Borderline Resectable Carcinoma Pancreas

Borderline Resectable Carcinoma PancreasBorderline Resectable Carcinoma Pancreasi.e. T3N0M0 or T3N1M0 (7th AJCC )

Defined as Ca pancreas with involvement of major peripancreatic vessels with possiblity of curative resection

Mortality and complication rates after R0 resection similar to resectable disease (T1/T2 N0 M0)IntroductionAdenocarcinoma of the pancreas is the fourth highest cause of cancer-related death among men and women in the USA and worldwide

8090 % of patients have locally advanced (30-40%) or disseminated disease at presentation

15-20% able to undergo complete surgical resection with negative margins

Median overall survival of patients who undergo complete resection with negative margins ranges between 12 and 26 months

Median overall survival of 5 to 6 months in unresectable diseaseJemal A, Siegel R, Xu J, Ward E (2010) Cancer Statistics 2010. CA Cancer J Clin 60:2273003Approximately one third of patients presenting with locally advanced pancreatic cancer will be marginally or borderline resectable

Free surgical margins are difficult to attain, owing to the close anatomical relationship between the pancreas and the main visceral vessels

Even microscopic, positive surgical margins have a negative impact on survival, and patients in such situations have the same dismal prognosis as patients who do not undergo resection and are treated with chemoradiotherapy only

1. What is the definition of borderline resectable pancreatic cancer?2. Radiological workup with computer tomography (CT) and magnetic resonance imaging (MRI). Is there a place for positron emission tomography (PET)-CT?3. What does endoscopic ultrasonography (EUS) add?4. Is it necessary to obtain a tissue biopsy of the tumor? What is the preferred method?5. Is a staging laparoscopy necessary?6. What are the possible chemotherapy combinations in the neoadjuvant setting?7. What is the place of neoadjuvant chemoradiation?8. What is the place of chemotherapy followed by chemoradiotherapy?9. Surgical therapy controversies:9.1. Is there any advantage in an extended versus standard lymphadenectomy in duodenopancreatectomy for pancreatic head cancer?9.2. What is the place of vascular resection and reconstruction?10. What is the place of chemotherapeutic treatment after resection?Evolving Assessment and Definition ofBorderline Resectable Pancreatic CancerIn the past, the determination of whether a pancreatic cancer was resectable, unresectable, or borderline resectable was made at surgical exploration

The development of modern imaging techniques with improved resolution has allowed for the preoperative staging of patients. Institutions vary in the use of these techniques and the criteria that are used to stratify patients.

There is no definite consensus on which approach is best. The common theme is to use some combination of complementary imaging modalities to define the size, geometry,and extent of vascular involvement of disease.Rational of defining borderline resectable pancreatic ductal adenocarcinoma as a unique entity is based on 4 clinical observationsComplete resection of the primary tumor and regional lymph nodes is mandatory for long-term survival

The incidence of margin-negative resection following surgery de novo decreases with increasing involvement SMV-PV and SMA

Resection of the SMV-PV and hepatic arterybut not the SMAat pancreatectomy is associated with acceptable outcomes

Chemotherapy and chemoradiation may be used to select patients with favorable physiology and tumor biology who may benefit from aggressive operationsWithin this context, borderline resectable tumors are best conceptualizedthose that involve the mesenteric vasculature to a limited extentthose for which resection, while possible, would likely be compromised by positive surgical margins in the absence of preoperative therapy or vascular resection

A uniformly accepted set of criteria that define patients with borderline resectable PDAC does not exist

Definition2 most commonly cited definitions are those proposed byMD Anderson group

Americas Hepatopancreatobiliary Association (AHPBA)/Society for Surgery of the Alimentary Tract (SSAT)/Society of Surgical Oncology (SSO, and modified by the NCCN)Sites of venous invasion that may be potentially resectable

M D Anderson definitionBorderline tumors are defined as those that abut the SMAabut or encase the CHA over a short segmentocclude the SMV-PV confluence, with suitable vein above and below such that venous reconstruction is possibleAmerican Hepato-Pancreato-Biliary Association 2008 Consensus Conference Borderline resectable tumors areInvolvement, abutment, encasement, or thrombosis of the SMV or portal vein over a short distance with reconstructable vessels above and below the area of involvement and no arterial involvement;

