stomach cancer

Japanese: 胃癌

Concept Gastric cancer is an epithelial malignant tumor that develops in the gastric mucosa; if the stomach is divided into thirds, the upper, middle, and lower, it occurs almost equally in the middle and lower parts, accounting for 80% of all cases. Cancer that develops in the stomach after surgery is called cancer of the remnant stomach, and recently there has been an increase in cancer of the remnant stomach after surgery for early gastric cancer.
According to the 2009 statistics compiled by the Foundation for Epidemiological Cancer Research, malignant neoplasms are the number one cause of death, but the age-adjusted mortality rate for stomach cancer is on the decline, with the proportion of stomach cancer among all cancers per 100,000 population at 15.9% for men and 12.5% for women, almost half the figures in 1985, when the figures stood at 27.3% for men and 24.3% for women. However, the total number of deaths from stomach cancer nationwide was 50,017, making it the second most common cancer death by site after lung cancer. Furthermore, the number of people affected by stomach cancer in 2005 was 117,137, accounting for 17.3% of the total number of people affected by cancer of all sites, 676,075, making it the most common cancer. The incidence rate by age group shows a gradual decline, but as the average age increases, it is increasing among the elderly, and the total number of patients is actually increasing. By age, there is a peak in the 60s, and by gender, there are more men than women in both the number of cases and the number of deaths, but in the younger age group of 20 to 39, the number of women who are ill and the number of deaths are higher than men. The male to female ratio for gastric cancer overall is 1.9:1.
Histogenesis Research into the histogenesis of gastric cancer in Japan has a long history. Initially, due to the overwhelming majority of cases being advanced cancer and the influence of the German school, the ulcer cancer theory, which stated that gastric cancer developed from ulcers, was prevalent. Later, with the development and advancement of upper gastrointestinal endoscopy and the expansion of mass screening systems in Japan, many early gastric cancers were discovered and it became clear that gastric cancer developing from ulcers was extremely rare. Then, based on pathological examinations of many gastric cancer cases, the idea that gastric cancer develops against a background of gastritis such as chronic atrophic gastritis or intestinal metaplastic gastritis became established.
However, the cause of gastritis, which can be said to be the mother ground for the development of gastric cancer, especially chronic atrophic gastritis, was unknown, and it was thought to be a combination of various factors such as aging, salt intake, and ingestion of carcinogens. However, in 1993, Australian pathologist Warren and internist Marshall discovered and identified Helicobacter pylori in the stomach, and it was discovered that this bacterium causes chronic inflammation and intestinal epithelial metaplasia in the stomach, and a WHO working group concluded that Helicobacter pylori infection is the primary factor in gastric carcinogenesis. Many animal experiments were carried out to support this, and in particular, carcinogenesis experiments using gerbils, which are easily infected with Helicobacter pylori, revealed for the first time by Japanese researchers that although Helicobacter pylori alone does not cause gastric cancer, it does have a strong effect of enhancing the effects of other carcinogens and promoting carcinogenesis.
Therefore, infection with H. pylori during infancy or adolescence causes chronic inflammation in the gastric mucosa, which progresses over the long term to chronic atrophic gastritis and intestinal metaplastic gastritis, and gastric cancer develops during this process. However, the turning point at which chronic gastritis develops into gastric cancer, the branching point in the histogenesis of differentiated and undifferentiated gastric cancer, and the underlying genetic and epigenetic changes are still unclear, and the prevention of gastric cancer by eradicating H. pylori remains a challenge for the future.
This article focuses on the classification guidelines for gastric cancer set by the Japan Gastric Cancer Association. In 2010, the gastric cancer classification guidelines and gastric cancer treatment guidelines were significantly revised.
1) Macroscopic classification:
Gastric cancer is classified into six basic types, from type 0 to type 5, based on the mucosal surface. Type 0, which is the superficial type, was modified to make it easier to understand, based on the macroscopic classification of early gastric cancer in the Japan Endoscopy Society Classification (1962) (Figure 8-4-19). Within type 0, type IIc is the most common, accounting for around 70%, and of these, 70% are accompanied by ulcers (scars). Type IIa is the next most common, and type IIb, which is thought to be the earliest sign of cancer, is difficult to diagnose. Types 1 to 4 are advanced gastric cancers (Figure 8-4-20). Of these, type 3 is the most common, followed by types 2, 4, and 1, but the majority of type 4 cases are scirrhous gastric cancers, and the prognosis is extremely poor (Figures 8-4-21 to 8-4-30). Type 5 is unclassifiable and is basically advanced gastric cancer.
2) Stage classification:
The classification is based on a combination of three factors: depth of cancer invasion, lymph node metastasis, and metastasis to other sites, but unlike previous classifications, it has been revised to a new classification that incorporates the TNM classification (Table 8-4-5).
a) Depth of invasion: The stomach wall is divided into the mucosal layer (M), submucosa (SM), muscular layer (MP), subserosa (SS), and serosa (S), and if the invasion depth has reached S, it is divided into T1a to T4b, with the inclusion of direct invasion to other organs (SE) or not (SI). Regardless of the presence or absence of lymph node metastasis or metastasis to other organs, cancer that has remained at the submucosa is defined as early gastric cancer, and cancer that has invaded deeper than the muscular layer is defined as advanced cancer. Recently, more than 60% of diagnosed gastric cancers are early gastric cancer, and the ratio of M cancer to SM cancer is nearly 1:1.
