modern surgical considerations for gastric cancer · society for gastric cancer published general...

Original Article

885

From the Department of Surgery University of Nebraska MedicalCenter and Eppley Cancer Center Omaha NebraskaSubmitted April 30 2008 accepted for publication August 6 2008The authors have no financial interest arrangement or affiliationwith the manufacturers of any products discussed in the article ortheir competitorsCorrespondence Aaron R Sasson MD Department of SurgeryUniversity of Nebraska Medical Center 984030 Nebraska MedicalCenter Omaha NE 68198-4030 E-mail asassonunmcedu

Modern Surgical Considerations for GastricCancer

Quan P LyMD and Aaron R Sasson MD Omaha Nebraska

In addition the proportion of proximal gastric can-cers has risen2 Based on data collected by the NationalCancer Database (NCDB) proximal cancer is morelikely to occur in young white men and distal canceris more likely to occur in Asians African Americansand Hispanics The study also indicates that tumor lo-cation may influence treatment Although surgical resection remains the primary treatment modality pa-tients with proximal gastric cancer are more likely toundergo adjuvant therapy particularly preoperativetherapy2 This article focuses on surgical options provides an overview on the diagnostic tests used toassess resectability describes the principles of surgicalresection and presents controversial topics such as la-paroscopic surgery peritoneal lavage and hepatic metas-tasectomy (Table 1)

Determining ResectabilityOnce a patient is diagnosed with gastric adenocarci-noma usually from endoscopic gastric biopsy furtherworkup is needed to assess medical fitness staging andresectability A thorough history and physical exami-nation are cost-effective tools for evaluating comorbidi-ties and performance status Chest radiograph and CT scans of the abdomen and pelvis are gold stan-dards for examining possible metastases or regional lymphadenopathy

Two recent studies reported that the accuracy of en-doscopic ultrasound (EUS) ranges from 57 to 83 forstaging depth of tumor invasion34 and 50 to 78 fornodal involvement35 Therefore EUS with or withoutfine needle aspiration can significantly influence treat-ment selection particularly if neoadjuvant therapy is con-sidered6 However EUS is not indicated in patients withmetastatic disease and its use should be limited to poten-tially resectable cancers

Key WordsGastric cancer surgery laparoscopy

AbstractSurgical resection remains the mainstay of treatment for localizedgastric adenocarcinoma The type and extent of resection dependson tumor location Although the incidence of gastric cancer hasbeen declining a shift has occurred to more tumors involving theproximal compared with the distal stomach Appropriate treat-ment depends on a thorough staging process to exclude the pres-ence of distant metastatic disease Current staging modalitiesinclude high-quality CT scan endoscopic ultrasound PET and laparoscopy The value of peritoneal lavage to detect occult peritoneal disease is under investigation The principles of surgi-cal resection have always included negative resection margins and adequate lymph node examination Controversial topics requir-ing further study include laparoscopic resections and hepatic metastasectomy This review highlights the salient points of cur-rent surgical management of gastric adenocarcinoma (JNCCN20086885ndash894)

BackgroundAlthough gastric cancer has been decreasing globallyover the past decades it remains the fourth most commoncancer type worldwide In the United States it is one ofthe least common cancer types accounting for fewer than2 of all cancers1 In 2008 an estimated 21500 new casesof gastric cancer will be diagnosed and approximately10880 deaths will occur1

copy Journal of the National Comprehensive Cancer Network Volume 6 Number 9 October 2008

JN069_Jrnl_60905LySassonqxd 10908 713 PM Page 885

886 Original Article

Ly and Sasson

Metabolic imaging with PET using 18F-fluo-rodeoxyglucose is used in various malignancies butits role in gastric cancer still must be determinedAlthough PET is 94 sensitive in detecting gastriccancer7 it was found to be less accurate than spiral CT in staging locoregional involvement but betterat diagnosing distant metastases8ndash10 However PETscan detected 5 of 40 (15) positive nodes missed by CT

In a small series of patients (N = 68) PET scanadded diagnostic value in 15 upstaging 6 anddownstaging 97 A meta-analysis comparing PETultrasound CT and MRI determined that PET scan was the most sensitive imaging modality for

detecting hepatic metastases11 PET may also be useful in determining therapeutic response tochemotherapy Ott et al12 found that tumors that responded metabolically on PET correlatedhighly with histopathologic response and betterpatient survival Therefore PET scan should beused in selected cases such as locally advancedtumors in which the metastatic potential is highor in cases for which neoadjuvant treatment is be-ing considered

Patients are deemed resectable if they are med-ically fit have limited involvement of contiguousstructures and have no evidence of distant metas-tases With locally advanced tumors the tail of the


Table 1 Salient PointsTopics Highlights

Diagnostic studies bull History and physical examinationbull Endoscopy and biopsybull CT scan of the abdomenbull Endoscopic ultrasound for potentially resectable diseasebull PET scan helpful in advanced disease with high risk for metastasis and for patients

being evaluated for chemotherapeutic responsebull Diagnosticstaging laparoscopy for patients undergoing neoadjuvant therapy

Surgical resection bull Main principle of surgical oncology is microscopically negative marginsbull Adequate nodal samplings

Lymphadenectomy bull Japanese institutions are performing a D2 for early gastric cancer and a D34 (para-aortic lymph node dissection) for advanced but resectable disease90

bull Western societies (Dutch trial32) found a D1+ is adequate D2 or above has higher morbidity but no significant benefit

bull NCCN guidelines91 recommended at least 15 nodes be examined

J-pouch reconstruction bull Decrease intestinal transit timebull Better quality of life assessments in postoperative months 30-60 with no significance

lt 30 months or gt 60 months

Laparoscopic surgery bull Less invasivebull Risks for port site recurrence and vascular injurybull Feasible for early gastric cancers