GDA involvement up to or around a short segment of the hepatic artery

Abutment of the SMA with less than 180-degree involvement.Comparison of different radiological definitionAHPBA MD Anderson NCCN 2012Intergroup trial 2013SMV-PV Abutment, encasement ,or occlusionOcclusion Abutment with impingement or narrowing Interface between tumor and vessel measuring 180. or greater of the circumference of the vessel wall, and/or reconstructabled occlusion SMA Abutment Abutment Abutment Interface between tumor and vessel measuring less than 180. of the circumference of the vessel wall CHA Abutment or short-segment encasement Abutment or short-segment encasement Abutment or short-segment encasement Reconstructabled, short-segment interface between tumor and vessel of any degree Celiac trunk No abutment or encasement Abutment No abutment or encasement Interface between tumor and vessel measuring less than 180.of the circumference of the vessel wall Modified M D Anderson classificationIn addition to this established anatomic definition of borderline resectable they has included two additional subsets of patients who often escape accurate classification into a specific stage of diseaseType A: Anatomical borderline resectableType B: Patients with indeterminate or questionable metastatic diseaseType C: Patients with a suboptimal performance status or extensive medical comorbidities requiring prolonged evaluation that preclude immediate major abdominal surgery

Inclusion of these latter two groups into the borderline resectable category allows for accurate staging of all patients who present with newly diagnosed pancreatic cancer and specifically, the identification of a subset of patients who are marginally resectable or operable based on anatomic or clinical criteria

Such classification of patients by stage is necessary to allow for stage-specific therapy both on- or off-protocolRadiological workupThere is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer

A clue to determining the resectability of pancreatic cancer in the absence of metastatic disease is the assessment of vascular invasion, which is best displayed by CT

CT is the technique of choice for determining the first intervention, allowing a TNM staging evaluation in a single non-invasive examinationBuchs NC et al (2010) Vascular invasion in pancreatic cancer. Imaging modalities preoperative diagnosis and surgical management. World J GastroenterolPancreas protocol CT should be a dual-phase exam with images obtained during thePancreatic phase:Intermediate between the arterial phase and venous phaseIdeal for both detection and local staging of pancreatic adenocarcinomaHepatic phase:For hypovascular metastasisNoncontrast images For detecting calcifications and confirming that enhancement is present on postcontrast images

Recent studies found that images obtained in the arterial phase are unnecessary, as they are inferior to those obtained in the pancreatic phase or the hepatic phase for detection and staging of pancreatic adenocarcinomaIchikawa T et al. (2006) MDCT of pancreatic adenocarcinoma: optimal imaging phases and multiplanar reformatted imaging. AJR Am J Roentgenol 187:15131520Lus Five grade scaleMost commonly used system for predicting vascular invasion by pancreatic adenocarcinoma

Based on the degree of contact between tumor and a vessel

Tumor contiguity with >50% of the perimeter of a vessel was found to be the optimal threshold for predicting vascular invasion, with a sensitivity of 84% and specificity of 98%

Tear drop SMV is found to be highly specific sign for vascular invasion

Lu DSK et al. (1997) Local staging of pancreatic cancer: criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT. AJR Am J Roentgenol 168:14391443Five grade scaleCategory Description Comment Grade 0 No contiguity of tumor with a vessel Vascular invasion in 0% of cases Grade 1 Tumor contiguous with 75% of the circumference of a vessel or any vessel constriction Vascular invasion in all cases Predicting vascular invasion by tumor using 50% tumor contiguity with vessel as thresholdAuthors Sensitivity (%) Specificity (%) Lu et al8498OMalley et al4699Nakayama et al. veins only 7186Nakayama et al. arteries only 7879Li et al. veins only 49100Li et al. arteries only 9791Overall resectability and need for venous resectionCategory Description Overall Resection RateResection without venous resectionA Fat plane separates the tumor and/or the normal pancreatic parenchyma from adjacent vessels 10095B Normal parenchyma separates the hypodense tumor from adjacent vessels 10095C Hypodense tumor is inseparable from adjacent vessels, and the points of contact form a convexity against the vessels 8955D Hypodense tumor is inseparable from adjacent vessels, and the points of contact form a concavity against the vessels or partially encircle the vessels 4747E Hypodense tumor encircles adjacent vessels, and no fat plane is identified between the tumor and the vessels 00F Tumor occludes the vessels 00Loyer EM et al. (1996) Vascular involvement in pancreatic adenocarcinoma: reassessment by thinsection CT. Abdom Imaging 21:202206Lymph Nodal AssessmentRoche et al compared theassessmentof peripancreatic lymph nodes usingCTwith histopathologicassessmentof inpatientswith pancreaticductaladenocarcinoma

Sensitivity of 14% and a specificity of 85% if a short-axis diameter of 10 mm is used as the sole criterion for tumor involvementUsing a short-axis diameter of 5 mm as threshold increased sensitivity to 71%, but reduced specificity to 64%. Morphologic features (rounded nodes, clustered nodes, nodes with no fatty hilum) were not found to be helpfulThe authors concluded that in a patient with pancreatic adenocarcinoma, the finding of enlarged peripancreatic lymph nodes on CT should not preclude attempted resection

Roche CJ et al. (2003) CT and pathologic assessment of prospective nodal staging in patients with ductal adenocarcinoma of the head of the pancreas. AJR Am J Roentgenol 180:475480Metastasis AssessmentLiver and peritoneal surfaces are common sites for distant metastases

When a lesion is large, the diagnosis of metastatic disease to the liver is usually straightforward.

