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- 1. Management of GastricCancer By; Yoseph Temesgen(GSR4) MODERATOR : Dr. Dhabessa,ASSISTANT PROF. SURGERY GI Fellow
- 2. Outline Introduction Epidemiology Clinical presentation Diagnostic workups and staging Treatment Gastric GIST, Lymphoma
- 3. INTRODUCTION :Epidemiology 1. PRIMARYMALIGNANT NEOPLASMS OF THE STOMACH The three most common neoplasms are: Other rare malignancies: 2. SECONDARY INVOLVEMENT: heamatogenous, adjacent organs invade the stomach by direct extension or by peritoneal seeding 5th most common cancer in the world and the 3rd leading cause of Ca death Sex and peak age in LES class citizens and Blacks Geographic varaitions Globally there is proximal migration of tumors It has decreased by 2/3 in the past 50yrs & estimated 5-year survival rate is 27%
- 4. Epidemiology • Ethiopia noclear report: hospital studies
- 6. Clinical Presentation • Threeseparate disease • May arise from the d/se • Symptoms are often absent in early stages, and when present are often ignored, missed, or mistaken for another disease process. • Vague discomfort and/or indigestion • Epigastric pain that is constant, non-radiating, and unrelieved by food ingestion. • Dysphagia, outlet obstruction, Chronic GIB with some form of IDA (40%) with melena (ulcerated lesions). • Screening: in pts with dysphagia & dyspepsia
- 7. Signs • palpable abdominalmass and wt loss • Lymphatics and peritoneal spread can present with an enlarged ovary or a mass in the cul-de-sac • Ascites, liver mass • Paraneoplastic syndromes • Mode of cancer spread 1. Direct 2. Lymphatics 3. Hematologic 4.Transperitoneal metastatic site is to the liver, peritoneal surfaces, and non regional or distant lymph nodes, Lung
- 8. Pathology • Dysplasia, superficialtumors and Advanced Gastric CA(Locoregional & Metastatic) • Early Gastric CA: T1a and T1b adenocarcinoma • LN met and several types • Morphology(Bormann): polypoid, fungating, ulcerative, scirrous • Histology: adeno, adenosquamous, SCC, Undiff &others • Lauren and Ming classification
- 9. Diagnostic evaluation andstaging CBC , OFTs, electrolytes, Serum-Albumin and coagulation studies, OBT Tumor markers like CEA, CA-125, CA-19-9, B-HCG A double-contrast UGI barium study • an upper endoscopy and biopsy The combination of CT with EGD has become gold standard diagnostic imaging.
- 10. Staging evaluation Staging investigation:-MULTIDISCIPLINARY • Contrast CT • EUS • Laparoscopy &Peritoneal cytology • PET NB:- NCCN recommendations include the use of diagnostic laparoscopy and peritoneal washings for cytology for all tumors stage IB or higher when resection is considered
- 11. STAGING OF GASTRICCANCER TNM staging system Factors which isn’t reflected well by current TNM system: The location of the primary (cardia Vs distal tumors), Positive Lymph node ratio, Location of L. nodes
- 13. TUMOR MANAGEMENT • Options •Surgery • Chemotherapy • Radiotherapy • Immunotherapy • Three factors should be decided for operable ones • Suitability to undergo resection • Accurate three tool staging • Sequence of treatment
- 15. Multimodality treatment forIB- IIIC: Surgical Treatment The goal of curative surgery All margins should be negative and an adequate lymphadenectomy performed Extent of resection depends on the size and the location of the tumor in the stomach- Intraoperative frozen section • Indicators of unresectability Distant metastases Invasion of a major vascular structure: distal splenic artery Lymph nodes involvement- Celiac LNs
- 16. Gastrectomy • Types – Basedon amount removed • Total • Near total • Subtotal • Partial • Hemigastrectomy • antrectomy distal gastrectomy Standard Vs Non standard Gastrectomy(modified & extended) • Based on reconstruction – Following distal gastrectomy » Billroth 1 » Billroth 2(polya) » Roux-en-Y GJ – Following proximal gastrectomy • Without reservoir » Roux- en –Y » Jejunal and colonic interpositions • With reservoir » Roux- en –Y with pouch » Jejunal interposition with pouch » ileo-cecal pouch
- 17. Extent & indicationsof LND
- 18. D1 vs D2Lymphadenectomy
- 20. Indications of LNDissection D2- Japan D1 & D1+- westerns D2+ – Dissection of No. 10 – Dissection of No. 14v – Dissection of No. 13 – Dissection of No. 16
- 21. Distal Radical SGvs Total Gastrectomy transected at the level of the incisura and Resected organs and Frozen section analysis should be performed before reconstruction Indications of total gastrectomy total gastrectomy or proximal subtotal gastrectomy. Reconstruction: Benefit & risk of each
- 22. Updated Guidelines onspecial areas 1. Vagal Nerve Preservation:PPG 2. Omentectomy: for tumours of T3 or deeper 3. Bursectomy: removing microscopic deposit of omental cavity 4. Hepatic metastasis: 30% 5yr survival 5. Peritoneal cytology: Periop chemo or HIPEC or IV &IP paclitaxel+S-1 6. Periop Nutrition: Prealbumin>22mg/dl 7. GEJ tumors
