17.02.2016

Standard treatment of gastric cancer

Management of gastric cancer relies primarily on surgical resection of the involved stomach, with reconstruction to preserve intestinal continuity, as resection provides the only chance for cure. The objectives of operative treatment for potentially curable gastric cancers are confirmation of resectability, performance of a complete resection, facilitation of appropriate pathologic staging, and reestablishment of GI continuity and function. Improved long-term survival rates for Japanese patients had been attributed to the extended lymphadenectomies routinely performed in this country. Initial data in two European randomized trials showed no significant differences in overall long-term survival between D1 and D2 dissection groups.
Prompted by the promising results and acceptable toxicity of preoperative (neoadjuvant) chemoradiation therapy in other parts of the GI tract (eg, esophagus, rectum), there is growing interest in neoadjuvant therapy for gastric cancer. The MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) trial investigated perioperative treatment with epirubicin, cisplatin, and continuous 5-fluorouracil (5-FU) infusion (ECF) vs surgery alone, demonstrating improvements in progression-free and overall survival rates with the addition of chemotherapy.
The 5-year survival rate after “curative resection” for gastric cancer is only between 30% and 40% (Table 2). Locoregional recurrence as a component of failure is common in patients undergoing curative resection for gastric cancer. Chemotherapy alone as a surgical postoperative adjunct does not have a defined role in the United States. Neoadjuvant chemoradiation has also been explored as a way to improve tolerability of chemoradiation and to improve resectability and pathologic response rates compared with chemotherapy. Patients with T3-T4 any N M0 tumors are at highest risk of locoregional recurrence after potentially curative surgery (surgery in which all macroscopic tumor has been resected with no evidence of metastatic disease) for gastric cancer. In the North American Intergroup trial (INT-0116) previously mentioned in the section on “Adjuvant therapy,” patients were randomized to receive chemoradiation therapy or observation following resection of stages IB-IV (M0) adenocarcinoma of the stomach. Despite this trial, significant controversy regarding the need for adjuvant treatment persists and is perhaps growing.
Newer radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT) and advanced image guidance, have been explored as a way to reduce the toxicity and improve accuracy of radiation treatments. A recent retrospective study from Korea evaluated chemoradiation compared with observation in patients who underwent a D2 dissection. Studies by the CALGB and other groups do not support that intensification of therapy with ECF above that delivered with 5-FU alone in INT0116 will improve disease-free or overall survival.
Imatinib mesylate (Gleevec) given for 3 years or longer now represents standard of care in the postoperative setting, for selected GIST patients.
In the Scandinavian Sarcoma Group Trial XVIII, reported in JAMA in 2012, patients with resected GISTs deemed to be at high risk of recurrence were randomized to imatinib mesylate, at 400 mg per day, for 1 vs 3 years.
He showed that about 1.1 liter of fresh cabbage juice a day, helps alleviate the pain and treat the gastric(stomach) ulcers,which is successful and better than standard therapies. One if the benefits cabbage provides strengthening the resistance of stomach mucosa against acid attacks. In fact, these compounds stimulate cells form a thin barrier given the role of a shelter, protecting them from acid attacks. During the treatment, microscopic images of cells experienced extensive changes, proving that cabbage juice speeds up mucus activity which rebuilds damaged cells, leading procedure to full recovery. So, prepare some cabbage juice or prepare cabbage and serve it as a fresh salad for your healthy lunch!
You Will Never Hear This From Your Doctor: How To Cure Your Thyroid Gland With Just Two Ingredients! This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractGastric cancer is one of the most common causes of cancer-related death worldwide. Radiotherapy and chemotherapy now have better-defined roles as adjuncts to surgery and in patients with unresectable tumors. Laparoscopy has emerged as an excellent tool to assess the extent of disease and resectability before the surgeon performs an open laparotomy. The extent of lymph node resection, including the number of nodes removed at the time of gastrectomy, continues to be controversial. Because the improvement in survival after gastrectomy during recent decades was usually associated with the performance of extended lymph node dissections (D2 dissections or greater), this practice appeared to be sensible if performed with acceptable complication rates. After distal gastrectomy, Billroth I gastroduodenostomy or, more commonly, Billroth II gastrojejunostomy methods are acceptable for reconstruction. Neoadjuvant treatment may be performed in an attempt to convert an initially unresectable cancer to resectable status (so-called conversion therapy), or it may be used in advanced but resectable disease felt to be at high risk for recurrence following surgery alone. Treatment failure stems from a combination of local or regional recurrence and distant metastases. Radiotherapy can decrease the rate of locoregional failure but has not been shown to improve survival as a single postoperative modality. Individual randomized trials of chemotherapy plus surgery vs resection alone have mostly not demonstrated a definite survival advantage, with the possible exception of patients with widespread nodal involvement and older patients, who may do better with chemotherapy.