Peritoneal lavage bull Additional prognostic informationbull Low yieldbull Further clinical studies needed

Recurrent disease bull Improved survival if an R0 was achievedpalliative gastrectomy bull Patient is medically fit

bull Usual indication obstruction or excessive bleeding

Hepatic metastasectomy bull Improved survival if an R0 was achieved and for patients with metachronous diseasebull Limited hepatic involvement adequate functional residual liver volume

and no extrahepatic disease

Adjuvant therapy bull MacDonald trial87 (SWOG-9008 INT-0116 RTOG-9018 NCCTG-90-41-51 ECOG-6290 CALGB 9195) showed survival benefit with adjuvant chemoradiation

bull Cunningham et al89 (MAGIC trial) showed survival benefit with perioperative chemotherapy

bull Multidisciplinary management is recommended


Original Article 887

Modern Surgical Considerations for Gastric Cancer

pancreas hilum of the spleen head of the pancreasand lateral segment of the liver may be involvedthrough direct extension but these patients are stilldeemed resectable However postoperative morbidityincreases as more organs are resected to achieve neg-ative surgical margins

Some experts have found staging laparoscopy foradvanced gastric cancer to have significant impact ondecision-making especially in patients for whomaggressive surgical treatments are planned1314 Blackshawet al15 reported unexpected metastases found duringstaging laparoscopy in 21 of 258 patients (8) withpotentially resectable gastric adenocarcinoma whereasSarela et al16 reported a much higher rate of occultmetastases found on laparoscopy 85 of 718 (258)patients with gastric cancer who were previous deemedstage M0 based on CT scan

Gastric ResectionThe type and extent of surgical resection depends ontumor location For a tumor involving the antrum orprepyloric area a distal or subtotal gastrectomy is per-formed with approximately 4- to 5-cm grossly negativemargins and reconstructed with a gastrojejunostomyA prospective randomized trial comparing subtotalwith total gastrectomy for tumors in the distal half ofthe stomach found similar oncologic outcomes17 The5-year survival for the subtotal group was 65 com-pared with 63 for the total group Given the tech-nical challenges of total gastrectomy highersplenectomy rate18 and decreased quality of life19 asubtotal gastrectomy is acceptable for distal cancers ifadequate negative margins are obtained

For tumors involving the proximal stomachsignificant controversy exists regarding the optimalsurgical treatment For tumors involving the cardiawithout gastroesophageal junction involvement eithera proximal or total gastrectomy is an option In a non-randomized study comparing them Harrison et al20

report equivalent mortality and survival Despite theequivalent oncologic outcome multiple studies haveshown a significantly higher rate of anastomotic stric-tures and reflux esophagitis with proximal gastrec-tomy21ndash23 Because of the reflux that develops afterproximal gastrectomy the authors prefer to perform atotal gastrectomy for tumors in this location

Proximal gastric cancers with involvement or nearinvolvement of the gastroesophageal junction can be

treated with either gastrectomy or esophagogastrec-tomy (Ivor-Lewis or transhiatal) In a retrospectivereview comparing options Ito et al24 reported no dif-ference in mortality rate but a higher morbidity ratewith esophageal resection However gastrectomy wasassociated with microscopically positive margins in38 of the patients as opposed to 7 for esophagogas-trectomy24 Clearly no single surgery type is best fortumors in this area resection type should be based onability to achieve negative margins with acceptablemorbidity

Although no randomized prospective trials haveassessed optimal surgical margins Bozzetti et al25

noted that surgical resections of 6 cm or greater prox-imally and 3 to 59 cm distally are associated with100 negative margins A few recent studies haveshown worse survivals for patients with positive mar-gins and negative nodes2627 For patients with posi-tive nodes especially those with 5 or more marginpositivity confers no significant survival difference28

Today most surgeons routinely request intraopera-tive frozen section examination of the margins be-fore reconstruction Regardless of type of resectionand length of margins the main principles of surgeryare microscopically negative margins (R0 resection) andclearance of regional lymph nodes in patients with nodistant metastases

LymphadenectomyAlthough uniform consensus is that nodal sampling isnecessary dichotomy exists between Eastern andWestern practices In 1981 the Japanese ResearchSociety for Gastric Cancer published general rulesfor studying gastric cancer and its pathology throughdefining lymph node stations29 Since then numerousstudies have examined the clinical relevance of theextent of nodal dissection in gastric cancer resec-tion Despite the difference in practice the authorshave accepted the following definitions D0 dissec-tion means gastrectomy with any lymph node re-moval that is less than a D1 D1 dissection entailsgastrectomy and resection of the greater and lesseromenta (which would include the lymph node ofstation 1ndash6 right and left cardiac along lesser andgreater curvature suprapyloric along the right gas-tric artery and infrapyloric respectively) D2 dis-section is a D1 plus the anterior leaf of the transversemesocolon and all the nodes along the left gastric




Ly and Sasson

artery common hepatic artery celiac artery splenichilum and splenic artery (station 7ndash11 respectively)30

and D3 dissection is more extensive than D2 because it includes the para-aortic lymph nodes(station 16 Figure 1)31