A commonly encountered problem when staging cancer patients with CT is the presence of small ( .05)T-stagingaccuracy was 67% (eight of 12) withneoadjuvantCTRT and 95% (19 of 20) without it, with a significant difference (P = .0185)They concluded that NeoadjuvantCTRT reduces the accuracy of tumor restaging after treatment ofpancreaticheadcancer, but this effect is not so great as to affect the determination ofresectabilityKim YE et al (2009) Effects of neoadjuvant combined chemotherapy and radiation therapy on the CT evaluation of resectability and staging in patients with pancreatic cancer. Radiology 250(3):758765MRISuperior to CT for the detection of liver metastases

But accuracy of this technique in diagnosing vascular invasion is quite similar to that of CT

Reserve this expensive and time-consuming technique for those patients with iodine allergies, renal insufficiency, pregnancy or inconclusive CT resultsSoriano A et al (2004) Preoperative staging and tumour resectability assessment of pancreatic cancer; prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging and angiography. Am J Gastroenterol 99:492501PETAccurate in diagnosing small tumors (< 2 cm), peritoneal implants and metastases

Not useful for evaluating lymph nodes or vascular invasion.

Differentiate inflammatory pathologies from tumoral pathologies and malignant pathologies from benign pathologies with a sensitivity of 85100 % and a specificity of 6999 %, values that are often higher than the CT values.

Thus, the coupling of PET with CT (PETCT) provides more information than CT alone

Complementary to CTSendler A et al (2000) Preoperative evaluation of pancreatic masses with positron emission tomography using 18F-fluorodeoxyglucose: diagnostic limitations. World J Surg 24:11211129EUSHighest detection rate of tumors < 20 mm in size

More accurate than CT for the detection of venous invasion.

Not a first-line diagnostic technique

However, once a diagnosis is suspected with inconclusive CT findings or no pancreatic head massTo confirm the presence of a tumorAssess vascular invasion by DopplerSpecially accurate in detecting PV and SV infiltrationLess sensitive in detecting SMA and SMV involvementPermit the accurate placement of a needle biopsyVaradarajulu S et al (2005) The role of endoscopic ultrasonography in the evaluation of pancreatico-biliary cancer. Gastrointest Endosc Clin N Am 15(3):497511EUS-FNAC has a PPV in the range of 9297% but a NPV of only 4050%

Considered superior to nonhelical or single-detector CT in detecting small (< 2 cm) primary pancreatic cancers, although this difference is not significant compared with MDCTStessin AM et al (2008) Neoadjuvant radiation is associated with improved survival in patients with resectable pancreatic cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry. IntJ Radiat Oncol Biol Phys 72(4):11281133For detection of peripancreatic lymph node metastasis in pancreatic cancer, endoscopic sonography is superior to CT

Morphologic features such as absence of an echogenic center and a rounded rather than ovoid outline suggest malignant invasion, even in normalsized nodes.

However, due to the limited field of view of endoscopic sonography, CT is better at detecting paraaortic and mesenteric nodesHoffman JP et al(1998) Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol 16(1):317 23Tissue biopsyTissue diagnosis prior to the start of treatment is considered mandatory by most authors and institutions when the patient is considered for neoadjuvant treatment.

The three available techniques for pancreatic cancer tissue biopsyERCPTransabdominal FNAEUS-guided FNA.

EUS-FNA has the highest sensitivity, specificity, diagnostic accuracy and positive and negative predictive values

The possibility of tumor dissemination is lower with EUS-FNA than with percutaneous image-guided FNA

EUS-FNA has a low complication rate (12 %), with complications from this procedure including bleeding, pancreatitis and perforation.Micames C et al (2003) Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA versus percutaneous FNA. Gastrointest Endosc 58:690695STAGING LAPAROSCOPY: ROUTINEOR SELECTIVE?No level 1 data

Despite its apparent benefits, the value of staging laparoscopy is not universally accepted

Opinions range from recommending its routine use for all patients before laparotomy to not performing laparoscopy in any circumstance

A complimentary staging method to overcome this shortfall is necessary, and ideally one that accurately upstages a patients pancreatic cancer with the least physical insult

ProsInadequate sensitivity for occult small-volume metastatic disease even by high quality CT

Accurate laparoscopic examination can be performed efficiently and does not affect subsequent resection

