Unresectable Mesenteric Masses: Fact or Fiction J. Philip - PowerPoint PPT Presentation

“Unresectable” Mesenteric Masses: Fact or Fiction J. Philip Boudreaux, MD FACS Professor of Surgery LSUHSC – New Orleans Chairman, Department of Surgery Ochsner Medical Center - Kenner

Med edic ical v l vs S s Surgic ical M l Man anagement is t s the e wrong Questio ion • Medical management ultimately FAILS with either progression, complications, or death • The question we need to ask is: When is the optimal timing for surgical intervention and how can surgery make medical management more efficacious to prevent future complications and improve quantity and quality of life? • Medical management (including PRRT) should be viewed as complimentary to surgical care, not in place of it

Obstruction and Infarction

Who determines “Unresectability” in Your Institution? • The consequences of mesenteric encasement with bulky adenopathy and fibrosis are variable but can and often include intractable abdominal pain, intestinal ischemia, recurrent obstructions, malnutrition, and intestinal gangrene (1-4)

89 year old patient with Carcinoid Syndrome EXT 5 HIAA BLOOD 0 - 22 ng/ml 607 (A) EXT SEROTONIN 56 - 244 ng/ml 1,363 (A) EXT CHROMOGRANIN A 25 - 140 ng/ml 687 (A) EXT PANCREASTATIN ISI10 - 135 pg/ml 2,509 (A

89 year old patient, had medical therapy over 7 years, presents with worsening abdominal pain, episodic bloating, diarrhea, progressive weight loss, after increasing doses of SSRI to Q 2 weekly, Affinitor X 1 year, Capecitabine/Temazolamide x 1 year, and PRRT. Ar Are t e the s he symptoms s due t to: • Partial Intestinal Obstruction • Intestinal Ischemia • Pancreatic insufficiency • Poorly controlled syndrome • Chronic cholecystitis • All of the above

• Resect all Small Bowel Tumor(s)with “Adequate” Margins, Lymphatic Mapping minimize anastomotic recurrences • Conservation of Bowel Length • Mesenteric Lymphadenectomy • Restore/Spare Blood Supply • Spare Ileocecal Valve Whenever Possible based on Mapping

• 170 Patients for cyto-redructive operations • 49 patients under mapping • 27 patients with midgut primary • 15 patients with tumor near ileo-cecal valve • 88% resection margins modified • 40% ileo-cecal valve preserved • 0% anaphylactic reaction to isosulphan blue

Results Subset: Tumor Involving Mesenteric Root (n = 41) • 50% patients explored elsewhere and declared non-resectable • Symptoms of mesenteric ischemia and/or small bowel obstruction (SBO) • 39/41 (95%) were able to be resected • 37/41 (90%) with a marked improvement in symptoms • Median Survival > 200 months Lyons JM, Lindholm E, Wang YZ, Thomson JL, Lowell AB, Woltering EA, Frey DJ, Joseph S, Ramcharan T, Boudreaux JP . Extensive Retroperitoneal Carcinoid Involving the Mesenteric Vasculature Does Not Preclude Effective Cytoreduction. Pancreas . 2010;39(2):274-275 . doi:10.1097/01.mpa.0000363921.55478.e6 .

Journal of the American College of Surgeons 2017 224, 434-447DOI: (10.1016/j.jamcollsurg.2016.12.032)

250 Median Survival in Months 200 150 Months 100 50 0 Woltering-2013 Bergestuen-2009 Oberg-2008 Talamonti-2002 Ahmed-2009 SEER (1988-2004) SEER (1988-1999) SEER (1973-1987)

Survival (n=229 Well Diff Midgut) Stage IV 2006-2012 • Median survival from histologic diagnosis of a NET was 236 months • 56% had mesenteric encasements dissected • Kaplan-Meier survival rates • 5-year 87% • 10-year 77% • 20-year 41% • Nearly Twice the national average at all time points

Prophylactic Surgical Approach to Stage IV Small Bowel NETs, Daskalakis, et.al., Jama Oncol 2018 • “Prophylactic” (within 6 months of diagnosis) 161 patients vs 202 “wait and see” , operated for symptoms 1985-2005 • Showed no difference in median survival: 94.8 vs 91.2 months ( vs 236 mos in a more recent series 2006-12) • No data regarding how many had mesenteric encasement, only that when present in made “dissection challenging”

Mean Karnofsky Scores p < 0.0001 85 90 80 65 70 60 50 40 30 20 10 0 Pre - Op Post - Op