The extent of lymphadenectomy has beenamong the most controversial issues in gastric can-cer surgery Multiple retrospective reports have foundan improved survival in patients undergoing D1 lym-phadenectomy compared those undergoing D2 andconsequently several prospective randomized trialshave been performed The largest of these was con-ducted by the Dutch Gastric Cancer Group32 After11 years of follow-up the authors reported a 30survival rate for D1 resections which was similar to35 for D2 (P = 53) Any potential survival ben-efit of D2 was offset by an increase in perioperativemortality 10 versus 4 (P = 004) When hospi-tal deaths were excluded survival rates improved to32 for D1 and 39 for D2 (P = 10) with a statis-tically significant decrease in relapse risk favoringD2 In addition to D2 age older than 70 yearssplenectomy and pancreatectomy were factors asso-ciated with increased morbidity and mortality The authors concluded that extended lymph node

dissection could be beneficial if perioperative mor-bidity and mortality could be reduced Similar find-ings were reported from a prospective randomizedtrial conducted by the British Medical ResearchCouncil33

Splenectomy and distal pancreatectomy were partof the Japanese D2 dissection to better evaluate lymphnode stations 10 and 11 However the Dutch trialfound that splenectomy is associated with greater post-operative morbidity32 Similarly multiple studies fromaround the world showed that curative gastrectomywith concurrent splenectomy or pancreaticosplenec-tomy provided no statistically significant survival ben-efit for patients with gastric cancer and that it isassociated with increased pancreatic and infectiouscomplications34ndash41 Splenectomy or pancreaticosplenec-tomy is only beneficial when there is direct extensionof the tumor or very bulky lymph node disease is pres-ent at the splenic hilum41 A recent nonrandomizedphase II trial of pancreas preserving D2 resections re-ported a mortality rate of 31 and a 5-year survivalof 5542

In the United States greater emphasis has beenplaced on number of nodes removed and examinedthan on location In a retrospective review of more


Figure 1A and B Lymph node stations according to the Japanese Research Society for Gastric Cancer2932

Key 1 right cardiac 2 left cardiac 3 lesser curvature 4 greater curvature (4S superior greater curvature 4D distal greater curvature) 5 suprapyloric 6 infrapyloric 7 left gastric artery 8 common hepatic artery 9 celiac axis nodes 10 splenic hilum 11 splenic artery 12 portal hepatis 13 posteriorpancreatic head 14 root of the mesentery 15 transverse mesocolon and 16 para-aortic




than 1000 patients Karpeh et al43 noted that numberof nodes involved has greater prognostic significancethan location Furthermore significance was greatestwhen at least 15 lymph nodes were examined thus thecurrent American Joint Committee on Cancer(AJCC) staging for gastric cancer recommends exam-ining at least 15 nodes for accurate staging44 Althoughthis recommendation is not driven by prospective ran-domized trials (level 1 data) it is supported by largeretrospective studies45ndash47

More recently the ratio of positive nodes tonodes examined was found to have greater prognos-tic significance than absolute number of positivelymph nodes4849 The AJCC stratifies positive lymphnodes as N1 (1ndash6) N2 (7ndash15) or N3 (gt 15)However lymph node ratio identifies subsets of pa-tients with different survival rates within groups49

Lymph node ratio may have a different prognosticvalue because it accounts for patients with fewerlymph nodes and the absolute number of nodal positivity

ReconstructionAlthough most surgeons agree on extent of surgical re-sections for a specific gastric cancer many options areavailable for restoring intestinal continuity Some stud-ies report that a J-pouch reconstruction is more phys-iologic and allows for slower food transition time andthus less dumping and better nutrient absorption50

McAleese et al51 found that patients with J-pouch re-construction had less postprandial pain better nutri-tion and fewer dietary restrictions than those whounderwent standard esophagojejunostomy reconstruc-tion Recently a prospective randomized study comparing esophagojejunostomy with pouch recon-struction after total gastrectomy reported improvedlong-term quality of life in patients who had pouch re-construction but only after 30 months and it lastedfor approximately 2 years52 At 78 months postgastrec-tomy the authors saw no significant difference in anyquality of life assessments between the groups In ad-dition although the authors noted this improvementin assessments they did not find any difference inpostoperative weight number of meals per day orquantity of food consumed Despite other small stud-ies reporting similar benefits of pouch reconstruc-tion53ndash55 no consensus exists as to the optimal methodof reconstruction

Laparoscopic SurgeryIn the past 2 decades laparoscopic surgery has gainedpopularity because it offers less pain shorter hospitalstay and quicker recovery Laparoscopic-assistedBillroth I gastrectomy was introduced 1994 by Kitanoet al56 and surgeons from Japan57 Korea13 and Italy58

have reported outcomes after laparoscopic gastrec-tomy Although they have shown that laparoscopy-assisted distal subtotal and total gastrectomies withlymph node dissection are feasible with acceptable mor-bidities and mortalities most of these patients hadearly gastric cancers In a multicenter study on thelong-term oncologic outcome of laparoscopic gastrec-tomy for early cancers in Japan Kitano et al59 foundthat 5-year disease-free survival was 99 for stage Iand 86 for stage II disease59 The most serious com-plication for this procedure is vascular injury duringlymph node dissection especially when the surgeonis inexperienced60 Although Kitano et al59 did notfind any in their study published case reports describeport site recurrence after laparoscopic gastrectomyespecially in advanced disease61 Despite numerousstudies showing the safety and feasibility of la-paroscopy no randomized prospective trial has shownthe long-term outcome for this procedure thereforeits role for potentially curatable patients still must bedetermined

Peritoneal LavageDespite adequate surgical treatment a common siteof recurrence is peritoneal carcinomatosis62 In 1978Nakajima et al63 found that peritoneal cytology wasa good prognostic indicator of peritoneal recurrenceHowever in a study of advanced gastric cancer with-out metastatic disease Abe et al64 found no corre-lation between peritoneal recurrence and positiveperitoneal cytology The development of peritonealdisease occurred in 22 of patients with negative cy-tology and in 18 with positive The incidence ofpositive peritoneal cytology absent visible peritonealdisease is low (6ndash15)6566 Several studies havereported decreased survival in patients with posi-tive peritoneal cytology6768 These studies report acorrelation between serosal involvement and lymphnode positivity with positive peritoneal lavage