- 23. • Esophagogastric junction(GEJ)tumors previously used was seiwert classification into three types
- 24. Rx of GEJtumours • Tumours of cardia &GEJ from view pt of lymphatic spreading • Adenocarcinoma of <40mm: lymphadenectomy(stations at distal stomach low) & gastrectomy • Approaches
- 25. Sequence of OperativeProcedures • Supine • Incision :- upper midline, chevron—xiphoid can be resected • Inspect and palpate • General peritoneum • Liver • Kocherization :- for paraaortic LN
- 26. Step 1. Mobilizationof the greater curvature with omentectomy and division of the left gastroepiploic artery Step 2: Infrapyloric mobilization with ligation of the right gastroepiploic vein at its juncture with the middle colic vein and LN dissection • Dissection continued towards pancreas being the lower limit • dissect anterior leaf of mesocolon and pancreatic omentm :- until gastrodoudenal found and Rt GE artery found and ligated
- 27. Step 3 .Suprapyloric mobilization with ligation of the right < gastric vessels near the hepatic artery with LN dissn • Dissn of porta hepatis, CHA, LGA, CA & splenic A
- 28. step4. Transection ofthe duodenum step5. Stomach division
- 29. step6. Reconstruction canbe achieved by a loop gastrojejunostomy (Billroth II anastomosis), constructed by bringing the jejunum up to the gastric pouch
- 30. Total gastrectomy Step 1,2 &3 Step 4. The splenic hilum is carefully dissected Step 5. duodenum divided Step 6. Mobilization of esophageal hiatus is completed by detaching the peritoneal reflection from the diaphragm and divided sharply and stabilized
- 31. Reconstruction Division of smallintestine Standard end-to-side reconstruction, using monofilament absorbable sutures in a single continuous layer.
- 32. Anatomy • Posterior GastricA. • Short gastric A. • Lt gastroepiploic A. • Last part of antrum
- 33. Endoscopic Resection: EMROR ESD For early gastric cancer: Benefits and risks • Standard criteria • Extended criteria
- 34. Endoscopic Curability • eCuraA, eCura B, eCura C • Cura Score 5clinicopathologic factors • Size>3cm, VM1, venous invasion, SM2 and Lymphatic invasion
- 35.
- 36.
- 37. Chemotherapy and radiotherapy Gastric cancer remains a biologically aggressive cancer with high recurrence rates mortality Overall survival & progression free survival in adjuvant & surgery alone • Adjuvant & Neoadjuvant :- strongly advocated despite multiple trials show modest result • Southwest oncology group , Classic trial , MAJIC trial, macdonald protocol • Indications, Standard Criteria for Chemo and benefit
- 38. Mgt of advanceddisease • ?Curative gastrectomy • Palliative chemotherapy • Palliative procedures(local palliation) – Palliative gastrectomy:- reserved for palliation of symptoms(uncontrollable bleeding ,GOO, pain – Surgical bypass – Endoluminal stent – Venting gastrostomy and/or feeding jejunostomy • Palliative radiotherapy :Indications
- 40. Linitus plastica • Raretype of adenocarcinoma and Common in younger patients. • Diffuse involvement whole layer. • On endoscopy: highly folded and nonstretchable stomach seen. • Differenciation from high grade lymphoma is important. • Treatment: Surgery is not usually successful • Chemotherapy may be considered for palliative treatment. 40
- 41. Prognosis and outcome The 5-year survival has increased from 22% • 5-year survival for resected stages • Survival is dependent on pathologic stage (TNM stage) and degree of tumor differentiation and other factors Over expression of HER2
- 42. Surveillance • Nutrition: B12and iron , Supplemental tube feeding • Follow-up • Complete Hx and P/E »Every 3-6 mo for 1-2yr »Every 6-12 mo for 3-5yr »Then annually • Lx studies • Imaging if clinically indicated • Endoscopic evaluation
- 43. Gastrointestinal Stromal Tumor •Originally thought to be a type of SM sarcoma, from ICC • Stomach (50% to 70%) • Variable presentation and clinical course • Most GISTs manifest symptomatically • identified by immunohistochemical staining for the c-kit proto-oncogene (CD117), and for CD34 but not actin & desmin • Types: Epithelial, cellular & Glomus
- 44. Treatment • The mainstayof treatment is complete surgical resection • Endoscopy and EUS at 6- to 12-month intervals for <2cm • Depending on tumor size, options of resection include: wide local excision, Enucleation, sleeve gastrectomy, total gastrectomy, with or without en bloc resection of adjacent organs & LND • Risk stratification based on tumour size & mitotic activity • imatinib (Gleevec) is used as adjuvant , neoadjuvant and palliative therapy atleast for 3yrs Indications for tyrosine kinase inhibitor moderate to high risk for recurrence or metastasis(>3cm or >5mitosis/hpf) after resection of resectable ds, unresectable tumour & metastatic disease Importance in metastatic & adjuvant, 5yr survival 50%
- 45.
