1、Howard A. Reber, MDProfessor of SurgeryUCLA School of MedicinePancreatic Cancer Surgical Approach in the USA - 2021Agi Hirshberg Center for Pancreatic Diseasesat UCLAPancreatic CancerEpidemiology 2021 - 46,420 new cases in USA2021 - 39,590 deaths4th most common cancer killer2nd most common GI cancer

2、 killer (colon #1)Pancreatic CancerEpidemiology New Cancer Deaths , United States, 2021.Pancreatic CancerEpidemiology Incidence increasing 1% yearlyPancreatic CancerEpidemiology 85% of new cases are advancedLocally advanced: blood vessels (Stage III)Distant spread to liver, lungs (Stage IV)Late Pres

3、entation - Poor SurvivalHowlander et al, SEER Cancer Statistics Review 2021.American Cancer Society, Cancer Facts & Figures 2021.StageIIIIIIIVPercent at diagnosis60%45%30%15%0%Late Presentation - Poor SurvivalHowlander et al, SEER Cancer Statistics Review 2021.American Cancer Society, Cancer Facts &

4、 Figures 2021.24181260Median Survival (mos)StageIIIIIIIV0Even “earlystage diseaseis advancedNo Surgery If.Major blood vessels involved (Stage III)Distant metastases (Stage IV) Some Stage III may be exceptionsPancreatic ResectionDistal Pancreatectomy (no Appleby)Whipple operation (Pancreaticoduodenec

5、tomy)Standard Whipple Standard WhippleRoux-en-Yrarely donePylorus Preserving Whipple Cure rate is same with each. Most resections arePylorus PreservingWhipplesPylorus Preserving WhippleFactors Influencing Survival 182 consecutive patients underwent a Whipple for pancreatic cancer between 1987 and 20

6、05. Patients from 1987-1995 were compared with those from 1996-2005.Study DesignResultsSurvivalBiological factors related to tumorDifferentiationNodal involvementPerineural invasionResection marginsDegree of Tumor DifferentiationActuarial survival estimate for patients with well, moderately, and poo

7、rly differentiated adenocarcinoma of the pancreas (P.001).50%(1987-2005)Lymph NodesNegativePositive28%22%Actuarial survival for node-negative (solid line) and node-positive (dotted line) patients with adenocarcinoma of the pancreas undergoing a pancreaticoduodenectomy (P.001).38%(1987-2005)Perineura

8、l InvasionNegativePositive36%13%Actuarial survival for patients with adenocarcinoma of the pancreas undergoing pancreaticoduodenectomy (P.001).36%(1987-2005)Resection MarginsNegativePositive27%Biologic features of the tumors themselves are the primary determinants of prognosis!27%157 pts(1987-2005)R

9、0R127.4%40.9%76.4%All 182 PtsSurvival for Entire CohortAll 182 Pts(1987-2005)350 ml EBL475 ml EBL35.5%15.8%Blood Loss Influences SurvivalAdjuvant TherapyTreatment given after resection Effort to eradicate any remaining microscopic tumorAll pts in USA receive chemotherapy after resection!Some in USA

10、also get radiation Cancer may involve HA, PV, superior mesentericvein or arteryUNRESECTABLECriteria for ResectionWhy not resect the involved blood vessels?Criteria for ResectionThose with vessel invasion have extensive tumor with microscopic spread that cannot be removed completelyNot seen on preop

11、scans, but experience tells us its thereIf we resect Stage III tumors, the cancer comes back quickly“Downstaging of PaCa Pts given chemotherapy 6-12 mos We try to kill the microscopic tumor first Re-evaluation by CT, CA19-9 Resection then possible in some First reported by our group (1998) Now more

12、widely done in USASo.Effect of Chemotherapy on TumorTumor: 4.4 x 3.8cmPV invasion (+)Tumor: 2.8 x 2.5cm (57% reduction)PV invasion (-)BeforeAfterInitial scan shows SMA involvement6 mos scan looks similarBut patient felt well and CA19-9 fell from 840 to normal.Arch Surg. 2021;146(7):836-843. Donahue

13、TR, Reber HA et alWhen/Whether to Operate?CT ImagingPVSMASVSMVIMVLRVLGASAHAPancreasAdrenalDownstaging of PaCa Survival25+ survivors 5-17 yearsObserved five-year survival rate: 28%13 more close to 5 yrs with no recurrence Possible five year survival rate: 53%Adjuvant TherapyTreatment given after surg

14、ery (Whipple/distal)Effort to eradicate any remaining microscopic tumorStandard approachNeoadjuvant TherapyTreatment given before surgery in pts with resectable disease (Stage I and II)Some in USA recommend this instead of surgery firstAdvantages and disadvantages Theoretical AdvantagesAlmost all pt

15、s have micrometastatic disease at diagnosis 1 cm - 28% have metastases2 cm - 73%3 cm - 94%So almost all pts could benefit. Iacobuzio-Donahue et al 2021 CellTheoretical AdvantagesIf given after surgery, up to 25% may not be treated at all.If given before, more likely to be physically fit and able to

16、tolerate treatment Or treatment may start late if there were complicationsEffect of Adjuvant Treatment Delay on SurvivalIacobuzio-Donahue et al 2021 CellAvoid Treatment Delay After Surgery70%40%Theoretical Advantages of Neoadjuvant TherapyIdentify pts unlikely to benefit from surgery During 2-3 mo t

17、reatment, up to 20% pts show metastases . . or develop poor performance status Is This an Advantage?Is this good or bad? Good. They are spared surgery that would not have helped. orBad. They missed their chance for resection and possible cure.Neoadjuvant Therapy So why has it not become the standard

18、 approach?Several reasons are givenChemotherapy today has little effect in most ptsNeoadjuvant Therapy At most, 1/3 of pts respond to neoadjuvant treatment.So 2/3 would delay resection by 2-3 months, without effective treatment during that time.Disease could progressNeoadjuvant Therapy Although toda

19、y Chemotherapy has little effect in most pts.This could change with more effective neoadjuvant regimens. Or with the ability to selectively choose a regimen specific for the molecular features of each tumorNeoadjuvant RadioTherapy Radiation Therapy (RTx) of unclear value in most ptsRTx definitely decreases local recurrence of cancerBut it does not increase survival in most.Most pts die of distant di