Apical lymphadenectomy during low ligation of the IMA during rectosigmoid resection for cancer.

BACKGROUND: Low ligation of the inferior mesenteric artery with preservation of the left colic artery may decrease the risk of colorectal anastomotic ischemia compared to high ligation at its origin. Low ligation leaves apical nodes in situ and is therefore paired with apical lymphadenectomy. We sought to compare relevant oncologic outcomes between high ligation and low ligation plus apical lymphadenectomy in rectosigmoid resection for colorectal cancer. METHODS: We conducted a retrospective cohort study. Patients receiving a rectosigmoid resection for cancer between January 2012 and July 2018 were included. Patients with metastatic disease and those who underwent low ligation without apical lymphadenectomy were excluded. Our primary outcome was nodal yield/metastasis. Secondary outcomes included perioperative complications, local recurrence, and overall survival. RESULTS: Eighty-four patients underwent high ligation and 89 low ligation plus apical lymphadenectomy (median follow-up 20 months). In the low-ligation group, a median of 2 (interquartile range = 1-3) apical nodes was resected; 4.1% were malignant, increasing pathologic stage in 25% of these patients. There were no differences in nodal yield, complications, anastomotic leak, local recurrence, or overall survival. CONCLUSION: No differences were identified between high ligation and low ligation plus apical lymphadenectomy with respect to relevant clinical outcomes. Prospective trial data are needed to robustly establish the oncologic benefit and safety of the low ligation plus apical lymphadenectomy technique.

Adequacy of lymph node harvest following colectomy for obstructed and nonobstructed colon cancer.

BACKGROUND: Technical and clinical differences in resection of obstructed and non-obstructed colon cancers may result in differences in lymph node retrieval. The objective of this study is to compare the lymph node harvest following resection of obstructed and nonobstructed colon cancer patients. METHODS: A retrospective analysis utilizing the 2014-2018 NSQIP colectomy targeted data set was conducted. One-to-one coarsened exact matching (CEM) was utilized between patients undergoing resection for obstructed and non-obstructed colon cancer. The primary outcome was the adequacy of lymph node retrieval (LNR, ≥12 nodes). RESULTS: CEM resulted in 9412 patients. Patients with obstructed tumors were more likely to have inadequate LNR (13.3% vs 8.2%, p < .001) compared to those with nonobstructed tumors. Multivariate analysis demonstrated that patients with obstructing tumors had worse LNR compared to non-obstructed tumors (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.62-0.87; p < .005). Increased age (OR: 0.99, 95% CI: 0.098-0.99), presence of preoperative sepsis (OR: 0.70, 95% CI: 0.055-0.90), left-sided and sigmoid tumors compared to right-sided (OR: 0.64, 95% CI: 0.51-0.81; OR: 0.69, 95% CI: 0.58-0.82, respectively), and open surgical resection compared to an minimally invasive surgical approach were associated with inadequate LNR (p < .05). CONCLUSION: This study demonstrated that resection for obstructing colon cancer compared to non-obstructed colon cancer is associated with increased odds of inadequate lymph node harvest.

Association of high ligation versus low ligation of the inferior mesenteric artery on anastomotic leak, postoperative complications, and mortality after minimally invasive surgery for distal sigmoid and rectal cancer.

BACKGROUND: In the treatment of distal sigmoid and rectal cancer, the appropriate level for the ligation of the inferior mesenteric artery (IMA) remains unresolved. High ligation divides the IMA proximally at its origin, and low ligation ligates the IMA distal to the origin of left colic artery. We assessed the association of level of ligation in scheduled minimally invasive resection of sigmoid and rectal cancers on anastomotic leak, postoperative complications, and death within 30 days. METHODS: We identified all patients with primary sigmoid and rectal cancer treated with scheduled minimally invasive resection and primary anastomosis between January 2002 and June 2018 using linked institutional and National Surgical Quality Improvement Program databases. We assessed the association of level of ligation with each outcome by fitting individual univariable and multivariable logistic regression models, adjusting for surgical approach, tumor location, neoadjuvant chemoradiotherapy, and Charlson comorbidity index. RESULTS: We included 158 patients treated with high ligation and 123 patients treated with low ligation. Overall, 12 patients had an anastomotic leak requiring intervention within 30 days: 5 in the high ligation group (3.2%, 95% CI 1.4-7.2%) and 7 in the low ligation group (5.7%, 95% CI 2.8-11.3%). There was no association between the level of ligation and anastomotic leak (unadjusted OR 1.85, 95% CI 0.58-6.38; adjusted OR 0.63, 95% CI 0.16-2.55). Similarly, there was no association between the level of ligation and reoperation for anastomotic leak (OR 1.29, 95% CI 0.15-10.9), major complications (Clavien-Dindo III-V; OR 2.22, 95% CI 0.90-5.77), minor complications (Clavien-Dindo I-II; OR 1.51, 95% CI 0.88-2.60), and all complications (OR 1.58, 95% CI 0.94-2.67). No deaths occurred in either group. CONCLUSIONS: There was no association of level of ligation of the IMA with anastomotic leak, postoperative complications as a composite, or death. The choice of high or low ligation of the IMA should be made based on technical factors such as length for the creation of a tension-free anastomosis.

Benefits of minimally-invasive surgery for sigmoid and rectal cancer in older adults compared with younger adults: Do older adults have the most to gain?

