Seronegative alpha-fetoprotein-producing early gastric cancer treated with endoscopic mucosal resection and additional surgery

A 67-year-old man visited our hospital for the treatment of gastric carcinoma. Endoscopic mucosal resection was performed, however, histological examination of the resected specimen revealed tumor invasion to the submucosal layer with vessel invasion. Immunohistological studies were carried out on resected specimens and part of the cancerous lesion showed a positive reaction for alpha-fetoprotein (AFP), but the serum AFP level was normal. Additional distal gastrectomy with lymph node dissection revealed lymph node metastasis although there was no apparent finding of lymph node swelling by preoperative diagnostic imaging. This patient remains alive without disease for 3 years after surgery.     

EN BLOC REMOVAL OF A GASTRIC CARCINOID TUMOR USING ENDOSCOPIC SUBMUCOSAL DISSECTION TECHNIQUES

Endoscopic submucosal dissection (ESD) has recently been applied to the resection of gastric submucosal tumors other than carcinoid tumors. We describe a case of gastric carcinoid tumor enucleated with ESD. An 82‐year‐old woman was referred for treatment of a gastric tumor. Upper gastrointestinal endoscopy revealed a solitary submucosal tumor in the greater curvature of the gastric body. We diagnosed a carcinoid tumor by histological examination of biopsy specimens. Endoscopic ultrasound revealed a hypoechoic mass in the submucosal layer. Neither lymph node nor liver metastasis was recognized. The serum gastrin level was normal, and this tumor was classified as a type III (sporadic) carcinoid tumor. Endoscopic resection was decided on considering her age, general status, and wishes. We used ESD techniques, because the tumor was too large to be resected by conventional endoscopic mucosal resection. En bloc resection was performed. Histological examination of the 13 × 19 × 11 mm resected specimen showed that the cut end was free of tumor cells. Type III carcinoid tumor is usually treated by surgical resection with lymph node dissection. However, in high‐risk elderly patients we consider ESD to be a therapeutic option for local control of gastric carcinoid tumors.     

Gastric cancer with features of submucosal tumor: a case report

A case of stomach carcinoma showing the features of a submucosal tumor (SMT) is reported. The patient was a 65-year-old woman admitted to the Internal Medicine Department with autoimmune hepatitis and complaining of anemia and tarry stools. Endoscopy revealed a submucosal tumor-like lesion with central ulceration. The lesion was the suspected cause of the anemia; therefore, a partial resection of the stomach was performed. The histopathologic examination revealed a mucinous adenocarcinoma (MUC). The tumor extended to the submucosa. Accordingly, a subtotal gastrectomy with regional lymph node dissection was performed. In stomach carcinoma simulating an SMT, generally preoperative diagnosis is important. However, in this patient, surgery was selected as the best treatment.     

Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis

A 61-year-old man was admitted to our hospital because of abdominal pain and an abdominal mass. The patient had anemia and elevated serum alpha-fetoprotein (AFP) (9630ng/mL) and PIVKA-II (91mAU/mL) levels. Roentgenographic examination revealed an extra-gastric tumor in the upper abdomen, and gastroscopy revealed Bormann type 2 gastric cancer in the lower portion of the stomach. The preoperative diagnosis was synchronous gastric cancer and hepatocellular carcinoma (HCC), and surgery was performed. The extra-gastric tumor appeared to be an extra-hepatically growing HCC because the tumor was fed by vessels ramifying from the umbilical portion of the liver. Distal gastrectomy with resection of the extra-gastric tumor was performed, and histological examination of the resected specimen revealed that the gastric cancer was an AFP-producing hepatoid gastric adenocarcinoma and that the extra-gastric tumor was a lymph node metastasis. AFP-producing hepatoid gastric adenocarcinoma tends to metastasize to the regional lymph nodes and form a giant tumor. A giant tumor in the upper abdomen associated with gastric cancer may therefore be a clinical manifestation of AFP-producing hepatoid gastric adenocarcinoma.     