Hospital stays, costs, and overall morbidity are obviously reduced when an unnecessary open laparotomy is avoided for unresectable or occult metastatic disease.29

Protects the quality and comfort for the patients final stage of life

Numerous studies have consistently shown that up to one-third of patients thought to be resectable by state-of the-art imaging will be disqualified for surgery at laparoscopic staging

Some suggest adding laparoscopic ultrasonography to extend the yield, as is possible by identifying and sampling small intrahepatic metastasesConsCritics argue that most studies probably overestimate the value of staging laparoscopy

They maintain that if todays highest-quality imaging is properly used, only a minority of patients will actually benefit

They counter the cost-effectiveness argument by claiming that excess resources are used to achieve the occasional success

Selective ApproachSome evidence has emerged to support a selective approach to staging laparoscopy

The goal has become optimizing yield while preserving the diagnostic value of staging laparoscopy by obeying specific clinical selection criteria

Tumor location is perhaps most important. Distinct subsets of peripancreatic tumors warrant staging laparoscopy such as large (>3 cm) primary tumors, and all lesions in the neck, body, or tail of the pancreas.32

If high-quality imaging is in any way suggestive of occult metastatic disease (equivocal peritoneal/liver metastases, low-volume ascites), staging laparoscopy makes sense.

Even subtle clinical indicators of advanced disease, such as marked weight loss and pain, hypoalbuminemia, and high CA 19-9 levels, may warrant laparoscopy.33White R et al (2008) Current utility of staging laparoscopy for pancreatic and peripancreatic neoplasms. J Am Coll Surg 206:445450Consensus Statement for apparent resectable pancreatic cancer, staging laparoscopy should be used selectively on the basis of clinical predictors that optimize yield i.e.Pancreatic head tumors of >3 cmTumors of the pancreas body and tailEquivocal findings on CT scanHigh CA 19-9 levels (>100 U/mL)Neoadjuvant treatmentAim:Increase resectability ratesEvaluate the patients sensitivity to treatment and increase survival

Optimal neoadjuvant therapeutic strategy in potentially resectable pancreatic cancer - controversial.

Chemotherapy and chemoradiotherapy are the main optionsGillen S (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7(4):e1000267In a recently published meta-analysis111 studies (4,394 patients)56 of which were phase I and II studies of patients with resectable and unresectable/ borderline resectable pancreatic cancer were includedNeoadjuvant chemotherapy (96.4 %)Radiation therapy (93.4 %)

Results33.2 % of the patients initially presenting as unresectable/borderline resectable cases underwent curative surgery after neoadjuvant treatment. The median survival of these patients after resection was 20.5 months, which was similar to that of patients with initially resectable tumors. Despite the heterogeneity of the included studies, these data suggest the importance of re-evaluating all patients with locally advanced/borderline resectable tumors after neoadjuvant therapy for selecting potential candidates for surgery.

Gillen S et al (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7(4):e1000267

Neoadjuvant treatment is particularly important in patients with borderline resectable tumors, which are those that have a greater chance of being completely resected after neoadjuvant treatment

A series published by the M. D. Anderson Cancer Center160 marginally resectable pancreatic cancer patients who were classified as marginally resectable 125 (78 %) received neoadjuvant therapy (chemotherapy, chemoradiation or both) and were reevaluated for surgerySixty-six (41 %) of these patients underwent pancreatectomy following neoadjuvant therapy62 (94 %) exhibiting negative margins at surgeryThe median survival for the 66 patients who underwent surgery after neoadjuvant treatment was 40 months, whereas the median survival for the 94 patients who were to undergo pancreatectomy was 13 months (p = 0.001)

They concluded that this neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.Katz MH et al (2008) Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 206(5):833848Neoadjuvant chemoradiationA recent extensive review of radiochemotherapy in the multimodal treatment of pancreatic cancerOnly phase II studies or a retrospective analysis

Resectability rate10-20% in initially unresectable tumors36-74% in borderline resectability tumors