b) Lymph node metastasis: The biggest change in the Gastric Cancer Guidelines is the rules for lymph node metastasis. The rules for lymph node metastasis in the stomach area remain the same, but the degree of metastasis has been classified into N0 to N3b according to the number of metastases in accordance with the TNM classification (Table 8-4-6). However, the rules for lymph node metastasis in the TNM classification are slightly different from those in the current Gastric Cancer Guidelines.
c) Metastasis to other sites: Metastasis other than regional lymph node metastasis is classified as M1, and liver metastasis (H), peritoneal metastasis (P), and peritoneal washing cytology (CY) are classified into three categories and described. In addition, if it is M1, even if it is early stage gastric cancer, it will be classified as stage IV.
3) Histological classification:
Gastric cancer is the only cancer with such a wide variety of histological types, each of which is found at a certain frequency. In the gastric cancer treatment guidelines, adenocarcinoma is considered the common type, and other histological types are considered special types. The common types are broadly divided into five types, and more specifically, into seven types (Table 8-4-7). To broadly classify these diverse cancers, Lauren's classification of diffuse and intestinal types, and Nakamura's classification of undifferentiated and differentiated cancers, mentioned above, are often used. Recently, a method of dividing cancers into three types based on immunohistochemical staining of mucus: gastric type, intestinal type, and mixed gastrointestinal type, has also been proposed. In general, as cancer develops and progresses, the histological type changes from differentiated to poorly differentiated to undifferentiated.
Growth and progression It is not entirely clear what type of early gastric cancer will develop and progress into what type of advanced gastric cancer. In general, type 0-IIb early gastric cancer is thought to be the initial stage, but it is only clinically possible to diagnose it once its shape has changed to a certain extent, such as types 0-IIa and 0-IIc. In terms of examining histogenesis, it is important to diagnose smaller cancers, and cancers measuring 5 mm or less are called microgastric cancers, and those measuring 1 cm or less are called small gastric cancers. More than 80% of such small cancers are histologically differentiated, but approximately half of general gastric cancers are undifferentiated or poorly differentiated adenocarcinomas, and it is therefore thought that there may be differences in the growth and progression of differentiated and undifferentiated cancers.
In either case, as the cancer develops, one of the lesions progresses to a protruding type such as type 0-IIa, which then develops further into type I or type 0-IIa + IIc, and then to type 1 or 2 advanced gastric cancer, and some to type 3. Some type I cancers originate from polyps, especially adenomas. On the other hand, depressed types such as type 0-IIc continue to infiltrate deeply and progress to type 3 or 4 advanced gastric cancer. Many type 0-IIc lesions are accompanied by ulcers, but some of them undergo a repeated healing and recurrence of the ulcer, known as a malignant cycle, and progress to cancer relatively slowly. Therefore, although type 0-III was created based on the assumption that ulcers would develop into cancer, it actually represents one stage of this malignant cycle.
There are three types of metastasis and recurrence of gastric cancer: 1) lymph node metastasis, 2) hematogenous metastasis to the lungs, liver, or bone marrow, and 3) direct metastasis to the peritoneum (peritoneal seeding). In early gastric cancer, most recurrences after curative surgery are hematogenous metastasis to the liver or lungs, and the histological type is differentiated. In advanced gastric cancer, all types of metastasis and recurrence can occur, but undifferentiated and poorly differentiated adenocarcinomas are particularly prone to peritoneal seeding, and a typical example is scirrhous gastric cancer. Scirrhous gastric cancer is a type of cancer in which cancer cells do not form glandular ducts but diffusely infiltrate with the proliferation of a large amount of fibrous connective tissue, and clinically causes poor extension of the stomach wall and presents an X-ray image known as a leather bottle appearance (Figure 8-4-31). This applies to most type 4 gastric cancers and some type 3 gastric cancers. In addition, when undifferentiated cancer metastasizes to the bone marrow, it can show signs of DIC (disseminated intravascular coagulation), a condition known as bone marrow carcinomatosis, which can cause bleeding tendency and a poor prognosis.
Clinical symptomsThere are no symptoms specific to gastric cancer, but as the cancer progresses, symptoms such as bleeding, stenosis, loss of appetite, weight loss, and sometimes abdominal distension due to ascites may appear. Therefore, in the early stages of gastric cancer, it is difficult to suspect gastric cancer based on clinical symptoms, and it is particularly characteristic that symptoms are less likely to appear even as the disease progresses in the middle and upper body of the stomach. Therefore, it is important to instruct middle-aged and elderly people at risk of gastric cancer to undergo medical examinations and regular checkups.
Diagnosis: Existence diagnosis, qualitative diagnosis, metastasis diagnosis, etc. are performed to determine the treatment plan.
1) Existence diagnosis:
Diagnosis is by X-ray contrast examination or endoscopic examination, but endoscopic examination is superior in diagnosing early gastric cancer. However, many endoscopic examinations have limitations, and narrowing down high-risk individuals is an issue. Recently, risk assessment of gastric cancer has been performed by ABC screening, which combines the presence or absence of H. pylori (Hp) infection with blood pepsinogen (PG) measurement, which indicates the degree of atrophy of the gastric mucosa. In other words, if Hp(-) and PG(-) are group A, which have almost no risk of gastric cancer, Hp(+) and PG(-) are group B, Hp(+) and PG(+) are group C, and Hp(-) and PG(+) are group D, the hazard ratio for the development of gastric cancer is 9.8 for group B, 19.6 for group C, and 120.4 for group D, when group A is set to 1, and this is an indicator for regular endoscopic examination according to each group.
In endoscopic examinations, in addition to regular observations of the stomach, it is recommended to perform endoscopic examinations using image enhancement in order to avoid overlooking small cancers. Specifically, contrast enhancement can be achieved by spraying the blue color indigo carmine into the stomach, or narrow band imaging (NBI) [⇨8-1-3)-(2)] or flexible spectral imaging (FICE) using digital functions, and detailed diagnosis can be made by adding magnified observations.
2) Qualitative diagnosis:
The final diagnosis of gastric cancer is made by histopathological diagnosis of biopsy. It can be difficult to distinguish from carcinoid and malignant lymphoma, so diagnosis is made by immunohistochemical staining or special staining. Diagnosis of the histologic type of gastric cancer is also important, and treatment is selected based on that. Recently, attempts have been made to diagnose the histologic type without taking a biopsy using the above-mentioned image-enhanced observation, i.e., "virtual biopsy" and "virtual pathology." In addition, when performing surgery or endoscopic treatment, it is important to diagnose not only the presence of cancer but also the extent of cancer, so biopsies are taken from appropriate areas. Diagnosis of the depth of invasion is also important for treatment, and is judged by endoscopic images and diagnosed by endoscopic ultrasound (EUS). On EUS, the normal stomach wall is depicted in five layers, and the depth of invasion is diagnosed based on the changes in each layer. [⇨Figure 8-1-11] In addition, in cases of advanced gastric cancer where peritoneal dissemination is suspected, peritoneal washing cytology may be performed under laparoscopy to determine the treatment plan.
3) Metastasis diagnosis:
CT and abdominal ultrasound are the basic examinations. If infiltration into surrounding organs is suspected, an MRI scan is performed. PET scans have a low detection rate for gastric cancer and are not particularly useful at present. There are no tumor markers specific to gastric cancer, but CEA and CA19-9 are the basics, and AFP and CA72-4 are added to these to aid in the diagnosis of AFP-producing gastric cancer and undifferentiated gastric cancer.
Differential diagnosis
1) Gastric polyps and adenomas:
The problem lies in differentiating type I from hyperplastic polyps, and types 0-IIa from adenomas. Hyperplastic polyps have clearly visible capillaries developed around the apex, which differs from the unclear faint redness of cancer. Adenomas are pale-white in appearance overall, relatively smooth and uniformly elevated, whereas cancer is heterogeneous, has a somewhat rough surface and is faintly reddish. As it is not uncommon for parts of polyps or adenomas to become cancerous, a final diagnosis is made by biopsy, polypectomy, or endoscopic resection.
2) Gastric erosion:
It is important to differentiate this from minute type 0-IIc early gastric cancer. It is characterized by a reddish color on the eroded surface and a stellate change on the concave surface, but diagnosis is difficult. Benign gastric erosions represent gastritic changes and often occur multiple times, so if a solitary gastric erosion is seen, cancer should be suspected and a biopsy should be performed.
3) Gastric ulcer:
It can be difficult to differentiate between acute gastric ulcers and type 0-III early gastric cancer, and between multiple gastric ulcer scars and type 0-IIc + III early gastric cancer. Particularly in the acute phase, diagnosis should be made again by endoscopic examination after treatment for the ulcer. In the latter case, diagnosis is made by observing the characteristics of the concentrated folds and the shape of the concave surface. The key to differentiation is whether the border of the concave can be traced as a continuous line when dye is sprayed, but ultimately a biopsy is required for diagnosis.
4) Malignant lymphoma:
The problem is how to differentiate MALT lymphoma from superficial spreading type 0-IIc, 0-IIc+III early gastric cancer, type 4 gastric cancer, and scirrhous gastric cancer. MALT lymphoma is characterized by an unclear border of the lesion, frequent attachment of whitish mucus to the surface, a soft impression of a slightly elevated surface, and good extension of the stomach wall compared to the thickness of the folds. It can also be difficult to differentiate between elevated malignant lymphoma and type 2 advanced gastric cancer, but in the former, the ulcer margin is relatively smooth and the ridge appears to be uniformly raised from under the mucosa, presenting a so-called earlobe-like appearance.
5) Submucosal tumor:
When distinguishing between type 0-I early gastric cancer and type 1 advanced gastric cancer, submucosal tumors are characterized by the surface being similar to the surrounding mucosa and the elevated folds exhibiting bridging folds.
Endoscopic ultrasound is also useful for differential diagnosis.
Treatment Selection of treatment for gastric cancer is based on the "Gastric Cancer Treatment Guidelines" set out by the Japan Gastric Cancer Association (Figure 8-4-32). Treatment options include endoscopic therapy, surgery, and chemotherapy using anticancer drugs. There is currently little evidence regarding the effectiveness of radiation therapy for gastric cancer.