EARLY GASTRIC CANCER WITH WIDESPREAD DUODENAL INVASION WITHIN THE MUCOSA

We report a rare case of early gastric cancer confined to the mucosal layer with extensive duodenal invasion, curatively removed with distal gastrectomy. An 84‐year‐old Japanese woman was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed an irregular nodulated lesion measuring 6.5 x 5.5 cm in the gastric antrum and an aggregation of small nodules in the duodenal bulb. A biopsy specimen showed well‐differentiated adenocarcinoma. The patient underwent distal gastrectomy with partial resection of the duodenal region containing the tumor and regional lymph node dissection, with no complication. Histological examination of the resected tissue confirmed well‐differentiated adenocarcinoma limited to the mucosal layer and without lymph node metastasis. The cancer extended into the duodenum as far as 38 mm distant from the pyloric ring, and the resected margins were free of cancer cells. Gastric cancer located adjacent to the pyloric ring thus has the potential for duodenal invasion, even when tumor invasion is confined to the mucosal layer. In such cases, care should be taken during examinations to detect duodenal invasion, and the distal surgical margin must be negative given sufficient duodenal resection.     

Pure gastric yolk sac tumor that was diagnosed after curative resection: case report and review of literature

We recently experienced an 87-yr-old man with gastric yolk sac tumor. Preoperative diagnosis was poorly differentiated adenocarcinoma in the cardia of stomach without apparent metastasis. A total gastrectomy was performed. The precise histological examination after surgery revealed the tumor was composed of pure gastric yolk sac tumor without adenocarcinomatous components. The surgical margin and the resected lymph nodes were histologically negative for the tumor and a curative resection was performed. Five months after the operation, enlargement of the intraabdominal lymph nodes occurred with elevation of serum alpha fetoprotein (AFP), and the patient died 2 mo later. Gastric yolk sac tumors are very rare, and only six cases of gastric yolk sac tumors have been previously reported in the literature. Five out of six cases are accompanied by components of adenocarcinoma, and our present case is the second report of pure gastric yolk sac tumor to the best of our knowledge.     

Pathology of endoscopic submucosal dissection; how do we interpret?

It is widely accepted that endoscopic submucosal dissection (ESD) is an important treatment option for cases of early gastric carcinoma where the probability of lymph node metastasis is very low. The resected ESD specimens are carefully examined by serial sections at 2 mm intervals, and if pathology reveals submucosal invasion more than 500 μm and/or lymphovascular invasion, or if the resection margin is involved by the tumor, surgery is recommended. In this point of view, thorough pathologic examination and reporting the accurate pathologic diagnosis of ESD specimen is very important. The diagnostic approach and pitfalls in the diagnosis of ESD specimen are reviewed.     

Endoscopic submucosal dissection and surgical treatment for gastrointestinal cancer

Endoscopic submucosal dissection (ESD) is widely usedin Japan as a minimally invasive treatment for earlygastric cancer. The application of ESD has expanded tothe esophagus and colorectum. The indication criteriafor endoscopic resection (ER) are established for eachorgan in Japan. Additional treatment, including surgery with lymph node dissection, is recommended when pathological examinations of resected specimens donot meet the criteria. Repeat ER for locally recurrent gastrointestinal tumors may be difficult because of submucosal fibrosis, and surgical resection is required inthese cases. However, ESD enables complete resectionin 82%-100% of locally recurrent tumors. Transanal endoscopic microsurgery (TEM) is a well-developed sur-gical procedure for the local excision of rectal tumors.ESD may be superior to TEM alone for superficial rectaltumors. Perforation is a major complication of ESD,and it is traditionally treated using salvage laparotomy.However, immediate endoscopic closure followed byadequate intensive treatment may avoid the need forsurgical treatment for perforations that occur during ESD. A second primary tumor in the remnant stomach after gastrectomy or a tumor in the reconstructedorgan after esophageal resection has traditionally required surgical treatment because of the technical difficulty of ER. However, ESD enables complete resectionin 74%-92% of these lesions. Trials of a combination ofESD and laparoscopic surgery for the resection of gastric submucosal tumors or the performance of sentinellymph node biopsy after ESD have been reported, butthe latter procedure requires a careful evaluation of itsclinical feasibility.     

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.     

Ten-year survival after pancreatoduodenectomy for advanced gastric cancer--report of two cases.