A phase III randomized trial suggested that neoadjuvant treatment with chemotherapy and radiation provides superior pathologic outcomes compared with neoadjuvant chemotherapy.
Even patients with node-negative disease (T3 N0) have a gastric cancer-related mortality of about 50% within 5 years.
Chemoradiation therapy following resection of these high-risk patients significantly improved both disease-free and overall survival rates.
Many studies support the contention that aggressive, formal D2 resection may obviate the need for adjuvant treatment in many cases.
These techniques may be especially helpful in reducing small bowel and kidney damage during chemoradiation, although data from large series are not yet available to confirm these results from small series.
Overall survival in this series was higher for patients who received adjuvant therapy, suggesting that a D2 dissection does not preclude the need for adjuvant therapy. The American College of Surgeons Oncology Group (ACOSOG) Z9001 randomized trial found that 1 year of imatinib mesylate extends recurrence-free survival but not overall survival, compared with placebo following resection of intermediate- or high-risk GIST. Those receiving the drug for a longer period had better 5-year relapse-free (66% vs 48%) and overall (92% vs 82%) survival. The fact that cabbage can help treating ulcer, was proved in the 1950?s, in the attempts of Dr.Garrett Cheney, at the Faculty of Medicine at the University of Stafford. Cabbage contains gefarnate -compound similar to carbenoxolone, a remedy used in ulcers treatments. Indian Central Drug Research Institute healed guinea pigs suffering from ulcer only by using cabbage juice.


Laboratory experiments, proved that cabbage destroys an array of bacteria, including bacteria Pylori, which is considered to be the main cause for stomach ulcer. Surgical resection with lymph node dissection is the only potentially curative therapy for gastric cancer.
Perioperative chemotherapy and chemoradiation therapy remain active areas of current investigation. Laparoscopy adds to the accuracy of preoperative imaging, primarily in cases of peritoneal spread or small liver metastases. Subtotal gastrectomy is preferred over total gastrectomy, because it leads to comparable survival but lower morbidity. Preferably, lymphadenectomy includes the lymphatic chains along the celiac, left gastric, splenic, and hepatic arteries, which allows for more precise lymph node staging. Retrospective data had shown that D2 lymphadenectomy is safe and does not increase morbidity. An update of the randomized Dutch D1D2 trial has demonstrated a significant advantage to D2 dissection at 15 years in terms of deaths from gastric cancer (37% after D2, 48% after D1 dissection, P = .01). Postoperative radiotherapy may be appropriate in patients who are not candidates for chemotherapy.
Meta-analyses of postoperative chemotherapy plus surgery vs resection alone have shown minor reductions in death rates, but no specific regimen can be recommended. Mortality is significantly worse in patients with node-positive disease or in those with incomplete (R1, R2) resection.
Because of the apparent benefit of reducing locoregional recurrences, but not distant recurrences, it is possible that more routine use of D2 lymphadenectomy may modify this recommendation in the future. Other studies and subgroup analyses support the recommendations for adjuvant treatment as concluded in the North American trial. This benefit, however, could be predominantly derived from the systemic treatment component. On the placebo arm, KIT mutation in exon 11 was prognostic for worse recurrence-free survival; patients with rectal primaries receiving imatinib also had poorer outcomes.
More patients getting therapy for a longer period of time had high-grade adverse events, possibly due simply to the prolonged exposure to toxic effects of therapy. However, the appropriate extent of lymph node dissection accompanied by gastrectomy for cancer remains controversial. As a result, morbidity, hospital stay, and costs have been reduced significantly in patients with unresectable lesions. A 5-cm margin of normal stomach appears to be sufficient in proximal and distal resections.
The exact level designation of lymph nodes varies with the site and intragastric location of the primary tumor. Recent population data reviews have linked higher total lymph node numbers (up to 40) to superior survival.
Splenectomy should be avoided unless it is indicated by direct tumor extension, because it significantly increases the rate of complications.