- 46. Gastric Lymphoma • Thestomach is the most common site(50%) • The normal stomach devoid of lymphoid tissue • H.pylori & gastritis • Patients often present with vague symptoms,such as epigastric pain, early satiety, and fatigue • Constitutional B symptoms & overt bleeding • usually site is in the gastric antrum
- 47. Treatment • Low Grade,High grade • The role of resection in gastric lymphoma is controversial. • most patients are treated with chemotherapy alone. • CHOP Regimen • indications for surgery; patients with symptomatic recurrence of treatment failure patients who develop complications, such as bleeding, gastric outlet obstruction,or perforation
- 48. Reference 1. SCHWARTZ’S PRINCIPLESOF SURGERY , 10th edition 2. Maingot’s ABDOMINAL OPERATIONS 12th edition 3. Shackelford’s SURGERYof the ALIMENTARY TRACT, 7th edition 4. Uptodate 21.6 5. Master technique in surgery
- 49.
Editor's Notes
- #4 Benign tumors : -Polyp -Leiomyoma -Inflammatory lesions -Heterotopic pancreas
- #5 5th most common world wide and 3rd in mortality the 4th most common cancer in men and 7th in women
- #7 CLINICAL FEATURES — Weight loss and persistent abdominal pain are the most common symptoms at initial diagnosis ( table 1 ) [ 1 ]. Weight loss usually results from insufficient caloric intake rather than increased catabolism and may be attributable to anorexia, nausea, abdominal pain, early satiety, and/or dysphagia. When present, abdominal pain tends to be epigastric, vague and mild early in the disease but more severe and constant as the disease progresses. Dysphagia is a common presenting symptom in patients with cancers arising in the proximal stomach ( figure 1 ) or at the esophagogastric junction. Patients may also present with nausea or early satiety from the tumor mass or in cases of an aggressive form of diffuse-type gastric cancer called linitis plastica, from poor distensibility of the stomach. They may also present with a gastric outlet obstruction from an advanced distal tumor. Occult gastrointestinal bleeding with or without iron deficiency anemia is not uncommon, while overt bleeding (ie, melena or hematemesis) is seen in less than 20 percent of cases. The presence of a palpable abdominal mass is the most common physical finding and generally indicates long-standing, advanced disease [ 1 ]. A pseudoachalasia syndrome may occur as the result of involvement of Auerbach's plexus due to local extension or to malignant obstruction near the gastroesophageal junction. For this reason, gastric cancer needs to be considered in the differential diagnosis for older patients presenting with achalasia [ 2 ]. Approximately 25 percent of patients have a history of gastric ulcer. All gastric ulcers should be followed to complete healing, and those that do not heal should undergo resection Te symptoms of gastric cancer are generally nonspecifc and contribute to its frequently advanced stage at the time of diagnosis. Symptoms include epigastric pain, early satiety, and weight loss. Tese symptoms are frequently mistaken for more common benign causes of dyspepsia including PUD and gastritis. Te pain associated with gastric cancer tends to be constant and nonradiating and is generally not relieved by eating. More advanced lesions may manifest with either obstruction or dysphagia depending on the location of the tumor. Some degree of GI bleeding is common, with 40% of patients having some form of anemia and 15% having frank hematemesis
- #8 Signs of tumor extension or spread — The signs and symptoms described above are those most commonly seen at initial presentation of gastric cancer. More unusual presentations, related to the propensity of gastric cancer to spread by direct extension through the gastric wall, can also alert the clinician to the diagnosis. As an example, feculent emesis or passage of recently ingested material in the stool can be seen with malignant gastrocolic fistula, although this is quite rare. More commonly, colonic obstruction may occur. Patients may also present with signs or symptoms of distant metastatic disease. The most common metastatic distribution is to the liver, peritoneal surfaces, and nonregional or distant lymph nodes. Less commonly, ovaries, central nervous system, bone, pulmonary or soft tissue metastases occur Since gastric cancer can spread via lymphatics, the physical examination may reveal a left supraclavicular adenopathy (a Virchow's node [ 3 ]) which is the most common physical examination finding of metastatic disease, a periumbilical nodule (Sister Mary Joseph's node [ 4 ]), or a left axillary node (Irish node). Peritoneal spread can present with an enlarged ovary (Krukenberg's tumor [ 5 ]) or a mass in the cul-de-sac on rectal examination (Blumer's shelf [ 6 ]). However, there are patients with ovarian metastasis without other peritoneal disease. Ascites can also be the first indication of peritoneal carcinomatosis. A palpable liver mass can indicate metastases, although metastatic disease to the liver is often multifocal or diffuse. Liver involvement is often, but not always, associated with an elevation in the serum alkaline phosphatase concentration. Jaundice or clinical evidence of liver failure is seen in the preterminal stages of metastatic disease [ 7 ].