The local recurrence rates are not always reported, but the available data are consistent with a notably low incidence of this event: 6 -26 % Brunner TB et al (2010) The role of radiotherapy in multimodal treatment of pancreatic carcinoma. Radiat Oncol 5:6476Role of CT followed by CT/RT?Another strategy in the neoadjuvant-based treatment of locally advanced pancreatic cancer is the use of chemotherapy followed by chemoradiotherapyThe purpose of this approach is to select those chemotherapy patients who will benefit from chemoradiotherapy and those who have not experienced disease progression following chemotherapy.The Groupe Cooperateur Multidisciplinaire in Oncologie (GERCOR) published data for a series of 181 patients from phase II and III studies of locally advanced pancreatic cancer who had been treated with gemcitabine-based chemotherapy followed by chemoradiotherapy (55 Gy RT plus 5-FU in continuous infusion)53 patients (29.3 %) developed metastases in the first 3 months of chemotherapy and, therefore, were not eligible for chemoradiotherapyOf the remaining 128 (70.3 %) whose disease had progressed, 72 (56 %) received chemoradiotherapy (group A), and 56 (44 %) continued with chemotherapy (group B)In groups A and B, the median PFS values were 10.8 and 7.4 months, respectively (p = 0.005), and the median OS values were 15 and 11.7 months, respectively (p = 0.0009).Huguet F et al (2007) Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 25(3):326331Another study from the M. D. Anderson Cancer Center323 consecutive patients with locally advanced CA Pancreasereceived treatment with chemoradiotherapy or induction chemotherapy followed by chemoradiotherapy247 patients received chemoradiotherapy as their initial treatment76 patients began with gemcitabine-based chemotherapy for 2.5 months. The patients received a single dose of 30 Gy RT followed by 5-FU concurrent continuous infusion (41 %), gemcitabine (39 %) or capecitabine (20 %)The median OS and PFS were 8.5 and 4.2 months, respectively, in the chemoradiotherapy group, and 11.9 and 6.4 months, respectively, in the chemotherapy followed by chemoradiotherapy group (p\0.001)There were no differences in the patterns of relapse (local and remote) between the two groups.

Krishnan S et al (2007) Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer 110(1):4755The ECOG 1200 phase II trial directly compared chemoradiotherapy with induction chemotherapy followed by chemoradiotherapy and surgery, aiming to assess posterior free margins in patients with borderline resectable pancreatic cancer

The study was closed early because of low recruitment.

Preliminary data was in favor of induction CT followed by CT/RTLandry J et al (2010) Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol 101(7):58759In summary, neoadjuvant CT could increase the chances of resection in some patients, thus prolonging their survival to match that of patients with tumors that are resectable from the beginning

However, the field needs to identify treatment schemes that deliver better results in these patients and complete randomized studies with different drug combinations in addition to comparing neoadjuvant chemotherapy with other preoperative treatment strategies.In summary, the published studies investigating induction CT followed by CT/RT are promising because they suggest that CT may identify those patients who will benefit the most from CT/RT

However, the benefit and safety of this approach should be evaluated in RCT and compared with the other neoadjuvant treatment optionsVascular resection and reconstruction atpancreatico-duodenectomy: technical issuesLeast standarizedLess frequently addressed in the literature

Management of the portal veinDepending on the site of tumor invasion of the SMV-PV, extent of venous resection required

Different technical options for resection and reconstruction are available.

Tangential resection is possible when the lesion is adherent to a small part of the lateral or posterior wall of the PV and SMV. Repair is accomplished with vein patch harvested from the great saphenous vein or elsewhere if the venous lumen is significantly narrowed.

When a segment of the PV has to be sacrificed, primary end-to-end anastomosis should be made with preservation of all venous branches, including the splenic vein, whenever feasible without using an interposition graft.

The resection and reconstruction of PV/SMV should be deferred until the rest of the operative specimen has been completely detached from all the surrounding structures including the SMA, and proximal and distal controls must be secured for the PV, SMV and splenic veinTo avoid the need for venous anastomosis before the removal of the specimenMinimize the time for venous occlusion

Concurrent inflow occlusion of the SMA at the same time as venous clamping is frequently employed to reduce small bowel edema, making subsequent biliary and pancreatic reconstruction less difficult.

Systemic heparinization at the time of venous resection and reconstruction is not a routine practice, but when considered necessary, 2500 - 5000 U could be given at the time of clamping.

Anticoagulation after surgery is adequate with aspirin alone, but the patient should be put on heparin, followed by coumadin, if clot is found on postoperative imaging studiesUnder normal circumstances, a loss of 2 cm or less of the PV/SMV needs no additional maneuver before an end-to-end venous anastomosis could be done without tension

With extensive mobilizations which allow the maximal cephalad displacement of the distal SMV stump, plus the division of the SV to improve the longitudinal mobility of the PV/SMV, vein graft can be successfully spared even for a segmental loss of 7 to 10 cm

On the other hand, some authors advocated the use of an interposition graft to bridge the ends of the PV/SMV instead of a routine sacrifice of the SVManagement of the splenic veinThe SV is divided when tumor invasion at its junction with the PV is evidentextra mobility for a direct end-to-end anastomosis between the PV and SMV is necessary,rarely to provide better exposure for a thorough nodal clearance and soft tissue dissection at the proximal 3 to 4 cm of the SMA.

