High lipid, low dextrose parenteral nutrition allows patient to achieve nutritional autonomy: A case report.

INTRODUCTION: Prolonged use of parenteral nutrition can eventually lead to liver abnormalities. Causative factors include decreased enteral stimulation, high intakes of intravenous dextrose, proinflammatory 100 % soybean oil-based lipids, and increased burden on liver through 24-h infusions. We present a case report of a patient who received parenteral nutrition modifications to address liver dysfunction. PRESENTATION OF CASE: Our patient was a 37-year-old African American male with a past medical history including refractory Crohn's disease complicated by multiple small bowel obstructions, several bowel surgeries, left lower quadrant colostomy placement, short bowel syndrome, severe protein calorie malnutrition, parenteral nutrition dependence, and elevated liver function tests. He was admitted for nutritional optimization before a planned takedown of multiple chronic enterocutaneous and perianal fistulas. His home parenteral nutrition order contained high amounts of dextrose (69 % kcal), and low amounts of 100 % soybean oil (11 % kcal). DISCUSSION: Due to an elevated alkaline phosphatase level at baseline (1746 U/L), the Registered Dietitian maximized protein, decreased the dextrose by 62.5 %, and changed to SMOFlipid (a fish-oil containing lipid) at >1 g/kg/day to address liver abnormalities. Within 1.5 months of changing parenteral nutrition to high SMOFlipid (>30 % kcal) with low dextrose (<30 % kcal) content, alkaline phosphatase levels declined by 62 %, prealbumin levels increased by 56 %, and c-reactive protein levels decreased by 62 %. CONCLUSION: Parenteral nutrition modifications led to reversal of chronic liver dysfunction. This patient ultimately underwent a successful high-risk fistula takedown procedure, allowing for complete weaning of parenteral nutrition and achievement of sustained nutritional autonomy.

Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate post-operative period: a Phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis.

Aim: Evaluate safety/efficacy of intravenous meloxicam in a colorectal enhanced recovery after surgery protocol. Methods: Adults undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis received meloxicam IV 30 mg (n = 27) or placebo (n = 28) once daily beginning 30 min before surgery. Results: Adverse events: meloxicam IV, 85%; placebo, 93%. Adverse events commonly associated with opioids: 41 versus 61% - including nausea (33 vs 50%), vomiting (19 vs 18%) and ileus (4 vs 18%). Wound healing satisfaction scores (physician-rated), clinical laboratory findings and vital signs were similar in both groups. No anastomotic leaks were reported. Opioid consumption, postoperative pain intensity, length of stay and times to first bowel sound, first flatus and first bowel movement were significantly lower with meloxicam IV versus placebo. Most subjects (>92%) were satisfied with postoperative pain medication. Conclusion: Meloxicam IV was generally well tolerated and associated with decreased opioid consumption, lower resource utilization and functional benefits. Clinical Trial Registration: NCT03323385 (ClinicalTrials.gov).

Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

BACKGROUND: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. METHODS: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. RESULTS: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4-80.6] and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. CONCLUSIONS: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. IMPACT: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.

CD 133+ and CXCR4+ colon cancer cells as a marker for lymph node metastasis.

INTRODUCTION: Colorectal cancer (CRC) stem cells or tumor-initiating cells (Co-TIC) are implicated in both cancer recurrence and extranodal metastasis. CD133 and CXCR4 are specific cell surface markers that are indicators of Co-TIC. The presence of lymph node (LN) metastases is one of the strongest negative prognostic factors for CRC patients. We examined the relationship between the Co-TIC markers CD133 and CXCR4 and LN involvement in CRC. METHODS: CRC cells were isolated via enzymatic digestion. CD133(+), CXCR4(+), and double-positive CRC cells were detected by fluorescence-activated cell sorting analysis. The percentages of CD133(+), CXCR4(+), and double-positive cells were identified and correlated to the number and percentage of positive LN on staging. RESULTS: Twenty-seven samples underwent fluorescence-activated cell sorting analysis. The mean percentage of CD133(+) cells was 3.94% (range 0.15%-19.06%). The mean percentage of CXCR4(+) cells was 6.15% (range 0%-27.11%). The mean percentage of CD133(+)CXCR4(+) cells was 0.45% (range 0%-2.08%). Thirteen patients had LN metastasis: 8 N1 disease and 5 N2 disease. The correlation coefficients between the percentage of Co-TIC marker-positive cells and percentage of positive LN were r = 0.58 (P = 0.0016) for CD133(+) cells, r = 0.36 (P = 0.5868) for CXCR4(+) cells, and r = 0.56 (P = 0.0022) for double-positive cells. DISCUSSION: Our results show CD133(+) and CD133(+)CXCR4(+) cancer cells correlate with the presence of LN metastasis in CRC. Further studies will examine whether these markers can give consistent prognostic information and may help to develop novel diagnostic and therapeutic options.

History and pathogenesis of lynch syndrome.

Lynch syndrome is the familial clustering of colorectal and endometrial cancers. This syndrome is passed in an autosomal dominant fashion within families with defective mismatch repair as the genetic basis for cancer development in these patients. There remains a group of patients who fit clinical diagnostic criteria for an autosomal dominant familial cancer syndrome, which is phenotypically similar to Lynch syndrome, but for which no mismatch repair mutation is identified. Identification of alternate genetic mutations such as EPCAM and CHEK2 may explain the cancer risk in a small subset of these patients, but continuing work into the genetic basis of colorectal familial cancer syndromes is needed.

Lymph node stromal cells enhance drug-resistant colon cancer cell tumor formation through SDF-1α/CXCR4 paracrine signaling.

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths in America. Nearly two thirds of newly diagnosed CRC cases include lymph node (LN) involvement, and LN metastasis is one of the strongest negative prognostic factors for CRC. It is thought that CRC tumors contain a small population of drug-resistant CRC tumor-initiating cells (Co-TICs) that may be responsible for cancer recurrence. To evaluate the effects of the LN stromal cells on Co-TICs, we established a unique xenoplant model using CRC cells isolated by enzymatic digestion from consented patient specimens, HT-29 cells, HCA-7 cells, and LN stromal cell line HK cells. We found that HK cells and HK cell-conditioned media enhanced CRC tumor formation and tumor angiogenesis. Cells expressing CD133(+) and the stromal cell-derived factor 1α (SDF-1α) receptor CXCR4 were enriched in chemotherapeutic-resistant CRC cells. CD133(+)CXCR4(+) Co-TICs isolated from patient specimens are more tumorigenic than unsorted tumor cells. Furthermore, the inhibitors specific to HK cell-derived SDF-1α reduced tumor formation and tumor angiogenesis. Our results have demonstrated a role for Co-TICs in tumor growth and defined the influence of LN stromal cells on Co-TICs. We have identified a major Co-TIC/LN microenvironment-specific mechanism for CRC resistance to chemotherapeutic agents and established experimental platforms for both in vitro and in vivo testing, indicating that SDF-1α and its receptor, CXCR4, may be targets for clinical therapy.