Despite the prognostic significance of positiveperitoneal cytology a recent report from M DAnderson suggests that resection after neoadjuvant




Ly and Sasson

therapy may improve survival in some patients66

Unfortunately the data on peritoneal cytology arefrom retrospective studies performed at single institu-tions which often include patients with macroscopi-cally positive disease

To increase the sensitivity of peritoneal lavagegreat interest has been shown in evaluating the fluidwith biologic markers Asao et al69 showed that car-cinoembryonic antigen (CEA) levels in peritonealwashings negatively correlated with survival and thestudy in 155 gastric cancer patients by Nishiyama et al70 supported the finding that elevated CEA levelin peritoneal washings predicts a shorter interval toperitoneal recurrence

Real-time reverse transcriptasendashpolymerase chainreaction (RT-PCR) was developed to analyze peri-toneal lavages Although CEA enzyme-linked im-munosorbent assay can detect 100 ngg of protein RT-PCR could reliably detect mRNA copiesof CEA in the presence of as little as 100 cells71

The technique is sound but the detection system is stillnot perfect because a molecule specific to all cancercells has not yet been identified CEA is a good testits disadvantages are that not all gastric cancer cellsexpress CEA and some circulating peripheral bloodleukocytes of healthy people express low levels71

Katsuragi et al72 proposed to measure the mRNAlevels of CEA and cytokeratin-20 (CK20) a proteinspecific for cells of gastrointestinal origin SeparatelyCEA and CK20 RT-PCR have a sensitivity of 65and 51 and a specificity of 82 and 81 respec-tively Used together the sensitivity of either genepositivity increased to 81 but specificity decreasedto 8072 Routine peritoneal lavage has not beenuniformly adopted as a staging modality in gastriccancer the authors believe additional clinical studiesare required for widespread acceptance

Recurrent DiseaseRecurrence after curative resection is common espe-cially in advanced cases Surgical intervention in recurrence is usually for palliative reasons and is infre-quently curative in patients with limited disease Themost common palliative surgical interventions are forpatients with intestinal obstruction or excessive bleed-ing In a retrospective review Song et al62 examinedthe role of surgery in the treatment of recurrent gastric cancer and found that only approximately 25

of patients evaluated underwent complete resection ofthe recurrent disease These patients had gastric rem-nant recurrence or hepatic or ovarian metastasesCompared with patients who underwent explorationwith palliative or no other intervention those who un-derwent complete resection had a much better meansurvival duration of 52 versus 13 (palliative) and 87months (laparotomy alone)62

Palliative GastrectomyPatients with stage IV gastric cancer are typically nottreated with surgical therapy but offered systemic treat-ment Management of symptoms caused by primarytumor growth can be managed with various modali-ties including radiation therapy endoscopic inter-ventions or even surgical procedures (eg bypass)The role of gastrectomy in these patients tends to belimited because higher morbidity and mortality are as-sociated with incurable malignancy Several smallstudies have suggested gastrectomy has a survival ben-efit in patients with metastatic gastric cancer73ndash77 Thebenefit is typically reserved for young patients (lt 70years) with limited metastatic tumor burden goodperformance status and resectable tumors Because ofthe apparent selection bias inherent in these studiesit is difficult to draw any meaningful conclusionsHowever with appropriate patient selection and multi-disciplinary discussion a minority of patients withmetastatic disease may benefit from gastrectomy Amulticenter prospective randomized trial comparinggastrectomy with chemotherapy and chemotherapyalone in patients with stage IV cancer is being con-ducted in Japan and Korea78

Hepatic MetastasectomyAs a result of improvements in liver surgery hepaticmetastasectomy has been performed for gastric cancerHowever determining its benefits is difficult becausesolitary liver metastases are rare Linhares et al79 re-viewed his institutionrsquos record and found that isolatedliver metastases occurred in fewer than 05 of casesover 5 years Even in the East the rate of isolated livermetastases from gastric cancer is only 05380

Although rare long-term survivors have beenreported Koga et al81 reported a median survival of 34 months in a series of 42 patients with hepaticmetastases with 8 patients surviving more than 5





years Okano et al82 suggested that synchronous ormetachronous liver lesions without peritoneal or otherdistant metastases should be evaluated Patients withmetachronous liver resection have lower in-hospitalmortality and better 5-year survival than those withsynchronous metastasectomy83 Ambiru et al84 recom-mended attempting complete resection of hepaticmetastases only when residual liver function is ade-quate Similar to the colorectal experience hepaticmetastasectomy for solitary lesions has better outcomethan for multiple nodules but multiple nodules within1 lobe should still be considered83 A negative surgi-cal margin of at least 1 cm is preferable8284 Hepaticmetastasectomy for gastric adenocarcinoma is contro-versial and still requires further investigation

Adjuvant TreatmentDespite potentially curative resection most patientswith gastric adenocarcinoma will experience relapseand die of the disease Past trials using adjuvant ther-apy failed to show a survival advantage compared withsurgery alone Furthermore 2 meta-analyses showedsmall (if any) benefit Therefore surgery alone remainedstandard treatment8586 In 2001 Macdonald et al87

reported the outcome of a Southwest OncologyGroupIntergroup 0116 study that randomized patientswith completely resected (R0) stage IB to IV M0 gas-tric cancer to chemotherapy (5-fluorouracil) followedby concurrent chemoradiation or observation Mediansurvival for patients undergoing chemoradiation was35 months compared with 26 in the surgery-only group(P = 006) Similarly 3-year survival favored the treat-ment arm (50 vs 41 P lt 001)87