- #10 Imaging ….(include the chest if the tumor is suspected to be more proximally located) Although many tumor markers may be associated with gastric cancer (CEA, CA-125, CA 19-9, β-HCG), none are sensitive enough to stand alone as indicators of the presence of the disease. However, the combination of the markers may be useful in determining disease burden and if many are elevated simultaneously, they can be used as an indicator of aggressive forms of the cancer Upper GI barium study is superior to endoscopy in diagnosing diffuse type of gastric ca , giving leather bottle appearance of the stomach.
- #11 On initial diagnostic endoscopy, if a suspicious mass or ulcer is encountered in the stomach, it is essential to obtain adequate tissue to confirm the correct diagnosis histologically. Multiple biopsy specimens (six to eight) should be taken of different areas of the lesion using endoscopic biopsy forceps A single biopsy specimen results in a diagnostic sensitivity of 70%, whereas seven biopsy specimens increases this yield to 98% Small lesions (<2 cm in diameter) can be resected at the time of initial diagnostic endoscopy using endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) techniques This resection can provide a more complete specimen to aid the pathologist in obtaining an accurate diagnosis and can potentially be curative for early-stage cancers, obviating the need for any further invasive surgical intervention The overall accuracy of EUS has been reported to be 85% for T stage and 80% for N stage; however, these studies considered accuracy retrospectively and not the predictive accuracy of EUS, and most were analyses of data obtained from single institutions However, it showed improved accuracy when T and N stages were grouped together to differentiate high-risk versus low-risk disease, defined by the presence of any serosa (T3/T4) involvement or any nodal disease (>N0) When this classification system was used, the positive predictive value of EUS to identify advanced disease was 76%, and the negative predictive value to identify low-risk disease was 91% From a prognostic and treatment standpoint, this classification may be more clinically relevant because an EUS finding indicative of advanced disease strongly correlates with decreased resect ability and poorer disease-specific survival
- #12 Before 1997, N stage was determined by the anatomic location of the nodes with respect to the primary tumor, rather than the absolute number of nodes This staging, based on anatomy, was intimately related to the D1 versus D2 anatomic lymphadenectomy debate The revised system does not differentiate among the locations of positive nodes In the current staging system, a minimum of 15 nodes must be evaluated for accurate staging Some experts have suggested that other factors be included in the T and N assessment, such as the location of the| primary (cardia compared with distal tumors) because this may independently predict survival and emphasis on the percentage of positive nodes (lymph node ratio) rather than the number of positive nodes However, the current AJCC staging system does not reflect these factor Once gastric cancer has been diagnosed, the presence of metastatic disease determines the first branch point in the treatment algorithm: is the patient’s specific cancer amenable to surgical resection or should palliative measures be the primary guiding principle? Generally, those patients with stage I to III or M0 disease can be placed in the surgical resection group, and those with any nodal metastases or stage IV disease considered for palliative therapy As mentioned earlier, EGD is the modality of choice for the diagnosis of gastric cancer owing to the ability to obtain tissue samples for histologic examination Usually, multiple biopsies are taken and the extent of lumen involvement can be ascertained quite readily. Some circumstances, such as linitis plastica, present more of a challenge when EGD is used for biopsies, because the nature of the cancer makes the tissue less pliable However, EGD can provide other methods of dealing with gastric tumors such as laser ablation and stenting (for proximal lesions) that have proven to be useful in select patients When considering nodal status, recent advances in endoscopic ultrasound (EUS) have allowed practitioners to evaluate the depth of the primary lesion as well as perigastric nodal involvement at the time of upper endoscopy to further guide management decisions Techniques such as fine-needle sampling of nodes is becoming more commonplace, but is still not available in many areas. Not all facilities are equipped to provide these services, however, and even at hospitals with EUS capabilities it remains dependent on operator experience and skill With regard to imaging patients with suspected disease, CT remains the primary mode of evaluating location and possible nodal involvement. Intravenous contrast aids in the identification of solid-organ metastases and lymph node spread, but is variable in accuracy with regard to the latter Magnetic resonance imaging (MRI) has been used recently with some success to diagnose and more accurately stage gastric cancer, but it remains cost prohibitive and can be affected by motion artifact Positron emission tomography (PET) has also been used in the assessment of possible metastatic disease, as gastric adenocarcinoma is usually PET avid. Its use in other forms of cancer makes it extremely appealing in patients who may have advanced disease and can be especially helpful for evaluating recurrence Diagnostic laparoscopy has also proven itself worthy in assessing metastatic disease, as it can more readily identify small lesions not seen by other imaging. It has been reported that approximately 30% of patients are upstaged after diagnostic laparoscopy,18 and potentially spared an extensive and painful laparotomy in favor of palliative measures. The diagnostic yield of laparoscopy can be enhanced through cytologic washings obtained during the procedure. The presence of malignant cells in abdominal washings can be of great prognostic significance,19 with the mean survival of patients with negative washings being greater than 6 times that of those with positive cytologic findings.