After division of the SV, a mandatory reconstruction is not a universally accepted practice. Some claimed that most patients would have no problem as the venous flow from the spleen and stomach could return to the systemic vein or the SMV through the short gastric vein and the esophageal vein

In fact, recent studies on the anatomical relationship between the inferior mesenteric vein (IMV), SV and SMV using helical CT venography demonstrated that 48.3% to 68.5% of a normal population have their IMV joined to the SV, thus sparing the IMV/SV confluence when the SV is ligated closely to the PV

On the other hand, a significant proportion of patients have their IMV joining to either the SMV (18.5% to 31%) or the junction between the SMV and SV (7.6% to 13.8%), and would run a potential risk of segmental left-side venous hypertension with resulted splenomegaly, hypertensive gastropathy, esophageal varices and hemorrhage with SV ligation.Although the number of patients studied was small, they concluded that left-side venous hypertension is not an inevitable event after SV ligation without reconstruction.

Many had adopted a selective approach for SV reconstruction. In the absence of an intact natural confluence between the SV and IMV, the two veins are anastomosed together with 8-0 non-absorbable sutures so that the venous drainage of the spleen and gastric remnant is preserved without making the more difficult anastomosis between the shortened SV and PV.

Using surrogate markers including the changes of platelet count and spleen volume before and after surgery, Ferreira et al found that such selective approach is feasible in obviating venous congestion during a short term follow-up

Graf O,. Anatomic variants of mesenteric veins: depiction with helical CT venography. AJR Am J Roentgenol 1997Strasberg SM. Pattern of venous collateral development after splenic vein occlusion in an extended Whipple procedure : comparison with collateral vein pattern in cases of sinistral portal hypertension. J Gastrointest Surg 2011Management of SMV and itsfirst order branchesWhen the main trunk of the SMV and the junction of the ileal and jejunal branches are invaded by the tumor, segmental resection follow by reconstruction is necessary

As the small bowel would have adequate venous return if only one of the two major branches remains intact, the jejunal branch is usually sacrificed as it is usually posteriorly located with a thin wall, and difficult to access for the anastomosis to the SMV trunk.

While the ileal branch is always the preferred choice for reconstruction after segmental excision, additional consideration must also be given to its caliberBased on the experiences gathered at the MD Anderson Cancer Center, an ileal branch of adequate caliber should have a diameter of 1.5 times larger than that of the SMA as seen on CT scan.

Katz MH. Anatomy of the superior mesenteric vein with special reference to the surgical management of first-order branch involvement at pancreaticoduodenectomy. Ann Surg 2008Selection of vein substitutionFollowing segmental resection of the PV/SMV truck, interposition graft with different materials is occasionally required.

In a review, primary anastomosis (88.6%) was used most frequently, followed by autologous vein graft (9.7%) and synthetic vein graft (1.7%)

The use of autologous graft is largely preferred over synthetic graft as the operative field after PD is potentially contaminated, especially if anastomotic leakage does occurWhile the preferred autologous vein varies according to individual centers, the accessibility of the vein graft, ease of procurement and the absence of long-term sequelae after its harvesting are the prime considerations for selection

The use of internal jugular vein, superficial femoral vein and IMV has been reported but gained limited enthusiasm.

At the Mayo Clinic in Rochester, the left renal vein (LRV) is used to re-establish the venous continuity when a primary end-to-end anastomosis fails

Tseng JF et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004Fleming JB. Superficial femoral vein as a conduit for portal vein reconstruction during pancreaticoduodenectomy. Arch Surg 2005.

Reports on the outcome of artificial graft are sparse as most surgeons would use it as the last option. Theoretically, the use of PTFE has the advantage that the external reinforcement ring could help to maintain a better patency when used in the high-flow, low-pressure and high-volume portal system.An anecdotal report made by Stauffer et al showed encouraging results. Postoperatively estimated cumulative graft patency at one month for their 9 patients was 100%, as compared with 86%, and 60% after autologous vein and primary anastomotic repairs, respectivelyRetrospective experiences reported elsewhere suggested differently. In a series of 18 patients with PTFE reconstruction, the actual rate of thrombosis was 33%, as compared to a combined 12% in 13 primary end-to-end and 29 lateral venorrhaphy repairs. There was no statistically significant difference. None of the 4 patients in the same series who had used LRV for reconstruction developed graft thrombosisIn summary, adequate preop assessment of any patient planning for PD must include a CT which had been scrutinized by the surgical team involvedExaminations should focus not only the relationship between the lesions and the neighboring major vessels, but also a thorough elucidation of the vascular anatomy, such as the orifices of the celiac axis and SMA, the presence of replaced right hepatic artery and the relationship between the SMV and its major tributaries. Even if major arterial stenosis is not detected on preoperative CT, a trial clamping of the GDA, and confirmation of a good hepatic arterial flow before committing to proceed with a PD should be taken as a routine.Furthermore, careful palpation along the right distal border of the hepato-duodenal ligament, supplemented by intraoperative Doppler ultrasound, would be advisable to rule out the presence of a replaced or accessary right hepatic artery missed by CT.Is there any advantage in an extended versus standard lymphadenectomyThe idea of resecting extended soft tissue and lymph nodes to decrease local recurrence and increase survival has been supported by some groups.Four prospective randomized trials were conducted to compare standard and extended lymphadenectomy in terms of survival and morbility and mortality benefits. Two multi-institutional studies were performed in Japan and Italy The other two studies were performed in large volume institutions in the USAAll four studies concluded that extended lymphadenectomy was feasible, increased surgical time, carried morbidity and mortality rates similar to those for standard lymphadenectomy and exhibited no benefit for long-term survival.These studies also detected a worsening in the quality of life for the extended lymphadenectomy group primarily because of severe diarrhea that improved with time. The diarrhea was attributed to the circumferential resection of lymphatic and neural tissue around the SMA.