Nonetheless, in resectable patients, perioperative chemotherapy added to surgery is now a standard of care in many parts of the world. A North American Intergroup trial (INT116) randomizing resected patients (stages IB-IV[M0]) to receive chemoradiation with 5-FU plus leucovorin therapy or observation showed significant improvement in median disease-free survival (median 19 vs 30 months) and overall survival (26 vs 35 months) with adjuvant therapy. Alternative chemotherapy delivery methods such as intraperitoneal chemotherapy have been evaluated in phase III trials with promising results, and are an area of future study.
An ongoing phase III international trial (TOPGEAR) will evaluate the use of ECF preoperatively compared with 2 cycles of ECF followed by chemoradiotherapy with 5-FU and radiotherapy to 45 Gy.
These conflicting results, as well as distinct differences in results between Eastern and Western nations, suggest that this issue may take many years to resolve. Interestingly, only one event occurred among patients harboring the PDGFR D842V mutation, believed to be imatinib-resistant. A high fraction of those on the 3-year arm dropped out (26%), other than for reasons of recurrence, raising the question of how to improve compliance when administering postoperative targeted therapies.
In East Asian countries, especially in Japan and Korea, D2 lymph node dissection has been regularly performed as a standard procedure. In addition, peritoneal washings can be obtained, although use of the findings to guide further treatment remains uncertain. For lesions of the gastroesophageal junction or the proximal third of the stomach, proximal subtotal gastrectomy can be performed.
To support current TNM staging criteria, 16 or more lymph nodes should be obtained at minimum and examined for an accurate N classification.
Interestingly, the beneficial D2 dissection impact on local recurrence and survival does not seem to be enhanced by postoperative chemoradiotherapy, whereas chemoradiotherapy appears to improve both categories after mere D1 dissections.
The Cancer and Leukemia Group B (CALGB) study 80101 compared intensified chemotherapy with ECF plus radiation compared with 5-FU and radiation and found no differences between these two regimens. Subgroup analysis revealed that the outcome did not differ based upon the type of lymphadenectomy (P = .80).
In the interim, it is appropriate to recommend adjuvant chemoradiotherapy to patients in North America who undergo initial gastrectomy.
Thus, tumor pathology and mutational status were both prognostic and predictive of recurrence-free survival after surgical resection of GIST (Lancet 373: 1097–1104, 2009). In Western countries, surgeons perform gastrectomy with D1 dissection only because D2 is associated with high mortality and morbidity compared to those associated with D1 alone but does not improve the 5-year survival rate. Ferlay, “Estimates of the worldwide mortality from 25 cancers in 1990,” International Journal of Cancer, vol. If total gastrectomy is necessary, transection of the distal esophagus and proximal duodenum is required, and omentectomy is performed. Removal of lymph nodes immediately adjacent to the stomach (paracardial, paragastric at the lesser or greater curvature, parapyloric) has been termed D1 dissection. Gastrectomy with extended lymphadenectomy should primarily be performed in specialized centers by experienced surgeons, and splenectomy and pancreatectomy should be avoided; for adequate staging, at least 16 lymph nodes should be removed and analyzed.
A complete pathologic response was achieved in 29% of patients who underwent resection after chemoradiation therapy.
Given these results, the use of postoperative chemoradiation therapy, usually with continuous infusion of 5-FU or capecitabine is the standard of care in the United States.


Still, since only a small percentage of patients underwent the recommended D2 dissection, further research is necessary before firm conclusions can be made in this area. Studies by CALGB and other groups do not support that intensification of therapy above that delivered on INT0116 will improve disease-free or overall survival. However, more recent studies have demonstrated that western surgeons can be trained to perform D2 lymphadenectomies on western patients with a lower morbidity and mortality. In Japan, there is a growing experience with more limited resections of early-stage gastric cancer. A more extensive D2 dissection would also remove retroperitoneal “second echelon” lymph nodes along the celiac trunk, left gastric artery, hepatic artery, splenic artery, and splenic hilus.
Population studies have suggested that adjuvant therapy is underutilized in the United States.
When extensive D2 lymph node dissection is preformed safely, there may be some benefit to D2 dissection even in western countries. This trend includes endoscopic mucosal resection of nonulcerated T1 N0 lesions and pylorus-preserving gastrectomy. In this paper, we present an update on the current literature regarding the extent of lymphadenectomy for advanced gastric cancer.1.