When resection is performed including the primary tumor, the degree of cure is expressed in terms of the amount of tumor remaining (R) instead of the previous level of cure, with R0 being a curative resection and R1 and R2 being non-curative. The evaluation of curability in endoscopic treatment is different from this, with a resection being evaluated as curative if all the eligibility criteria are met, and a non-curative resection otherwise.
1) Treatment for early gastric cancer:
The basic approach is to remove the lesion, and methods available for this include endoscopic resection and standard gastrectomy. In principle, endoscopic resection is indicated for intramucosal cancer (M cancer) without lymph node metastasis, and for differentiated lesions measuring 2 cm or less in size with no ulcers within the lesion. Methods for this include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). ESD allows for gastric mucosal resection regardless of size, and is applicable to differentiated M cancer measuring 2 cm or more in size without ulcers, or ulcers but 3 cm or less, and also undifferentiated cancer measuring 2 cm or less in size without ulcers, as there is almost no lymph node metastasis. Therefore, its indications have been expanded.
In the case of gastrectomy, limited surgery is performed to reduce lymph node dissection and the extent of gastrectomy, reduce surgical invasiveness, and improve postoperative quality of life by preserving function. Recently, limited surgery has been actively performed under laparoscopy (assistance), with good results. Furthermore, sentinel node navigation surgery (SNNS) has been attempted with the aim of reducing the extent of lymph node dissection. In this method, a radiolabeled radioisotope is injected into the submucosa around the lesion before surgery, or a dye is injected during surgery, and the lymph flow and lymph nodes are identified using this as a guide to perform the minimum necessary lymph node resection, and its validity is being examined.
2) Treatment for advanced gastric cancer:
Surgery is the standard procedure, which involves lymph node dissection up to two groups, and distal gastrectomy, which involves removal of more than two-thirds of the stomach. Results of an RCT have shown that extensive surgery including para-aortic lymph node dissection has no preventive effect (Sasako et al., 2008). In cases of advanced gastric cancer where a cure is not expected, palliative surgery is performed to alleviate urgent symptoms such as bleeding and stenosis, and debulking surgery is performed to reduce the tumor burden and extend life through multidisciplinary treatment.
3) Chemotherapy for gastric cancer:
Chemotherapy is broadly divided into three types: neoadjuvant chemotherapy, which aims to reduce lymph node metastasis in preparation for curative surgery; adjuvant chemotherapy, which aims to prevent recurrence after surgery; and chemotherapy for inoperable or recurrent gastric cancer. Anticancer drugs include 5-FU, cisplatin (CDDP), irinotecan (CPT-11), and taxanes, administered alone or in combination. A large-scale randomized controlled trial was conducted to evaluate the effectiveness of adjuvant chemotherapy after curative surgery for stage II and III cancer, and the administration of S-1 was found to significantly increase life expectancy, making it the standard treatment (Sakuramoto et al., 2007). On the other hand, clinical trials have shown that S-1 + CDDP is the first choice for inoperable or recurrent gastric cancer. In addition, it has recently been shown that the administration of trastuzumab, an antagonist of Her2, can increase life expectancy in recurrent cases of gastric cancer (approximately 20% of gastric cancers), which is a receptor for growth factors, as in the case of breast cancer, and this treatment is now covered by insurance. As such, it is clear that chemotherapy has a life-prolonging effect; however, the cancer response rate does not necessarily coincide with the life-prolonging effect, and RCTs and other methods are currently being used to determine which drugs and combinations are effective.
Treatment Results According to a report compiled by the National Registration Committee of the Japan Gastric Cancer Association on cases in 2001, the resection rate was 97%, with an operative mortality rate (death within 30 days after surgery) of 0.6%. The cumulative 5-year survival rates by stage after gastrectomy were I: 90.3%, II: 73.1%, III: 44.5%, IV: 15.8%, and overall 69.1%.
Prevention It has been shown epidemiologically and experimentally that Helicobacter pylori infection plays a major role in the development of gastric cancer. Therefore, attempts have been made to prevent the development of gastric cancer by eradicating Helicobacter pylori. As a result, experimentally, eradication of Helicobacter pylori early after infection, i.e. at a young age, suppressed the development of gastric cancer, but eradication after a certain period of infection was not effective. Clinically, a clinical trial in China reported that eradication had no effect on suppressing gastric cancer in cases where intestinal metaplasia or dysplasia of the gastric mucosa had occurred (Wong). Furthermore, eradication after endoscopic resection delays the time until the development of gastric cancer, but is said to have little effect in suppressing the development itself. Therefore, eradication of Helicobacter pylori in young people may be effective, but in middle-aged and elderly people, early detection is the primary factor for preventing gastric cancer, and identifying high-risk groups is a challenge. [Kamishige Norio]
■ References <br /> Cancer Research Promotion Foundation: Cancer Statistics 2009 Edition, 2011. Japanese Gastric Cancer Association: Guidelines for the Treatment of Gastric Cancer (14th Edition): Kanehara Publishing, Tokyo, 2010. Japanese Gastric Cancer Association: Gastric Cancer Treatment Guidelines for Physicians, October 2010 Revised (3rd Edition), Kanehara Publishing, Tokyo, 2010.
Sakuramoto S, Sasako M, et al: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med, 357: 1810-1820, 2007.
Sasako M, Sano T, et al: D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med, 359: 453-462, 2008.