There is no survival benefit from extended lymphadenectomy associated with duodenopancreatectomy for pancreatic carcinoma, and patient quality of life may worsen after this procedure.

OutcomeGivonni et alReview of literature from January 2000 to March 2008final study population was composed of 12 articles

Giovanni Ramacciato et al. Does Portal-Superior Mesenteric Vein Invasion Still Indicate Irresectability for Pancreatic Carcinoma? Ann Surg Oncol (2009) 16:817825. Study PopulationsStudy Year Inclusion period No. patients : Pancreatic CANo. patients : PV/SMVR Shibata et al.4 200119831998 7428Kawada et al.5 200219901997 4328Nakagohri et al.6 200319922001 8133Capussotti et al.7 200319881998 10022Howard et al.8 20033613Poon et al.9 200419982002 5012Zhou et al.10 200519992003 3232Jain et al.11 200519822004 4848Riediger et al.12 200619942004 12540Shimada et al.13 200619962004 14986Al-Haddad et al.14 200719982005 7622Kurosaki et al.15 200819872005 7735Total 891399Intraoperative findingsStudy Type of procedure Operative Blood Length of PV/SMV PV/SMV occlusion time (min) loss (ml) resected (cm) (min) Shibata et al.4 PD 82%, TP 11% DP 7% 4531583Kawada et al.5 PD 71%, PPPD 11%, TP 18% 5513083Nakagohri et al.6 PD 75%, DP 25%a Capussotti et al.7 PD 100% 308b Howard et al.8 PD 46%, PPPD 54% 4081567Poon et al.9 PD 92%, PPPD 8% 660800Zhou et al.10 PD 100% 35314203.92040 Jain et al.11 Total PD 46%, subtotal PD 54% 3907001.55 815 Riediger et al.12 PD 19%, TP 8%, PPPD 74%b 500b Shimada et al.13 PD 56%, TP 6%, PPPD 38% 6671686Al-Haddad et al.14 PD 86%, TP 9%, DP 5% Kurosaki et al.15 PD 100% 51012003b 20.5b Histopathology of resected specimensStudy Venous invasion Resection margins ? Lymphnodal InvolvementPerineural invasionShibata et al.4 7/12 (58.3%) 8 (28.6%) Kawada et al.5 21/28 (75%) 18 (64%) 24 (86%) Nakagohri et al.6 17/33 (51.5%) 8 (24.2%) 32 (97%) 13 (39%) Capussotti et al.7 18/22 (81.8%) 5/6 (83.4%) 15 (68.2%) 17 (77.2%) Howard et al.8 13/13 (100%) 3 (23%) 7 (54%) 8 (62%) Poon et al.9 6/12 (50%) 1 (8.3%) 4 (33.3%) Zhou et al.10 20/32 (62.5%) 5 (15.6%) 25 (78%) Jain et al. 11 0Riediger et al.12 16/29 (55.2%) 13 (32.5%) Shimada et al.13 58/86 (67.4%) 33 (38.4%) 38 (44%) Al-Haddad et al.14 14/19 (73.7%) 13 (59%) Kurosaki et al.15 15/35 (42.9%) 14.30%20 (57.1%) 34 (97.1%) Perioperative results and survivalStudy Hospital Morbidity Mortality Median 1-Year 5-Year stay (days) survival (mo) survival (%) survival (%) Shibata et al.4 9 (32%) 1/28 (4%) 319Kawada et al.5 68.813 (46%) 1/28 (4%) Nakagohri et al.6 2/33 (6.06%) 15589Capussotti et al.7 25.5a 9 (33.3)a 0 (0%) 15a 68.5a 8.4a Howard et al.8 147 (54%) 1/13 (7.7%) 1383Poon et al.9 155 (41.7%) 0/12 (0%) 19.5Zhou et al.10 10 (31.3%) 0/32 (0%) 59Jain et al.11 128 (16.7%) 3/48 (6.25%) 18Riediger et al.12 16a 22 (42%)a 2 (4%)a 2210.9Shimada et al.13 441/86 (1.2%) 1412Al-Haddad et al.14 0/22 (0%) 41.9b Kurosaki et al.15 12 (34%) 1/35 (2.9%) 20Perioperative Results and SurvivalMortality rates ranged from 0 to 7.7%.