Laparoscopic resections are also being performed more frequently, with data from two randomized trials (KLASS and JCOG0912) showing no significant differences regarding morbidity and mortality between open and laparoscopic procedures to date for early-stage gastric cancer.
Although the prognosis of patients with advanced gastric cancer has improved with the introduction of effective chemotherapy [2] or adjuvant radiotherapy [3], surgical resection remains the primary therapeutic modality for curable advanced cancer. With regard to surgical procedure, dissection of regional LN is regarded an important part of en bloc resection for gastric cancer. However, there are significant differences in the extent of lymphadenectomy preformed by surgeons in different countries. Benedetti et al., “Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction,” The New England Journal of Medicine, vol.
Hermans et al., “Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients,” The Lancet, vol.
Calvo, “Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian gastric cancer study group prospective multicenter surgical study,” Journal of Clinical Oncology, vol. View at Publisher · View at Google Scholar · View at PubMed Japanese Gastric Cancer Association, “Japanese classification of gastric carcinoma—2nd English edition,” Gastric Cancer, vol. View at Google Scholar Japanese Gastric Cancer Association, Japanese Classification of Gastric Cancer, Kanehara & Co. Kinoshita et al., “Should systematic lymph node dissection be recommended for gastric cancer?” European Journal of Cancer, vol. View at Publisher · View at Google Scholar · View at Scopus Japanese Gastric Cancer Association, Gastric Cancer Treatment Guidelines, Kanehara & Co.
Final results of the randomized Dutch Gastric Cancer Group Trial,” Journal of Clinical Oncology, vol.
Boon et al., “Evaluation of the extent of lymphadenectomy in a randomized trial of Western- versus Japanese-type surgery in gastric cancer,” Journal of Clinical Oncology, vol. Whang-Peng, “Randomized clinical trial of morbidity after D1 and D3 surgery for gastric cancer,” British Journal of Surgery, vol. Fujii et al., “Effectiveness of paraaortic lymph node dissection for advanced gastric cancer,” Hepato-Gastroenterology, vol.
Natsugoe et al., “Paraaortic lymphadenectomy in patients with advanced carcinoma of the upper-third of the stomach,” Hepato-Gastroenterology, vol. Yamaoka et al., “Indications for paraaortic lymph node dissection in gastric cancer patients with paraaortic lymph node involvement,” Hepato-Gastroenterology, vol. Kosaka, “Results and controversial issues regarding a para-aortic lymph node dissection for advanced gastric cancer,” Surgery Today, vol. Yamamoto et al., “D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer,” The The New England Journal of Medicine, vol. Zhou et al., “Meta-analysis of effectiveness and safety of D2 plus para-aortic lymphadenectomy for resectable gastric cancer,” Journal of the American College of Surgeons, vol. Szczepanik, “Standard D2 versus extended D2 (D2+) lymphadenectomy for gastric cancer: an interim safety analysis of a multicenter, randomized, clinical trial,” American Journal of Surgery, vol. Randomized clinical trial of D2 and extended paraaaortic lymph adenectomy in patients with gastric cancer,” International Journal of Clinical Oncology, vol. Cao, “Systematic review of D2 lymphadenectomy versus D2 with para-aortic nodal dissection for advanced gastric cancer,” World Journal of Gastroenterology, vol. Aoyagi et al., “Surgery and clinicopathological features of gastric adenocarcinoma involving the esophago-gastric junction,” Kurume Medical Journal, vol. Isozaki, “Splenectomy for treatment of gastric cancer: Japanese experience,” World Journal of Surgery, vol. Ichikawa et al., “No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer,” British Journal of Surgery, vol. Shimizu et al., “Lack of benefit of combined pancreaticosplenectomy in D2 resection for proximal-third gastric carcinoma,” World Journal of Surgery, vol.
Okajima, “Pancreas-preserving total gastrectomy for proximal gastric cancer,” World Journal of Surgery, vol. Fong, “Atlas of upper gastrointestinal and hepato-pancreatico-biliary surger,” in Total Gastrectomy with Radical Systemic Lymphadenectomy, M.
Aizawa, “Splenectomy in cancer gastrectomy: recommendation of spleen-preserving for early stages,” International Surgery, vol. Kaibara, “Lymph node metastasis at the splenic hilum in proximal gastric cancer,” American Surgeon, vol. Maluenda, “A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma,” Surgery, vol.
Chung, “Randomized clinical trial of splenectomy versus splenic preservation in patients with proximal gastric cancer,” British Journal of Surgery, vol.



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