- #16 Thus, all margins (proximal, distal, and radial) should be negative and an adequate lymphadenectomy performed Generally, the surgeon strives for a grossly negative margin of at least 5 cm Some gastric tumors, particularly the diffuse variety, are quite infiltrative and tumor cells can extend well beyond the tumor mass; thus, gross margins beyond 5 cm may be desirable Frozen section confirmation of negative margins is important when performing operation for cure, but it is less important in patients with nodal metastases beyond the N1 nodal basin nodal basin It should be strongly emphasized that many patients with positive lymph nodes are cured by adequate surgery. It should also be stressed that often lymph nodes that appear to be grossly involved with tumor turn out to be benign or reactive on pathologic examination. More than 15 resected lymph nodes are required for adequate staging Therapeutic nihilism should be avoided and, in the low-risk patient, an aggressive attempt to resect all tumor should be made. The primary tumor may be resected en bloc with adjacent involved organs (e.g., distal pancreas, transverse colon, or spleen) during the course of curative gastrectomy Palliative gastrectomy may be indicated in some patients with obviously incurable disease, but most patients presenting with stage IV gastric cancer can be managed without major operation
- #19 Given the apparent impact of D2 lymphadenectomy on disease specific survival, most major cancer centers are performing a D2 as compared to a D1 dissection Treatment guidelines published by the National Comprehensive Cancer Network recommend that D2 lymph node dissection is preferred over a D1 dissection The arguments in favor of extended lymphadenectomy (ie, D2 or D3 versus D1) are that removing a larger number of nodes more accurately stages disease extent and that failure to remove these nodes leaves behind disease (which would be a potentially fatal event) in as many as one-third of patients [ 36-38 ]. A consequence of more accurate staging is to minimize stage migration (the “Okie phenomenon”, as described by Will Rodgers) [ 38,39 ]. The resulting improvement in stage-specific survival may explain, in part, the better results in Asian patients. The influence of total lymph node count on stage-specific survival was studied in a series of 3814 patients undergoing gastrectomy for T1-3 N0-1 (classified according to the 1997 AJCC gastric cancer staging system and reported to the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2000) [ 40 ]. For every stage subgroup (T1/2N0, T1/2N1, T3N0, T3N1), survival was significantly better as more nodes were examined ( table 3 ). Although cut point analysis revealed the greatest survival difference when 10 lymph nodes were examined, there were significant survival differences for cut points up to 40 nodes examined, always in favor of a greater number of nodes in the specimen. There are two main arguments against the routine use of an extended lymphadenectomy: the higher associated morbidity and mortality (particularly if splenectomy is performed in order to achieve extended lymphadenectomy) and the lack of a survival benefit for extended lymphadenectomy in most large randomized trials. Randomized trials and meta-analyses — Although retrospective reports suggest that extended lymphadenectomy improves survival [ 41-43 ], multiple prospective randomized trials both in Asian and Western populations have failed to show an overall survival benefit with D2 versus D1 lymphadenectomy [ 44-46 ] or with D3 compared to D2 lymphadenectomy [ 35,47-49 ]. The range of findings can be illustrated by the three largest trials. D1 versus D2 dissection MRC trial – The Medical Research Council (MRC) randomly assigned 400 patients undergoing potentially curative resection to a D1 or a D2 lymphadenectomy [ 45 ]. Postoperative morbidity was significantly greater in the D2 group (46 versus 28 percent), as was operative mortality (13 versus 6 percent). The excess morbidity and mortality were clearly associated with the use of splenectomy and distal pancreatectomy to achieve complete node dissection. In a later follow-up, five-year survival rates were no better for patients undergoing D2 compared to D1 dissection (33 versus 35 percent) [ 50 ]. Dutch trial – The largest randomized trial came from the Dutch Gastric Cancer Group and compared D1 with D2 lymphadenectomy in 711 patients who were treated with curative intent [ 46,51 ]. This trial relied heavily upon input from a Japanese surgeon, who trained eleven Dutch surgeons in the technique of radical lymph node dissection and monitored the operative procedures. Despite these efforts to maintain quality control of the surgical procedures, both under removal and over removal of required nodal stations occurred, somewhat blurring the distinction between the groups. As was shown in the MRC trial, both postoperative morbidity (43 versus 25 percent) and mortality (10 versus 4 percent) were higher in the D2 group. Moreover, a statistically significant survival advantage in the radical dissection group was not observed, both in the initial report [ 46 ] and with longer follow-up [ 51,52 ], despite a significantly lower risk of recurrence. This was attributed to the detrimental impact of increased operative mortality in this group. The