What about “selection bias”? • 50% unoperated, declared unresectable at time of referral • 30% explored elsewhere and closed, declared “unresectable” • 30% misdiagnosed as “poorly controlled syndrome” had partial intestinal obstruciton

Technical Aspects to Remember • An overly aggressive dissection at the mesenteric root can result in a vascular catastrophe, sacrificing critical collateral vessels, or putting the main superior mesenteric arterial and/or venous trunks at risk. • An asymptomatic calcified fibrotic mass encasing the mesenteric root should probably be left in place in inexperienced hands. • Specialized neuroendocrine centers have developed methods to surgically remove these nodal metastases at the root and have reported a lower incidence of obstruction, intestinal angina, and avoided mesenteric ischemia and intestinal gangrene (1-14)

Resect or not to resect? • Can the first jejunal branch of the SMV and SMA be preserved? • If not, do not operate or stop where you are. • Nutritional status? • Can something else be done besides resection of “unresectable” tumors intraoperatively? • Yes, IRE ( nanoknife ablation), argon beam (Plasmajet) vaporization and partial unroofing to decompress the vessels anteriorly in cases of intestinal ischemia, and IR stenting of the SMA and or SMV in selected cases, AND even Multivisceral Organ Transplantation (MVOT)

Things to consider: • Patients should not be denied the opportunity for surgical evaluation in a multidisciplinary tumor board to determine timing and sequencing of multimodal therapies including surgery. • “Not a surgical candidate” may mean “not right now” • Patients should be reevaluated over time as their disease progresses and new therapies/operations become available Complex liver resections, mesenteric dissections , and • transplantation are not prospective, randomized, nor controlled entities They are extreme examples of “operator dependent” outcomes •

Things to consider: • It has been well established for Ovarian cancer and Myxomatous tumors that peritoneal cytoreduction followed by chemotherapy prolongs survival and improves QOL. Why would we not apply similar principles to a slow growing malignancy ? • Should patients be subjected to increasing frequency of painful injections, systemic chemotherapy and radiation when an operation could suffice? • With the threat of a limited supply of healthcare dollars looming, would an operation be more economical than years of medical therapy that will ultimately require an operation but now perhaps with an increased risk of complications (and therefore cost) because the patient is now in extremis ?

Why is there a debate? • We can make as much tumor go away as we can in a few hours , then one can hold it at bay with whatever medical therapy one chooses • Surgery never gave anyone AML of myelodysplastic syndrome • Decisions need to be made as to where and when surgical options should be exercised by experienced centers in a multidisciplinary setting

89 y/o with abdominal pain, weight los, diarrhea, bloating. EXT 5 HIAA BLOOD 0 - 22 ng/ml 607 (A) EXT SEROTONIN 56 - 244 ng/ml 1,363 (A) EXT CHROMOGRANIN A 25 - 140 ng/ml 687 (A) EXT PANCREASTATIN ISI10 - 135 pg/ml 2,509 (A)

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Mesenteric Dissection • References • 1. Howe JR, Cardona K, Fraker DL, Kebebew E, Untch BR, Wang Y, et al. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society. Pancreas. 2017 July;46(6):715. • 2. Norlén O, Stålberg P, Öberg K, Eriksson J, Hedberg J, Hessman O, et al. Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg. 2012;36(6):1419-31. • 3. Landry CS, Lin HY, Phan A, Charnsangavej C, Abdalla EK, Aloia T, et al. Resection of at-risk mesenteric lymph nodes is associated with improved survival in patients with small bowel neuroendocrine tumors. World J Surg. 2013 July 01;37(7):1695-700. • 4. Landerholm K, Zar N, Andersson RE, Falkmer SE, Jarhult J. Survival and prognostic factors in patients with small bowel carcinoid tumour. Br J Surg. 2011;98(11):1617-24. • 5. Wang YZ, Carrasquillo JP, McCord E, Vidrine R, Lobo ML, Zamin SA, et al. Reappraisal of lymphatic mapping for midgut neuroendocrine patients undergoing cytoreductive surgery. Surgery. 2014 December 01;156(6):149-3. • 6. Watzka FM, Fottner C, Miederer M, Weber MM, Schad A, Lang H, et al. Surgical Treatment of NEN of Small Bowel: A Retrospective Analysis. World J Surg. 2016 March 01;40(3):749-58. • 7. Wang YZ, Diebold A, Woltering E, King H, Boudreaux JP, Anthony LB, et al. Radioguided exploration facilitates surgical cytoreduction of neuroendocrine tumors. J Gastrointest Surg. 2012 March 01;16(3):635-40.