After their success with preoperative chemother-apy for esophageal cancer the Medical ResearchCouncil conducted a randomized trial of periopera-tive chemotherapy with observation88 Patients with potentially resectable stage II to IV M0 gastricesophagogastric and lower third esophageal adeno-carcinoma were eligible89 Treatment consisted of 3 cycles of epirubicin cisplatin and fluorouracil pre-operatively and postoperatively Use of perioperativechemotherapy improved 5-year survival from 23(surgery-only) to 36 (treatment arm P = 009)89

These studies represent pivotal changes in the treat-ment of gastric cancer and emphasize the importanceof multidisciplinary management Both postoperativechemotherapy with concomitant chemoradiotherapy

and perioperative chemotherapy improved survivalin patients with resectable gastric cancer they repre-sent 2 acceptable treatment options

ConclusionsAlthough this article did not discuss other modalitiesof therapy for gastric cancer in detail it recommendsthat patients be managed by a multidisciplinary teamSurgical resection remains an integral part of treat-ment however several recent studies have shown thevalue of adjuvant and neoadjuvant treatment Ongoingareas of investigation include improved staging(peritoneal cytology and PET scans) and resectiontechniques (laparoscopy and endoscopic mucosal re-section) and expanded limits of potentially curativeresection (hepatic metastectomy)

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2 Wilkinson NW Howe J Gay G et al Differences in the pattern ofpresentation and treatment of proximal and distal gastric cancerresults of the 2001 gastric patient care evaluation Ann Surg Oncol2008151644ndash1650

3 Bentrem D Gerdes H Tang L et al Clinical correlation of endoscopicultrasonography with pathologic stage and outcome in patientsundergoing curative resection for gastric cancer Ann Surg Oncol2007141853ndash1859

4 Malheiros CA Ardengh JC Santo GC et al Endoscopic ultrasoundin the preoperative staging of gastric cancer correlation with the sur-gical andor pathological findings Arq Gastroenterol 20084522ndash27[in Portuguese]

5 Ganpathi IS So JB Ho KY Endoscopic ultrasonography for gastriccancer does it influence treatment Surg Endosc 200620559ndash562

6 Jones DB Role of endoscopic ultrasound in staging upper gastroin-testinal cancers ANZ J Surg 200777166ndash172

7 Chen J Cheong JH Yun MJ et al Improvement in preoperative stag-ing of gastric adenocarcinoma with positron emission tomographyCancer 20051032383ndash2390

8 Lerut T Flamen P Ectors N et al Histopathologic validation oflymph node staging with FDG-PET scan in cancer of the esophagusand gastroesophageal junction a prospective study based on primarysurgery with extensive lymphadenectomy Ann Surg 2000232743ndash752

9 Yun M Lim JS Noh SH et al Lymph node staging of gastric can-cer using (18)F-FDG PET a comparison study with CT J Nucl Med2005461582ndash1588

10 Lim JS Kim MJ Yun MJ et al Comparison of CT and 18F-FDG petfor detecting peritoneal metastasis on the preoperative evaluationfor gastric carcinoma Korean J Radiol 20067249ndash256

11 Kinkel K Lu Y Both M et al Detection of hepatic metastases fromcancers of the gastrointestinal tract by using noninvasive imagingmethods (US CT MR imaging PET) a meta-analysis Radiology2002224748ndash756




Ly and Sasson

12 Ott K Herrmann K Lordick F et al Early metabolic response eval-uation by fluorine-18 fluorodeoxyglucose positron emission tomog-raphy allows in vivo testing of chemosensitivity in gastric cancerlong-term results of a prospective study Clin Cancer Res 2008142012ndash2018

13 Song KY Kim SN Park CH Tailored-approach of laparoscopicwedge resection for treatment of submucosal tumor near the esoph-agogastric junction Surg Endosc 2007212272ndash2276

14 Nakagawa S Nashimoto A Yabusaki H Role of staging laparoscopywith peritoneal lavage cytology in the treatment of locally advancedgastric cancer Gastric Cancer 20071029ndash34

15 Blackshaw GR Barry JD Edwards P et al Laparoscopy significantlyimproves the perceived preoperative stage of gastric cancer GastricCancer 20036225ndash229

16 Sarela AI Miner TJ Karpeh MS et al Clinical outcomes with laparoscopic stage M1 unresected gastric adenocarcinoma AnnSurg 2006243189ndash195

17 Bozzetti F Marubini E Bonfanti G et al Subtotal versus total gas-trectomy for gastric cancer five-year survival rates in a multicenterrandomized Italian trial Italian Gastrointestinal Tumor Study GroupAnn Surg 1999230170ndash178

18 Gouzi JL Huguier M Fagniez PL et al Total versus subtotal gastrec-tomy for adenocarcinoma of the gastric antrum A French prospec-tive controlled study Ann Surg 1989209162ndash166

19 Davies J Johnston D Sue-Ling H et al Total or subtotal gastrec-tomy for gastric carcinoma A study of quality of life World J Surg1998221048ndash1055

20 Harrison LE Karpeh MS Brennan MF Total gastrectomy is not nec-essary for proximal gastric cancer Surgery 1998123127ndash130

21 Kim JH Park SS Kim J et al Surgical outcomes for gastric cancerin the upper third of the stomach World J Surg 2006301870ndash1876discussion 1877ndash1878

22 Katsoulis IE Robotis I Kouraklis G Yannopoulos P Duodenogastricreflux after esophagectomy and gastric pull-up the effect of the routeof reconstruction World J Surg 200529174ndash181