conclusion of the Dutch trial (and its accompanying editorial [ 53 ]) was that D2 lymph node dissection could not be routinely recommended. Many clinicians consider that both the Dutch and the MRC trials are flawed. The design of the Dutch trial was based upon the assumption that radical lymph node dissection would increase the survival rate from 20 to 32 percent, likely an overestimation of benefit. Furthermore, 40 percent of enrolled patients had early gastric cancer, an unexpectedly high proportion that was not anticipated when the trial was designed. Moreover, both the MRC and the Dutch studies were relatively underpowered for the group of patients most likely to benefit from the extended dissection. If the proportion of patients with N2 disease is approximately 30 percent, and only approximately one-fourth of these patients survive five years after a potentially curative D2 lymphadenectomy, less than 8 percent of patients benefit long-term (0.25 x 0.30). These results indicate that one additional life might be saved for every 13 patients undergoing a D2 dissection and that much larger sample sizes are needed [ 37 ]. Thus, the benefit of D2 versus D1 dissection (particularly using safer spleen-preserving D2 dissection techniques) remains controversial. The Dutch trial has been updated with 15-year follow-up [ 52 ]. The survival curves have continued to separate, although the difference in overall survival is still not statistically significant (22 versus 28 percent in the D1 and D2 arms, respectively, p=0.34). However, the gastric cancer-related death rate is significantly higher in the D1 arm (48 versus 37 percent) while death rates due to other causes were not different. This supports the concept that if the D2 dissection can be done with low operative mortality, similar to that of a D1 dissection (as occurs in high volume centers), there will be a positive survival impact. This mirrors the conclusion of the latest Dutch trial paper, which is that D2 dissection is recommended in patients with potentially curable gastric cancer. D2 versus D3 dissection JCOG trial 9501 – The multicenter Japan Clinical Oncology Group (JCOG) study 9501 randomly assigned 523 patients to D2 versus D3 (D2 + PAND) dissection. The overall perioperative complication rate in the D3 group was significantly higher (28.1 versus 20.9 percent), although there were no differences in major complications (anastomotic leak, pancreatic fistula, abdominal abscess, pneumonia) and perioperative mortality was very low (0.8 percent) in both groups [ 47 ]. Five-year recurrence-free (approximately 63 percent in both groups) and overall survival (70 versus 69 percent) were no better after extended lymphadenectomy [ 35 ]. One of the confounding issues with the JCOG trial is that in subgroup analysis, patients with node-negative disease fared significantly better with the more aggressive D2 operation than with D1 lymphadenectomy. Conversely, patients who were node-positive fared significantly better with a D1 lymphadenectomy than with more D2aggressive surgery. The reasons for these results counterintuitive results are unclear. Nevertheless, the high survival rate in both groups is notable in view of the fact that over 60 percent of both groups had positive nodes. These data underscore the marked differences in outcome between gastric cancers arising in Western and Asian populations. (See 'Prognosis' below.) Data from the JCOG trial as well as those from other groups [ 47,54 ] suggest that a D2 dissection can be performed safely with a perioperative mortality rate that is under 2 percent. Meta-analysis – A meta-analysis of the JCOG trial and two other smaller randomized trials of D2 versus D3 (with PAND) dissection [ 48,49 ] concluded that resection of the paraaortic nodes was inferior to a D2 dissection in terms of safety and without any survival benefit [ 55 ]. Thus, paraaortic lymphadenectomy should not be considered a routine practice for surgical treatment of gastric cancer. The importance of surgeon and institutional expertise — The first United States study to assess outcome using Japanese lymphadenectomy criteria was performed using patients in a randomized trial of adjuvant therapy and provided a sobering view of current surgical practice in patients with resectable gastric cancer [ 56 ]. In this randomized trial (Intergroup trial 0116) examining the utility of adjuvant chemoradiotherapy, in 556 patients with potentially resectable gastric cancer, 54 percent underwent less than a D1 lymphadenectomy, while D1 or ≥D2 procedures were performed in 36 and 10 percent, respectively. Others have shown that fewer than one-third of American patients undergoing gastric cancer surgery had 15 or more lymph nodes removed/examined, even in academic and high-volume hospitals [ 57-59 ]. (See "Adjuvant and neoadjuvant treatment of gastric cancer" .) The importance of extent of lymphadenectomy on outcome was demonstrated when patients were stratified according to the Murayama Index [MI], a computer-based model that predicts the likelihood of disease in the regional nodal stations left undissected by the surgeon [ 60,61 ]. Median survival had not been reached in patients with a low MI, whereas it was only 27 months for cases with MI ≥5. In view of these data, we believe that aggressive nodal dissection should only