INTRODUCTION: Randomized trials demonstrated oncologic safety and short-term benefits of laparoscopy. We investigated if the benefit of laparoscopy on short-term outcomes is greater for older adults compared with younger adults. METHODS: We identified all older (≥70 years old) and younger (<70) adults with primary sigmoid and rectal cancer treated with resection between 2002 and 2018 from an institutional database. We compared 30-day postoperative outcomes using multivariable logistic regression with an interaction term between age group and surgical approach. Primary outcomes were death, major (Clavien-Dindo III-IV) and minor (Clavien-Dindo I-II) complications, and wound complications. RESULTS: We included 792 patients, 293 (37%) older and 499 (63%) younger. Use of laparoscopy was similar between age groups: 120/293 (41%) older, 204/499 (41%) younger (p = .98). All patients had 30-day follow-up. Compared with open resection, minimally-invasive resection was associated with a greater reduction in deaths in older adults than in younger adults (absolute difference in older adults 7.0% less versus 2.1% less in younger adults; adjusted odds ratio [aOR] older 3.01, 95% confidence interval [CI] 1.31-7.33; aOR younger 0.31, 95% CI 0.05-1.24; interaction p = .01). Similarly, minimally-invasive resection was associated with a greater reduction in major complications in older adults than in younger adults (absolute difference in older adults 6.4% less versus 2.4% less in younger adults; aOR older 1.91, 95% CI 1.07-3.41; aOR younger 0.70, 95% CI 0.34-1.38; interaction p = .03). CONCLUSIONS: Minimally-invasive compared with open surgery demonstrated a differential benefit on postoperative death and major complications between younger and older adults.

Microvascular Hepatic Artery Anastomosis in Pediatric Living Donor Liver Transplantation: 73 Consecutive Cases Performed by a Single Surgeon.

BACKGROUND: Living donor liver transplantation is an important strategy of procuring segmental liver allografts for pediatric patients with liver failure, as suitably sized whole donor organs are scarce. The early pediatric living donor liver transplantation experience was associated with high rates of hepatic artery thrombosis, graft loss, and mortality. Collaboration with microsurgeons for hepatic artery anastomosis in pediatric living donor liver transplantation has decreased rates of arterial complications; however, reported outcomes are limited. METHODS: A 14-year retrospective review was undertaken of children at the authors' institution who underwent living donor liver transplantation with hepatic artery anastomosis performed by a single microsurgeon using an operating microscope. Data were collected on demographics, cause of liver failure, graft donor, vessel caliber, vessel anastomosis, arterial complications, and long-term follow-up. RESULTS: Seventy-three children with end-stage liver failure underwent living donor liver transplantation with microvascular hepatic artery anastomosis. The commonest cause for liver failure was biliary atresia (63 percent). A total of 83 end-to-end hepatic artery anastomoses were completed using an operating microscope. Hepatic artery complications occurred in five patients, consisting of three cases of kinked anastomoses that were revised without complications and two cases of hepatic artery thrombosis (3 percent), of which one resulted in graft loss and patient death. Patient survival was 94 percent at 1 year and 90 percent at 5 years. CONCLUSIONS: Microvascular hepatic artery anastomosis in pediatric patients undergoing living donor liver transplantation is associated with a low hepatic artery complication rate and excellent long-term liver graft function. Collaboration between microsurgeons and transplant surgeons can significantly reduce technical complications and improve patient outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance.

Glycogen synthesis is a major component of the insulin response, and defective glycogen synthesis is a major portion of insulin resistance. Insulin regulates glycogen synthase (GS) through incompletely defined pathways that activate the enzyme through dephosphorylation and, more potently, allosteric activation. We identify Epm2aip1 as a GS-associated protein. We show that the absence of Epm2aip1 in mice impairs allosteric activation of GS by glucose 6-phosphate, decreases hepatic glycogen synthesis, increases liver fat, causes hepatic insulin resistance, and protects against age-related obesity. Our work identifies a novel GS-associated GS activity-modulating component of insulin resistance.

Glycogen hyperphosphorylation underlies lafora body formation.

OBJECTIVE: Glycogen, the largest cytosolic macromolecule, acquires solubility, essential to its function, through extreme branching. Lafora bodies are aggregates of polyglucosan, a long, linear, poorly branched, and insoluble form of glycogen. Lafora bodies occupy vast numbers of neuronal dendrites and perikarya in Lafora disease in time-dependent fashion, leading to intractable and fatal progressive myoclonus epilepsy. Lafora disease is caused by deficiency of either the laforin glycogen phosphatase or the malin E3 ubiquitin ligase. The 2 leading hypotheses of Lafora body formation are: (1) increased glycogen synthase activity extends glycogen strands too rapidly to allow adequate branching, resulting in polyglucosans; and (2) increased glycogen phosphate leads to glycogen conformational change, unfolding, precipitation, and conversion to polyglucosan. Recently, it was shown that in the laforin phosphatase-deficient form of Lafora disease, there is no increase in glycogen synthase, but there is a dramatic increase in glycogen phosphate, with subsequent conversion of glycogen to polyglucosan. Here, we determine whether Lafora bodies in the malin ubiquitin ligase-deficient form of the disease are due to increased glycogen synthase or increased glycogen phosphate. METHODS: We generated malin-deficient mice and tested the 2 hypotheses. RESULTS: Malin-deficient mice precisely replicate the pathology of Lafora disease with Lafora body formation in skeletal muscle, liver, and brain, and in the latter in the pathognomonic perikaryal and dendritic locations. Glycogen synthase quantity and activity are unchanged. There is a highly significant increase in glycogen phosphate. INTERPRETATION: We identify a single common modification, glycogen hyperphosphorylation, as the root cause of Lafora body pathogenesis.