23 Hsu CP Chen CY Hsieh YH et al Esophageal reflux after total orproximal gastrectomy in patients with adenocarcinoma of the gas-tric cardia Am J Gastroenterol 1997921347ndash1350

24 Ito H Clancy TE Osteen RT et al Adenocarcinoma of the gastriccardia what is the optimal surgical approach J Am Coll Surg2004199880ndash886

25 Bozzetti F Bonfanti G Bufalino R et al Adequacy of margins of resection in gastrectomy for cancer Ann Surg 1982196685ndash690

26 Cascinu S Giordani P Catalano V et al Resection-line involvementin gastric cancer patients undergoing curative resections implicationsfor clinical management Jpn J Clin Oncol 199929291ndash293

27 Cho BC Jeung HC Choi HJ et al Prognostic impact of resectionmargin involvement after extended (D2D3) gastrectomy for ad-vanced gastric cancer a 15-year experience at a single institute J SurgOncol 200795461ndash468

28 Kim SH Karpeh MS Klimstra DS et al Effect of microscopic re-section line disease on gastric cancer survival J Gastrointest Surg1999324ndash33

29 Kajitani T The general rules for the gastric cancer study in surgeryand pathology Part I Clinical classification Jpn J Surg 198111127ndash139

30 DrsquoUgo D Pacelli F Persiani R et al Impact of the latest TNM clas-sification for gastric cancer retrospective analysis on 94 D2 gastrec-tomies World J Surg 200226672ndash677

31 Marrelli D Pedrazzani C Neri A et al Complications after extended(D2) and superextended (D3) lymphadenectomy for gastric canceranalysis of potential risk factors Ann Surg Oncol 20071425ndash33

32 Hartgrink HH van de Velde CJ Putter H et al Extended lymph nodedissection for gastric cancer who may benefit Final results of therandomized dutch gastric cancer group trial J Clin Oncol 2004222069ndash2077

33 Cuschieri A Weeden S Fielding J et al Patient survival after D1and D2 resections for gastric cancer long-term results of the MRCrandomized surgical trial Surgical Co-operative Group Br J Cancer1999791522ndash1530

34 Hartgrink HH van de Velde CJ Status of extended lymph node dis-section locoregional control is the only way to survive gastric can-cer J Surg Oncol 200590153ndash165

35 Fatouros M Roukos DH Lorenz M et al Impact of spleen preser-vation in patients with gastric cancer Anticancer Res 2005253023ndash3030

36 Biffi R Chiappa A Luca F et al Extended lymph node dissectionwithout routine spleno-pancreatectomy for treatment of gastric can-cer low morbidity and mortality rates in a single center series of 250patients J Surg Oncol 200693394ndash400

37 Gil-Rendo A Hernandez-Lizoain JL Martinez-Regueira F et al Riskfactors related to operative morbidity in patients undergoing gas-trectomy for gastric cancer Clin Transl Oncol 20068354ndash361

38 Kulig J Popiela T Kolodziejczyk P et al Standard D2 versus ex-tended D2 (D2+) lymphadenectomy for gastric cancer an interimsafety analysis of a multicenter randomized clinical trial Am J Surg200719310ndash15

39 Yu W Choi GS Chung HY Randomized clinical trial of splenec-tomy versus splenic preservation in patients with proximal gastric can-cer Br J Surg 200693559ndash563

40 Zhang CH Zhan WH He YL et al Spleen preservation in radicalsurgery for gastric cardia cancer Ann Surg Oncol 2007141312ndash1319

41 Kunisaki C Makino H Suwa H et al Impact of splenectomy in pa-tients with gastric adenocarcinoma of the cardia J Gastrointest Surg2007111039ndash1044

42 Degiuli M Sasako M Ponti A Calvo F Survival results of a multi-centre phase II study to evaluate D2 gastrectomy for gastric cancerBr J Cancer 2004901727ndash1732

43 Karpeh MS Leon L Klimstra D Brennan MF Lymph node stagingin gastric cancer is location more important than number An analy-sis of 1038 patients Ann Surg 2000232362ndash371

44 Greene FL Page DL Fleming ID et al eds AJCC Cancer StagingManual 6th ed New York Springer 2002421

45 Lee HK Yang HK Kim WH et al Influence of the number of lymphnodes examined on staging of gastric cancer Br J Surg 2001881408ndash1412

46 Bouvier AM Haas O Piard F et al How many nodes must be ex-amined to accurately stage gastric carcinomas Results from a pop-ulation based study Cancer 2002942862ndash2866

47 Smith DD Schwarz RR Schwarz RE Impact of total lymph nodecount on staging and survival after gastrectomy for gastric cancerdata from a large US-population database J Clin Oncol 2005237114ndash7124

48 Saito H Fukumoto Y Osaki T et al Prognostic significance of theratio between metastatic and dissected lymph nodes (n ratio) in pa-tients with advanced gastric cancer J Surg Oncol 200897132ndash135

49 Marchet A Mocellin S Ambrosi A et al The ratio between metasta-tic and examined lymph nodes (N ratio) is an independent prognos-tic factor in gastric cancer regardless of the type of lymphadenectomy





results from an Italian multicentric study in 1853 patients Ann Surg2007245543ndash552

50 Iivonen MK Mattila JJ Nordback IH Matikainen MJ Long-termfollow-up of patients with jejunal pouch reconstruction after totalgastrectomy A randomized prospective study Scand J Gastroenterol200035679ndash685

51 McAleese P Calvert H Ferguson WR Laird J Evaluation of ldquogas-tricrdquo emptying time in the J pouch compared with a standardesophagojejunal anastomosis World J Surg 199317595ndash599 discus-sion 599ndash600