Table 8-4-5
Stage classification of gastric cancer ">

Table 8-4-5

Table 8-4-6
How to describe lymph node metastasis

Table 8-4-6

Table 8-4-7
Histological classification of gastric cancer ">

Table 8-4-7

Fig. 8-4-19
Subclassification of superficial (type 0) gastric cancer ">

Fig. 8-4-19

Fig. 8-4-20
Macroscopic classification of advanced gastric cancer ">

Fig. 8-4-20

Fig.8-4-32
Recommended treatment options for gastric cancer in daily practice ">

Fig.8-4-32

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

概念
　胃癌は胃粘膜から発生する上皮性の悪性腫瘍で，胃を上部，中部，下部に三等分すると，中部と下部に発生する場合がほぼ同等で全体の80％を占める．また，術後の胃に発生する癌を残胃の癌とよぶが，最近では早期胃癌術後の残胃の癌が増加しつつある．
疫学
　がん研究振興財団の2009年度集計によると悪性新生物が死亡率の第1位であるが，そのなかで胃癌の年齢調整死亡率は低下傾向にあり，人口10万人当たりの全癌に占める胃癌の割合は男性では15.9％，女性では12.5％であり，1985年の男性27.3％，女性24.3％と比べるとほぼ半減している．しかし，全国の胃癌死亡総数は50017人であり，部位別の癌死亡数では肺癌についで第2位である．さらに，胃癌の罹患数は2005年では117137人と，全部位での癌罹患数 676075人の17.3％と最も多い．年齢階級別の罹患率でみると徐々に低下傾向が認められるが，平均年齢の延長に伴い高齢者においては上昇しており，患者総数としてはむしろ増加している．　年齢別では，60歳代にピークがあり，性別では，罹患数，死亡数ともに男性が女性に比して多いが，20～39歳の若年ではむしろ女性の方が罹患数，死亡数ともに男性を上回っている．胃癌全体の男女比は1.9：1である．
組織発生
　わが国における胃癌の組織発生についての研究の歴史は長く，当初は進行癌が圧倒的に多かったことやドイツ学派の影響もあり，胃癌は潰瘍から発生するとする潰瘍癌説が有力であった．その後，わが国での上部消化管内視鏡の開発，発展，集団検診制度の充実などにより早期胃癌が多く発見され，潰瘍からの胃癌発生はきわめてまれであることが判明した．そして，多くの胃癌症例の病理学的検討を基に，胃癌は慢性萎縮性胃炎，あるいは腸上皮化生性胃炎などの胃炎を背景として発生するという考えが定着した．
　しかしながら胃癌発生の母地といえる胃炎，特に慢性萎縮性胃炎の原因については不明で，老化現象，塩分摂取，発癌物質摂取などさまざまな原因が複合的に作用すると考えられていた．ところが1993年にオーストラリアの病理学者であるWarrenと内科医であるMarshallによりピロリ菌（Helicobacter pylori）が胃の中から発見，同定され，この菌が胃に慢性炎症と腸上皮化生を発生させることが判明し，WHOのワーキンググループからピロリ菌感染は胃発癌の第一義的因子であると結論された．このことを裏付けるために動物による実験が数多く行われ，とくにピロリ菌の感染が容易なスナネズミを用いた発癌実験により，ピロリ菌単独では胃癌は発生しないが，ほかの発癌物質の作用を増強し，発癌を促進する作用を強力に有していることがわが国の研究者によってはじめて明らかにされた．
　したがって，乳幼児期や若年期にピロリ菌に感染することにより胃粘膜に慢性炎症が生じ，長期経過後に慢性萎縮性胃炎，腸上皮化生性胃炎へと進展し，その過程の中から胃癌が発生することになる．しかしながら，慢性胃炎から胃癌になるターニング・ポイント，分化型胃癌，未分化型胃癌の組織発生の分岐点の解明，それらの背景にあるジェネティック（遺伝的），エピジェネティックな変化についてはまだまだ不明であり，さらにピロリ菌の除菌による胃癌の予防については今後の課題となっている．
分類
　日本胃癌学会による胃癌取扱い規約を中心に述べる．なお，2010年に胃癌取扱い規約ならびに胃癌治療ガイドラインは大幅に改訂された．
1）肉眼分類：
胃癌を粘膜面からみて0型から5型までの6つに基本分類する．表在型である0型については，日本内視鏡学会分類（1962年）の早期胃癌の肉眼分類を参考とし，より分かりやすいように改変された（図8-4-19）．0型の中ではⅡc型が最も多く70％前後を占め，さらにこれらのうちの70％が潰瘍（瘢痕）を伴っている．次に多いのがⅡa型であり，癌の最も初期像と思われるⅡb型は診断が難しい．1型から4型までは進行胃癌である（図8-4-20）．これらのなかでは3型が最も多く，2型，4型，1型と続くが，4型はスキルス胃癌がその大半であり，予後はきわめて悪い（図8-4-21～8-4-30）．5型は分類不能のものであり基本的には進行胃癌である．