be performed in selected centers where surgeons have demonstrated acceptably low operative morbidity and mortality rates. Our own experience, as well as that at Memorial Sloan Kettering and in Japan, suggests that mortality rates under 2 percent should be expected at centers with higher patient volume [ 47,54 ]. Unfortunately, such surgical expertise is limited in the United States, and data from the American College of Surgeons suggest that procedure-related mortality is significantly higher in American series [ 3 ]. An examination of mortality rates for gastrectomy in the US has demonstrated that among patients with gastric tumors who presented to more than 700 hospitals between 1982 and 1987, the average perioperative mortality rate was 7.2 percent. Not surprisingly, variability in perioperative mortality appears dependent upon the volume of gastrectomies at individual institutions. In one series, perioperative mortality rates ranged from 8.7 to 13 percent at very high volume (over 21 procedures per year) and very low volume hospitals (fewer than 5 procedures per year), respectively [ 62 ]. The adjusted odds ratio for death at the highest compared to the lowest volume institutions was 0.72 (95% CI 0.63-0.83). This was also shown in a more recent study conducted in the state of Texas over a three-year period (1999 to 2001) that examined gastrectomies performed at all non-federal hospitals [ 63 ]. Over 1800 resections were performed in 214 hospitals, with high volume centers performing more than 15 resections per year and low volume centers fewer than three. Hospital mortality ranged from 5.2 to 6.2 percent in the low and intermediate hospitals, respectively, and it was 1.1 percent at the high volume centers. Even with a relatively low cutoff of only 15 resections per year for high volume centers, there were only two high volume centers in the state, underscoring the need for regionalization of this specialized surgery. The impact of hospital volume on long-term disease-free or overall survival is less clear [ 64 ].
- #22 The proximal stomach is transected at the level of the incisura at a margin of at least 6 cm because studies have documented tumor spread as far as 5cm laterally from the primary tumor, although some experts indicate that a 4-cm margin is adequate The possibility of recurrence in the tumor bed (duodenal suture line and surface of the pancreas) suggests a Billroth II reconstruction rather than a Billroth I, which would result in less risk of GOO 2ry to tumor recurrence If the patient is left with a small area of stomach proximal to the area of resection, a Roux-en-reconstruction should be performed to reduce the risk of alkaline reflux esophagitis Organs resected: Distal 75% of stomach 2 cm of duodenum Greater & lesser omentum Ligation of R & L gastric artery and gastroepiploic vesels Billroth II gastojejunostomy
- #34 To avoid undertreating patients, several studies have sought to identify risk factors for harboring lymph node metastases Lymphatic vessel invasion, histologic ulceration of the tumor, and larger size (≥30 mm) were independent risk factors for regional lymph node metastasis. Patients without any of these risk factors had only a 0.36% chance of having lymph node metastases Any of these listed findings on initial biopsy or during endoscopic resection is an indication for gastrectomy with lymph node dissection A Japanese study of 1196 patients with intramucosal gastric cancer without known lymph node disease who underwent resection found, in multivariate analysis, that lymphatic vessel invasion, histologic ulceration of the tumor, and larger size (≥30 mm) were independent risk factors for regional lymph node metastasis
- #36 Endoscopic mucosal resection by strip biopsy: Saline is injected into the submucosal layer, and the area is elevated (1). The top of the mound is pulled upward with forceps, and the snare is placed at the base of the lesion (2 and 3). Electrosurgical current is applied through the snare to resect the mucosa, and the lesion is removed (4). Endoscopic resection can be performed using one of two techniques: EMR or ESD The basic principle for EMR involves elevating the tumor using a saline injection and then encircling the affected mucosa using a snare device to excise it with electrocautery Perforation rates are low, and bleeding rates are approximately 15%; these can generally be controlled without the need for further intervention
- #37 Procedure of endoscopic submucosal dissection. A, A type IIa+IIc early gastric cancer was located at the lesser curvature side of the antrum. B, Indigo carmine dye was sprayed around the lesion to define the margin accurately. C, Marking dots were made circumferentially at approximately 5 mm lateral to the margin of the lesion. D, After a submucosal injection of saline with epinephrine mixed with indigo carmine, a circumferential mucosal incision was performed outside the marking dots to separate the lesion from the surrounding non-neoplastic mucosa. E and F, After an additional submucosal injection, the submucosal connective tissue just beneath the lesion was directly dissected using an electrosurgical knife instead of using a snare. G, The lesion was completely resected, and the consequent artificial ulcer was seen. H, The resected specimen with a central early gastric cancer.