52 Fein M Fuchs KH Thalheimer A et al Long-term benefits of roux-en-Ypouch reconstruction after total gastrectomy a randomized trialAnn Surg 2008247759ndash765

53 Kono K Iizuka H Sekikawa T et al Improved quality of life withjejunal pouch reconstruction after total gastrectomy Am J Surg2003185150ndash154

54 Iivonen MK Koskinen MO Ikonen TJ Matikainen MJ Emptyingof the jejunal pouch and Roux-en-Y limb after total gastrectomymdasha randomised prospective study Eur J Surg 1999165742ndash747

55 Nakane Y Okumura S Akehira K et al Jejunal pouch reconstruc-tion after total gastrectomy for cancer A randomized controlledtrial Ann Surg 199522227ndash35

56 Kitano S Iso Y Moriyama M Sugimachi K Laparoscopy-assisted billroth I gastrectomy Surg Laparosc Endosc 19944146ndash148

57 Fujiwara M Kodera Y Misawa K et al Longterm outcomes of early-stage gastric carcinoma patients treated with laparoscopy-assistedsurgery J Am Coll Surg 2008206138ndash143

58 Pugliese R Maggioni D Sansonna F et al Outcomes and survivalafter laparoscopic gastrectomy for adenocarcinoma Analysis on 65patients operated on by conventional or robot-assisted minimal ac-cess procedures Eur J Surg Oncol 2008 in press

59 Kitano S Shiraishi N Uyama I et al A multicenter study on on-cologic outcome of laparoscopic gastrectomy for early cancer inJapan Ann Surg 200724568ndash72

60 Ryu KW Kim YW Lee JH et al Surgical complications and the riskfactors of laparoscopy-assisted distal gastrectomy in early gastric can-cer Ann Surg Oncol 2008151625ndash1631

61 Lee JH Kim YW Ryu KW et al A phase-II clinical trial of la-paroscopy-assisted distal gastrectomy with D2 lymph node dissectionfor gastric cancer patients Ann Surg Oncol 2007143148ndash3153

62 Song KY Park SM Kim SN Park CH The role of surgery in the treat-ment of recurrent gastric cancer Am J Surg 200819619ndash22

63 Nakajima T Harashima S Hirata M Kajitani T Prognostic andtherapeutic values of peritoneal cytology in gastric cancer ActaCytol 197822225ndash229

64 Abe S Yoshimura H Tabara H et al Curative resection of gastriccancer limitation of peritoneal lavage cytology in predicting theoutcome J Surg Oncol 199559226ndash229

65 Bentrem D Wilton A Mazumdar M et al The value of peritonealcytology as a preoperative predictor in patients with gastric carci-noma undergoing a curative resection Ann Surg Oncol 200512347ndash353

66 Kim MM Mansfield PF Das P et al Chemoradiation therapy for po-tentially resectable gastric cancer clinical outcomes among patientswho do not undergo planned surgery Int J Radiat Oncol Biol Phys200871167ndash172

67 Bando E Yonemura Y Endou Y et al Immunohistochemical studyof MT-MMP tissue status in gastric carcinoma and correlation withsurvival analyzed by univariate and multivariate analysis Oncol Rep199851483ndash1488

68 Burke EC Karpeh MS Jr Conlon KC Brennan MF Peritoneal lavagecytology in gastric cancer an independent predictor of outcomeAnn Surg Oncol 19985411ndash415

69 Asao T Fukuda T Yazawa S Nagamachi Y Carcinoembryonic anti-gen levels in peritoneal washings can predict peritoneal recurrenceafter curative resection of gastric cancer Cancer 19916844ndash47

70 Nishiyama M Takashima I Tanaka T et al Carcinoembryonic anti-gen levels in the peritoneal cavity useful guide to peritoneal recur-rence and prognosis for gastric cancer World J Surg 199519133ndash137discussion 137

71 Kodera Y Nakanishi H Ito S et al Quantitative detection of dissem-inated free cancer cells in peritoneal washes with real-time reversetranscriptase-polymerase chain reaction a sensitive predictor of out-come for patients with gastric carcinoma Ann Surg 2002235499ndash506

72 Katsuragi K Yashiro M Sawada T et al Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavagefluid of gastric cancer patients who underwent a curative R0 resec-tion Br J Cancer 200797550ndash556

73 Saidi RF ReMine SG Dudrick PS Hanna NN Is there a role forpalliative gastrectomy in patients with stage IV gastric cancer WorldJ Surg 20063021ndash27

74 Lim S Muhs BE Marcus SG et al Results following resection forstage IV gastric cancer are better outcomes observed in selected pa-tient subgroups J Surg Oncol 200795118ndash122

75 Hartgrink HH Putter H Klein Kranenbarg E et al Value of pallia-tive resection in gastric cancer Br J Surg 2002891438ndash1443

76 Ouchi K Sugawara T Ono H et al Therapeutic significance of pal-liative operations for gastric cancer for survival and quality of life J Surg Oncol 19986941ndash44

77 Lin SZ Tong HF You T et al Palliative gastrectomy and chemother-apy for stage IV gastric cancer J Cancer Res Clin Oncol 2008134187ndash192

78 Fujitani K Yang HK Kurokawa Y et al Randomized controlled trialcomparing gastrectomy plus chemotherapy with chemotherapy alonein advanced gastric cancer with a single non-curable factor JapanClinical Oncology Group Study JCOG 0705 and Korea GastricCancer Association Study KGCA01 Jpn J Clin Oncol 200838504ndash506

79 Linhares E Monteiro M Kesley R et al Major hepatectomy for iso-lated metastases from gastric adenocarcinoma HPB (Oxford)20035235ndash237