Regarding specific mortality rates, in 11 studies no deaths related to the PV/SMV resection and reconstruction were reported, whereas in 1 study (as mentioned above), one patient developed portal and died 2 days after the second operation

The mean hospital stay ranged from 12 to 68.8 days

Complication rates for pancreatectomy with PV/SMV resection ranged from 16.7% to 54%

The most frequent complications were pancreatic fistula, delayed gastric emptying, and intra-abdominal abscess, as in standard pancreatectomies

Eight studies that compared morbidity rates after pancreatectomy with or without PV/SMV resection reported no differences between the two procedures regarding complication rate

In 11 studies, no specific complications for the venous resection and reconstruction were reported, whereas 1 study reported 1postoperative thrombosis of the anastomotic site of the PV that required reoperation and led the patient to death

Median survivals after pancreatectomy combined with PV/SMV resection for pancreatic carcinoma are reported One-year survival ranged from 31% to 83%, and 5-year survival ranged from 9% to 18%ConclusionPancreas protocol CT is investigation of choiceEUS is complementry to CTPreop tissue biopsy is needed when planning for NACT/RTThe optimal strategy for the neoadjuvant treatment of in potentially resectable cases has not been definitively established, although preferred at most centresMeticulous surgical technique for vascular anastomosisEnd to end primary anastomosis is most common reconstruction performedAutologous graft is preffered over synthetic graftPortal vein/superior mesenteric vein resection combined with pancreatectomy is a safe and feasible procedureConclusionIn light of our current knowledge, there is no survival benefit from extended lymphadenectomy associated with duodenopancreatectomy for pancreatic carcinoma, and the quality of life of patients may worsen.

Acceptable morbidity and mortality rates, comparable to those observed for pancreatectomies without venous resections

Furthermore, this procedure has substantially increased the number of patients undergoing curative resection and provides important survival benefits in selected groups of patients

Hence, pancreatectomy combined with venous resection should always be considered in case of suspected tumor infiltration of portal and/or superior mesenteric vein to achieve clear resection margins, in absence of other contraindications for resectionIf a segmental PV or SMV resection of 2 cm or more is required, a primary end-to-end venous anastomosis with preservation of the SV is the primary goal. While autologous vein graft is often elected over synthetic graft, the use of left renal vein or internal jugular vein as the natural venous substitute had gained the most supports

Artificial vascular graft, especially ring-enforced PTFE graft, has received more attention in recent years, their application should remain cautious at present

Thank YouDrawback of these studies:Small numberMethodological problemsNon randomized studiesMany of these studies included heterogeneous patient populations, including both advanced pancreatic cancer and metastatic disease as cases of locally advanced tumors with borderline or marginal resectability.

When the presumed cut ends are judged to be too short for a tension-free venous anastomosis, the first step to overcome the problem is a complete mobilization of the right colon together with its mesocolon, and the root of the mesentery. In addition, the root of the transverse mesocolon is also detached from the anterior surface of the duodenum and pancreas. During PD, the ligament of Trietz, the third and fourth parts of the duodenum, and proximal jejunum should have been mobilized from the posterior abdominal wall.If necessary, the falciform ligament, right coronary ligament and the right triangular ligament could be divided to allow placement of surgical packs to displace the proximal PV stump caudally to further ease the tension at the proposed venous anastomosis during construction.

Both criteria differentiate borderline resectable from unresectable cancers on the basis of radiographic evidence for limited SMA involvement (predicted radiographically by a tumor-SMA interface less than 180) that would allow resection of the tumor without resection of the artery because pancreatectomy with concomitant resection and reconstruction of the SMA has generally been found to be futile2 classifications differ primarily in the extent to which radiographic evidence of tumor involvement of the SMV-PV discriminates borderline resectable primary tumors from resectable ones.

The MD Anderson group, which favors the use of neoadjuvant chemoradiation for both resectable and borderline resectable cancers, considers venous occlusion to represent the cutoff; tumors that radiographically abut (180 interface) the SMV-PV are considered resectable.

In contrast, the AHPBA/SSAT/ SSO considers venous abutment the cutoff; all tumors with any degree of abutment or encasement of the SMV-PV are considered borderline resectable