- #42 In breast cancer, overexpression of HER2 has been reported in 15%-25% and is well recognized as one of the unfavorable prognostic factors However, the development of molecular targeted agents such as trastuzumab has improved the survival of HER2 positive patients Likewise, recently in gastric cancer, HER2 overexpression has been reported in 13% -30% of patients According to the result of large clinical trial, Immunohistochemistry (IHC) staining of HER2 has become the important examination for recurrent or metastatic gastric cancer to decide the treatment strategy In general, the actuarial 5-year survival for resected gastric adenocarcinoma stages I, II, and III is about 75%, 50%, and 25%, respectively
- #44 They are rarely associated with familial syndromes such as GISTparaganglioma syndrome (Carney triad), neurofibromatosis and von Hippel-Lindau disease, but most develop de novo.
- #45 Recurrence rates are approximately 40%, and most patients who experience recurrence demonstrate metastasis to the liver, with one third having only isolated local recurrence. Recurrence can occur 20 years later, and long-term follow-up is warranted. Long-term disease-free survival is approximately 50%, with 20% to 80% of patients dying of their disease. Although there are no dichotomous criteria that are able to define benign versus malignant lesions histologically, the most important risk factors for malignancy are tumor size larger than 10 cm and more than five mitoses/50 high-power fields (HPF). Based on a long-term follow-up study of 1700 patients with gastric GISTs, guidelines for assessing malignant potential based on the combination of these two factors have been developed
- #47 lymphoma (3%), and mantle cell and follicular lymphomas (each <1%). Diffuse large B cell lymphomas are generally primary lesions; however, they may also occur from progression of less aggressive lymphomas, such as chronic lymphocytic leukemia–small lymphocytic lymphoma, follicular lymphoma, and MALT lymphoma. Immunodeficiencies and H. pylori infection are risk factors for the development of primary diffuse large B cell lymphoma. Burkitt lymphomas of the stomach are associated with Epstein- Barr virus infections, as they are in other sites. Burkitt lymphoma is very aggressive and tends to affect younger patients than other types of gastric lymphomas. Burkitt lymphoma is usually found in the cardia or body of the stomach as opposed to the antrum. Evaluation Endoscopy generally reveals nonspecific gastritis or gastric ulcerations. Occasionally, a submucosal growth pattern renders endoscopic biopsies nondiagnostic. EUS is useful to determine the depth of gastric wall invasion, specifically to identify patients at risk for perforation secondary to full-thickness involvement of the gastric wall. Evidence of distant disease should be sought through upper airway examination, bone marrow biopsy, and CT of the chest and abdomen to detect lymphadenopathy. Biopsies should be performed of any enlarged lymph nodes. Histologic H. pyloritesting should be performed and, if negative, confirmed by serology. Staging The best staging system is controversial. When possible, the TNM staging system should be used (using the criteria proposed for gastric carcinoma). Several other staging systems for primary gastric non-Hodgkin lymphoma are available
- #48 The diagnosis of lymphoma discovered unexpectedly at surgery can be confirmed by frozen section. Also, fresh tissue should be sent for fluorescence-activated cell sorting, immunohistochemistry, and genetic analysis. Consideration should be given to bone marrow aspiration at the time of surgery. If isolated stage IE or IIE lymphoma is encountered, surgical removal of all gross disease is ideal. Patients with disseminated lymphoma cannot be cured surgically, and the operation should focus on obtaining enough tissue for diagnosis and the repair of perforations. A prospective randomized study evaluated several treatment strategies—surgical resection, resection plus radiation, resection plus chemotherapy, chemotherapy alone—in patients with early-stage (stage IE or IIE) disease.43 The addition of chemotherapy was essential, with the surgery plus chemotherapy and chemotherapy-alone groups having significantly higher overall survival than the surgery-alone and surgery plus