80 Cheon SH Rha SY Jeung HC et al Survival benefit of combinedcurative resection of the stomach (D2 resection) and liver in gastriccancer patients with liver metastases Ann Oncol 2008191146ndash1153

81 Koga R Yamamoto J Ohyama S et al Liver resection for metasta-tic gastric cancer experience with 42 patients including eight long-term survivors Jpn J Clin Oncol 200737836ndash842

82 Okano K Maeba T Ishimura K et al Hepatic resection for metasta-tic tumors from gastric cancer Ann Surg 200223586ndash91

83 Shirabe K Wakiyama S Gion T et al Hepatic resection for thetreatment of liver metastases in gastric carcinoma review of the lit-erature HPB (Oxford) 2006889ndash92

84 Ambiru S Miyazaki M Ito H et al Benefits and limits of hepaticresection for gastric metastases Am J Surg 2001181279ndash283

85 Hermans J Bonenkamp JJ Boon MC et al Adjuvant therapy aftercurative resection for gastric cancer meta-analysis of randomizedtrials J Clin Oncol 1993111441ndash1447

86 Mari E Floriani I Tinazzi A et al Efficacy of adjuvant chemother-apy after curative resection for gastric cancer a meta-analysis of




Ly and Sasson

published randomised trials A study of the GISCAD (GruppoItaliano per lo Studio dei Carcinomi dellrsquoApparato Digerente) AnnOncol 200011837ndash843

87 Macdonald JS Smalley SR Benedetti J et al Chemoradiotherapyafter surgery compared with surgery alone for adenocarcinoma ofthe stomach or gastroesophageal junction N Engl J Med 2001345725ndash730

88 Medical Research Council Oesophageal Cancer Working GroupSurgical resection with or without preoperative chemotherapy inoesophageal cancer a randomised controlled trial Lancet 20023591727ndash1733

89 Cunningham D Allum WH Stenning SP et al Perioperativechemotherapy versus surgery alone for resectable gastroesophagealcancer N Engl J Med 200635511ndash20

90 Kunisaki C Takahashi M Makino H et al The influence of stagemigration on the comparison of surgical outcomes between D2 gas-trectomy and D3 gastrectomy (para-aortic lymph node dissection) amulti-institutional retrospective study Am J Surg 2008196358ndash363

91 Ajani JA Barthel JS Bekaii-Saab T et al NCCN Clinical PracticeGuidelines in Oncology Gastric Cancer Version 12009 Availableat httpwwwnccnorgprofessionalsphysician_glsPDFgastricpdfAccessed 23 September 2008




Ly and Sasson

Metabolic imaging with PET using 18F-fluo-rodeoxyglucose is used in various malignancies butits role in gastric cancer still must be determinedAlthough PET is 94 sensitive in detecting gastriccancer7 it was found to be less accurate than spiral CT in staging locoregional involvement but betterat diagnosing distant metastases8ndash10 However PETscan detected 5 of 40 (15) positive nodes missed by CT

In a small series of patients (N = 68) PET scanadded diagnostic value in 15 upstaging 6 anddownstaging 97 A meta-analysis comparing PETultrasound CT and MRI determined that PET scan was the most sensitive imaging modality for

detecting hepatic metastases11 PET may also be useful in determining therapeutic response tochemotherapy Ott et al12 found that tumors that responded metabolically on PET correlatedhighly with histopathologic response and betterpatient survival Therefore PET scan should beused in selected cases such as locally advancedtumors in which the metastatic potential is highor in cases for which neoadjuvant treatment is be-ing considered

Patients are deemed resectable if they are med-ically fit have limited involvement of contiguousstructures and have no evidence of distant metas-tases With locally advanced tumors the tail of the


Table 1 Salient PointsTopics Highlights

Diagnostic studies bull History and physical examinationbull Endoscopy and biopsybull CT scan of the abdomenbull Endoscopic ultrasound for potentially resectable diseasebull PET scan helpful in advanced disease with high risk for metastasis and for patients

being evaluated for chemotherapeutic responsebull Diagnosticstaging laparoscopy for patients undergoing neoadjuvant therapy

Surgical resection bull Main principle of surgical oncology is microscopically negative marginsbull Adequate nodal samplings

Lymphadenectomy bull Japanese institutions are performing a D2 for early gastric cancer and a D34 (para-aortic lymph node dissection) for advanced but resectable disease90

bull Western societies (Dutch trial32) found a D1+ is adequate D2 or above has higher morbidity but no significant benefit

bull NCCN guidelines91 recommended at least 15 nodes be examined

J-pouch reconstruction bull Decrease intestinal transit timebull Better quality of life assessments in postoperative months 30-60 with no significance

lt 30 months or gt 60 months

Laparoscopic surgery bull Less invasivebull Risks for port site recurrence and vascular injurybull Feasible for early gastric cancers

Peritoneal lavage bull Additional prognostic informationbull Low yieldbull Further clinical studies needed

Recurrent disease bull Improved survival if an R0 was achievedpalliative gastrectomy bull Patient is medically fit

bull Usual indication obstruction or excessive bleeding

Hepatic metastasectomy bull Improved survival if an R0 was achieved and for patients with metachronous diseasebull Limited hepatic involvement adequate functional residual liver volume

and no extrahepatic disease

Adjuvant therapy bull MacDonald trial87 (SWOG-9008 INT-0116 RTOG-9018 NCCTG-90-41-51 ECOG-6290 CALGB 9195) showed survival benefit with adjuvant chemoradiation

bull Cunningham et al89 (MAGIC trial) showed survival benefit with perioperative chemotherapy

bull Multidisciplinary management is recommended


















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