2）進行度分類：
癌の浸潤の深さ，リンパ節転移，それ以外の部位への転移の3つの因子を組み合わせて分類しているが，これまでと異なりTNM分類を組み入れた新しい分類に改変された（表8-4-5）．
　a）深達度：胃壁を粘膜層（M），粘膜下層（SM），筋層（MP）漿膜下層（SS），漿膜（S）に分け，深達度がSに達している場合は，直接他臓器への浸潤のなし（SE），あり（SI）を加えてT1a～T4bに分けている．そしてリンパ節転移や他臓器への転移の有無にかかわらず，粘膜下層までにとどまっている癌を早期胃癌，筋層以深に及んでいる癌を進行癌と定義している．最近では，診断される胃癌の60％以上が早期胃癌であり，M癌とSM癌との比率はほぼ1：1である．
　b）リンパ節転移：胃癌取扱い規約で一番変わったのがリンパ節転移の規定である．胃の領域リンパ節の規定はそのままであるが，転移の程度についてはTNM分類に準拠し転移個数によってN0～N3bに分類した（表8-4-6）．なお，TNM分類におけるリンパ節転移の規定は，今回の胃癌取扱い規約の規定とはやや異なっている．
　c）ほかの部位への転移：領域リンパ節転移以外の転移をM1とし，特に肝転移（H），腹膜転移（P），腹腔洗浄細胞診（CY）はそれぞれ3つに分類し，記載することになった．なお，M1であれば，たとえ早期胃癌であってもステージ Ⅳとなる．
3）組織型分類：
胃癌のように多様な組織型があり，それぞれが一定程度の頻度で認められる癌はほかにはない．胃癌取扱い規約では，腺癌を一般型，それ以外の組織型を特殊型としている．一般型は，大きくは5つ，細かく分けると7つに分けられている（表8-4-7）．このような多様な癌を大別する目的で，Laurenによるびまん型と腸型の分類，前述の中村による未分化型癌と分化型癌の分類がよく用いられている．最近では，粘液の免疫組織化学染色により胃型，腸型，胃腸混合型の3つに分ける方法も提唱されている．一般的には，癌が発育・進展するにつれて分化型から低分化，未分化型に組織型が変化していく．
発育と進展
　どのような早期胃癌がどのような進行胃癌に発育・進展していくかについては必ずしも明確ではない．一般的には0-Ⅱb型早期胃癌が初発と考えられているが，臨床的に診断可能なのは0-Ⅱa型や0-Ⅱc型のようにある程度形状が変化してからである．組織発生を検討する意味でより小さな癌を診断することは重要であり，大きさ5 mm以下の癌を微小胃癌，1 cm以下のものを小胃癌と呼称している．このような小さな癌の組織型は80％以上が分化型癌であるが，一般の胃癌では約半数が未分化型癌，低分化腺癌であることから，分化型癌と未分化型癌の発育と進展に差がある可能性が考えられている．
　いずれにしても，癌が発育するにつれて片方は0-Ⅱa型のような隆起型へ進展し，さらに発育してⅠ型，あるいは0-Ⅱa＋Ⅱc型，そして1型，2型の進行胃癌へ，一部は3型へと進展していくものと考えられている．また，Ⅰ型の一部にはポリープ，特に腺腫から発生した癌が含まれている．一方，0-Ⅱc型のような陥凹型はそのまま深く浸潤していき，3型あるいは4型の進行胃癌へ進展していく．また，多くの0-Ⅱc型は病変内に潰瘍を伴うが，その一部は悪性サイクルとよばれる潰瘍の治癒，再燃を繰り返し，癌としての進展が比較的遅いものがある．したがって，0-Ⅲ型は潰瘍からの癌化を想定して考えられた分類であるが，実際はこの悪性サイクルの一段階を表していることになる．
転移・再発
　胃癌の転移・再発形式には，①リンパ節転移，②肺や肝臓，骨髄への血行性転移，③腹膜への直接転移（腹膜播種）の3つがある．早期胃癌では，根治手術後の再発のほとんどは肝臓，肺への血行性転移であり，組織型では分化型である．進行胃癌では，すべての転移・再発形式をとるが，特に未分化型，低分化腺癌では腹膜播種を起こしやすいことが特徴的であり，その代表がスキルス胃癌である．スキルス胃癌（scirrhous gastric cancer）とは，癌細胞が腺管を形成せずに多量の線維性結合組織の増生を伴ってびまん性に浸潤するもので，臨床的には胃壁の伸展不良をもたらしleather bottle様とよばれるX線像を呈する（図8-4-31）．4型胃癌の大部分と3型胃癌の一部が該当する．また，未分化型癌が骨髄に転移するとDIC（播種性血管内凝固症）の所見を呈することがあり，骨髄癌症とよばれ出血傾向を呈し予後不良である．
臨床症状
　胃癌に特有の症状はなく，癌の進展に伴い出血，狭窄症状，食欲低下，体重減少，ときには腹水による腹部膨満を呈する．したがって，早期胃癌の段階では臨床症状から胃癌を疑うことは困難であり，特に胃体中部，上部の場合は進行しても症状が出にくいことが特徴的であり，胃癌のリスクのある中年・高齢者には検診や定期的な検査を受けるよう指導することが重要である．
診断
　存在診断，質的診断，転移診断などを行って治療方針を決定する．
1）存在診断：
