/ml []. In patients with congestive heart failure, abnormal levels for the galectin-3 ELISA test measure >17.8 ng/ml.\nA comprehensive integrative program was initiated to address the inflammation and treat the patient's comorbidities prior to beginning the course of chemotherapy. Treatments were also targeted to address the progressing cancer. The program included an intensive intravenous support protocol, an extensive oral nutrient and botanical regimen, dietary modifications including discontinuation of vitamin D3 supplementation, and other complementary therapies. The treatment of H. pylori was initiated with lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg administered together, po bid for 10 days. Intravenous therapies were performed twice per week in a progressively enhanced protocol. Oral supplementation focused on anti-inflammatory, antitumor, and immune-enhancing nutrients and botanical combinations. The patient's inflammatory status was improved with this approach, using multiple therapeutic modalities.\nLaboratory values 1 month after treatment initiation showed that galectin-3 decreased to 13.7 ng/ml, 25(OH)vitamin D to 120.0 ng/ml, and H. pylori IgA to 1.76 U/ml. The patient reported an improvement in her general condition and a reduction in pain and discomfort. Markers of cancer progression increased during the same period; CA-125 was 342.0 U/ml, VEGF was elevated at 876 pg/ml, and fibrinogen activity was above the normal range at 433 mg/dl. Chemotherapy was initiated on June 15, 2012 using standard protocols for carboplatin/paclitaxel along with a modified intravenous and oral complementary protocol. The CRP on July 4, 2012 showed a drop to the normal range at 2.29 mg/l. The patient had an excellent response to chemotherapy, with laboratory values of CA-125 reduced to 14.8 U/ml and galectin-3 reaching a low level of 11.9 ng/ml after 6 weeks of treatment.\nThe patient suddenly developed a widespread erythematous rash thought to be due to an allergic reaction to paclitaxel. This was later determined to be autoimmune dermatomyositis. CRP spiked to 14.31 mg/l, and treatment with cimetidine at 800 mg bid and betamethasone valerate topical cream, which was unsuccessful in resolving the rash, was initiated. Paclitaxel was discontinued. Oral prednisone at 20 mg, 3 tablets once per day, was prescribed as well as topical pimecrolimus 1% and fluocinonide 0.05% – with some improvement.\nA restaging CT scan (with oral and IV contrast) of the chest, abdomen, and pelvis on September 4, 2012 showed that the para-aortic and abdominal retroperitoneal lymph nodes were markedly reduced in size. No masses were visualized in the abdomen. The patient completed three more cycles of carboplatin only, with a total course of chemotherapy of 4.5 months. A post-treatment CT scan (with oral contrast) of the chest, abdomen, and pelvis on December 4, 2012 showed complete resolution of all masses without evidence of residual or recurrent metastatic disease. The CA-125 at this time was well within the normal range at 8.0 U/ml. However, galectin-3 was once again elevated at 24.3 ng/ml, with CRP elevated at 8.79 mg/l. The patient had continued on her dermatomyositis treatment regimen, but because of continuing symptoms, she was due to begin a more aggressive treatment with methotrexate 2.5 mg, 6 tablets once per week. Repeat galectin-3 on March 19, 2013 showed a highly elevated value at 48.3 ng/ml, with CA-125 remaining stable at 5.0 U/ml. A CT scan was planned to evaluate for cancer reoccurrence, which might not be reflected in serum tumor markers, along with initiation of methotrexate for dermatomyositis. Her CRP, CA-125 and galectin-3 levels will continue to be monitored as evaluation progresses.