Ｘ線造影検査あるいは内視鏡検査で診断するが，早期胃癌の診断においては内視鏡検査の方がすぐれている．ただし，多数の内視鏡検査には限界があり，胃癌のハイリスクの絞り込みが課題となっている．最近では，H．pylori（H.p.）感染の有無と胃粘膜の萎縮の程度を表す血中ペプシノーゲン（PG）測定を組み合わせたABC検診による胃癌のリスク評価が行われつつある．すなわち，胃癌のリスクがほとんどないH.p.（−），PG（−）をＡ群とし，H.p.（＋），PG（−）をＢ群，H.p.（＋），PG（＋）をＣ群，H.p.（−），PG（＋）をＤ群とすると，胃癌発生のハザード比はA群を1とした場合，B群で9.8，Ｃ群で19.6，D群で120.4となり，それぞれの群に応じた定期的な内視鏡検査の指標とするものである．
　内視鏡検査においては，小さな癌を見逃さないために通常の胃内の観察に加えて画像強調による内視鏡検査を行うことが奨められる．具体的には，青色のインジゴカルミンの胃内散布によるコントラストの強調，あるいは狭帯域光観察（narrow band imaging：NBI）【⇨8-1-3）-（2）】やデジタル機能を利用したFICE（Flexible Spectral Imaging）など，さらには拡大観察を加えて詳細な診断が可能となっている．
2）質的診断：
胃癌の最終診断は生検の病理組織学的診断による．カルチノイドや悪性リンパ腫との鑑別が困難な場合もあり，免疫組織化学的染色や特殊染色を行って診断する．また，胃癌の組織型診断も重要で，それに基づいた治療法の選択が行われる．最近では，生検を取ることなく上記の画像強調観察による組織型診断，すなわち“virtual biopsy（仮想生検）”，“virtual pathology（仮想病理組織診）”の試みがなされている．また，手術や内視鏡的治療を行う場合は癌の存在診断のみならず癌の範囲診断も重要であり，適切な部位から生検を採取する．深達度診断も治療に当たって重要で内視鏡像にて判断するとともに，超音波内視鏡（endoscopic ultrasonography：EUS）にて診断する．EUS上では通常の胃壁は5層に描出され，それぞれの層の変化に基づいて深達度診断を行う．【⇨図8-1-11】．また，高度進行胃癌で腹膜播種が疑われる場合は腹腔鏡下に腹腔内洗浄細胞診を行い，治療方針を決定することがある．
3）転移診断：
CT，腹部超音波検査が基本である．周囲臓器への浸潤が疑われる場合はMRI検査を行う．PET検査は胃癌の場合は検出率が低く現状ではあまり有用ではない．腫瘍マーカーとして胃癌に特有のものはないがCEA，CA19-9が基本であり，これにAFPやCA72-4を加えてAFP産生性胃癌や未分化型胃癌の診断補助とする．
鑑別診断
1）胃ポリープ，胃腺腫：
Ⅰ型は過形成性ポリープと，0-Ⅱa型は腺腫との鑑別が問題となる．過形成性ポリープは頂部を中心に発達した毛細血管が明瞭に見え，癌の場合の不明瞭な淡い発赤とは異なる．腺腫の場合は全体に蒼白色調で比較的平滑で隆起も均一であるが，癌の場合は不均一で表面もやや粗造で淡く発赤調を呈する．ポリープや腺腫の一部が癌化していることも少なくないので，生検あるいはポリペクトミーや内視鏡的切除にて最終診断する．
2）胃びらん：
微小な0-Ⅱc型早期胃癌との鑑別が重要である．びらん面における発赤の色合いや陥凹面の星芒状変化が特徴とされるが，診断は困難である．良性の胃びらんは胃炎性変化を表すので多発することが多いため，単発性の胃びらんを見たら癌を疑って生検すべきである．
3）胃潰瘍：
急性期の胃潰瘍と0-Ⅲ型早期胃癌との鑑別，多発胃潰瘍瘢痕と0-Ⅱc＋Ⅲ型早期胃癌との鑑別が難しい場合がある．特に急性期では，潰瘍に対する治療を行った後に再度内視鏡検査にて診断すべきである．後者の場合は，集中するひだの性状や陥凹面の形状を観察して診断する．色素散布を行って陥凹する境界が連続性に追えるか否かが鑑別のポイントであるが，やはり最終的には生検による診断を行う．
4）悪性リンパ腫：
MALTリンパ腫と表層拡大型の0-Ⅱc型，0-Ⅱc＋Ⅲ早期胃癌，あるいは4型胃癌，スキルス胃癌との鑑別が問題となる．MALTリンパ腫では病変の境界が不鮮明であること，表面に白色調の粘液の付着が多いこと，軽度隆起した面がやわらかい印象でひだの太さに比して胃壁の伸展が良好であること，などが特徴である．また，隆起型の悪性リンパ腫と2型進行胃癌との鑑別に苦慮することがあるが，前者では潰瘍辺縁は比較的平滑で周堤も均一に粘膜下から盛り上がるような印象で，いわゆる耳たぶ様の所見を呈する．
5）粘膜下腫瘍：
0-Ⅰ型早期胃癌，1型進行胃癌との鑑別において，粘膜下腫瘍では表面が周囲粘膜と同様で，押し上げられたひだが架橋（bridging fold）を呈することが特徴的である．
超音波内視鏡検査も鑑別に有用である．
治療
　胃癌の治療の選択にあたっては，日本胃癌学会による「胃癌治療ガイドライン」に沿って行う（図8-4-32）治療法としては，内視鏡的治療，手術，そして抗癌薬による化学療法がある．胃癌に対する放射線治療の効果については現在までのところエビデンスは乏しい．
　原発巣を含めて切除が行われた場合，これまでの根治度にかわりその程度を腫瘍の遺残（R）で表すことになり，R0は治癒切除，R1，R2は非治癒切除となる．内視鏡的治療における根治性の評価はこれとは異なり，適応基準をすべて満たした場合を治癒切除，それ以外は非治癒切除と評価する．
1）早期胃癌に対する治療法：
病巣の切除が基本であるが，その方法として内視鏡的切除と通常の胃切除術とがある．内視鏡的切除の原則はリンパ節転移のない粘膜内癌（M癌）であり，大きさ2 cm以下，分化型で病巣内に潰瘍がないものが適応とされている．その方法としては，EMR（endoscopic mucosal resection）法とESD（endoscopic submucosal dissection）法とがある．ESD法では大きさに関係なく胃粘膜切除が可能であること，また，分化型M癌で大きさ2 cm以上で潰瘍を伴わない場合，あるいは潰瘍を伴うが3 cm以下の場合，さらには2 cm以下の潰瘍を伴わない未分化型であればリンパ節転移がほとんどないため，適応が拡大されている．
　胃切除術の場合は，リンパ節郭清と胃切除範囲を縮小し，手術侵襲の低減と機能温存による術後のQOLの向上を目的とした縮小手術が行われる．最近では，腹腔鏡（補助）下に縮小手術が積極的に行われており，良好な成績を得ている．さらに，リンパ節郭清範囲の縮小を目的にsentinel node navigation 手術（SNNS）が試みられている．病巣周囲の粘膜下層内に放射線でラベルしたRI物質を術前に，あるいは色素を術中に注入し，それをガイドにリンパ流とリンパ節を同定して必要最小限のリンパ節切除を行う方法であり，その妥当性が検討されている．
2）進行胃癌に対する治療法：
手術が基本で2群までのリンパ節郭清と，幽門側胃切除では胃の2/3以上の切除を行う定型手術が行われる．大動脈周囲リンパ節郭清を伴う拡大手術については，RCTの結果，その予防的効果がないことが示されている（Sasakoら， 2008）．また，高度進行胃癌で治癒が望めない症例に対しては，出血や狭窄などの切迫症状を改善するための緩和（姑息）手術と，腫瘍量を減らして集学的治療により延命を図る減量手術が行われる．
3）胃癌に対する化学療法：
化学療法としては大きく分けて，根治的手術を目的にリンパ節転移の縮小を目指した術前化学療法（neoadjuvant chemotherapy），術後の再発予防を目的とした術後補助化学療法（adjuvant chemotherapy），そして手術不能・再発胃癌に対する化学療法の3つがある．抗癌剤としては5-FU系薬剤，シスプラチン（CDDP），イリノテカン（CPT－11），タキサン系薬剤が単独あるいは組み合わせて投与されている．ステージ Ⅱ，Ⅲの根治手術後の補助化学療法の効果について大規模のRCTが行われ，S-1投与による有意な延命効果の上乗せが認められ標準治療となっている（Sakuramotoら， 2007）．一方，切除不能，あるいは再発胃癌に対しては，臨床試験の結果S-1＋CDDPが第一選択となっている．また，増殖因子の受容体であるHer2陽性胃癌（胃癌の約20%）の再発例に対して，乳癌の場合と同様にその拮抗薬であるトラスツズマブ投与により延命効果があることが最近になって示され，保険適応となった．このように化学療法による延命効果は明らかであるが，癌の奏効率と延命効果とは必ずしも一致しないことが問題であり，どの薬剤，どの組み合わせが効果的であるかについては現在RCTなどにて検討されている．
治療成績
　日本胃癌学会全国登録委員会による2001年度症例の集計報告によると，切除率97％，手術死亡率（術後30日以内死亡）0.6％で，胃切除後のステージ別の累積5年生存率は，Ⅰ：90.3％，Ⅱ：73.1％，Ⅲ：44.5％，Ⅳ：15.8％，全体で69.1％である．
予防
　胃癌の発生に大きな役割を果たしているのがピロリ菌の感染であることは，疫学的および実験的にも示されている．そこで，ピロリ菌の除菌による胃癌発生予防の試みが行われた．その結果，実験的にはピロリ菌感染後早期，すなわち若年での除菌は胃癌発生を抑制したが，感染後一定期間後の除菌は有効ではなかった．臨床的にも中国における治験で，腸上皮化生や胃粘膜の異形成が生じている場合は除菌による胃癌抑制効果がなかったと報告されている（Wong）．また，内視鏡的切除後に除菌した場合，その後の胃癌の発生までの時間は遅らせるが，発生そのものを抑制する効果は低いとされている．したがって，若年のピロリ菌感染者の除菌は有効である可能性があるが，中年，老年者では早期発見が胃癌予防の第一義的要因であり，ハイリスク群の拾い出しが課題となる．［上西紀夫］
■文献
がん研究振興財団：がんの統計2009年度版，2011．日本胃癌学会：胃癌取扱い規約（第14版）：金原出版，東京，2010．日本胃癌学会：胃癌治療ガイドライン医師用2010年10月改訂（第3版），金原出版，東京，2010．
Sakuramoto S, Sasako M, et al: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med, 357: 1810-1820, 2007.
Sasako M, Sano T, et al: D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med, 359: 453-462, 2008.

表8-4-5
胃癌の進行度分類">

表8-4-5

表8-4-6
リンパ節転移の記載法">

表8-4-6

表8-4-7
胃癌の組織型分類">

表8-4-7

図8-4-19
表在型（０型）胃癌の亜分類">

図8-4-19

図8-4-20
進行胃癌の肉眼分類">

図8-4-20

図8-4-32
日常診療で推奨される胃癌の治療法の選択">

図8-4-32