We performed pancreatoduodenectomy for 5 patients with gastric cancer, and here we present 2 who have survived for more than 10 years. Patient one had a large antral tumor tightly adherent to the head of the pancreas. Pancreatoduodenectomy with lymph node dissection was performed. Pathologic examination of the resected specimen revealed that the tumor was a well differentiated adenocarcinoma invading the duodenum, but not the pancreas. Patient two had an infrapyloric lymph node metastasis invading not only the pancreatic head, but also the duodenocolic ligament and the transverse mesocolon. Pancreatoduodenectomy and right hemicolectomy with lymph node dissection were performed. Pathological examination of the resected specimen revealed grade III lymph node metastasis, and invasion of the pancreas by the metastatic infrapyloric lymph node. These results indicate that complete resection of tumor by pancreatoduodenectomy may result in a long survival not only for the patients in whom pancreatic invasion and/or lymph node metastasis is limited, but also for some patients with tumor invading the pancreatic parenchyma and/or of grade III lymph node metastasis.     

Lymphatic invasion in small differentiated-type mucosal gastric cancer

Endoscopic resection for early gastric cancer is indicated for patients who are at negligible risk of lymph node metastasis. A 71-year-old female underwent endoscopic resection for a 15-mm differentiated-type mucosal gastric tumor, as recommended in the Japanese treatment guidelines. A histological examination revealed lymphatic invasion. Therefore, we performed laparoscopy-assisted distal gastrectomy and D1+ lymph node dissection. A histological examination detected no.3 lymph node metastasis, but no residual cancer cells were observed at the site of the endoscopic resection. This case is rare as lymphatic invasion and lymph node metastasis are highly unusual in small differentiated-type mucosal gastric cancer. Having experienced this case, we consider that en-bloc endoscopic resection of such lesions is extremely important, as it allows precise histological examinations to be performed, which can determine the necessity of additional treatment.     

Cardiac tamponade due to metastasis from early gastric cancer

We report a case of cardiac tamponade caused by metastasis from early gastric cancer. A 44-year-old woman was detected to have an abnormality of the stomach on barium meal during an annual medical checkup. Gastroendoscopy disclosed superficial depressed gastric lesions, and histopathological examination of biopsy specimens revealed the diagnosis of poorly differentiated adenocarcinoma and signet-ring cell carcinoma. Computed tomography (CT) and ultrasonography (US) revealed no evidence of metastasis. We performed distal gastrectomy with regional lymph node dissection. Histopathological examination revealed poorly differentiated adenocarcinoma and signet-ring cell carcinoma confined to the mucosal layer. Lymphatic invasion was detected only in the mucosal region beneath the tumor; however, lymph node metastasis was found in almost half of dissected lymph nodes. Adjuvant chemotherapy was administered on an outpatient basis with 36 courses of mitomycinC infused (8 mg/day) once every 4 weeks. However, 3 years after the surgery, the patient developed cardiac tamponade due to carcinomatous pericarditis. We performed drainage of the malignant effusion and initiated treatment with S-1 and docetaxel. Although the patient showed some clinical improvement, the patient died 15 months after the occurrence of cardiac tamponade.     

Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: Case series

Epstein-Barr virus(EBV)-associated lymphoepitheliomalike gastric carcinoma(LELC) is characterized by a lower lymph node(LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection(ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 μm in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD.     

Differentiated adenocarcinoma with a gastric phenotype in the stomach: difficulties in clinical and pathological diagnoses

Differentiated-type adenocarcinoma with gastric phenotype of the stomach is rare and is difficult to diagnose both clinically and pathologically. We report a case of differentiated-type adenocarcinoma with a gastric phenotype in the stomach. A 60-year-old Japanese female was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed a granular elevated lesion in the lower body near the lesser curvature and a depressed lesion on the antrum. A biopsy specimen showed benign atrophic mucosa in a granulated lesion and moderately differentiated adenocarcinoma in the depressed lesion. The patient underwent laparoscopy-assisted distal gastrectomy with lymph node dissection. The postoperative course was uneventful. Histological examination of the resected tissue confirmed well-differentiated adenocarcinoma in the granulated lesion and moderately differentiated adenocarcinoma in the depressed lesion, without lymph node metastasis. Both lesions were confined to the mucosa. Since mucin immunohistochemistry revealed MUC5AC-positive staining in the granulated lesion, the final diagnosis was differentiated-type adenocarcinoma with gastric phenotype in the stomach. Despite the high malignant potential, the clinical and pathological diagnoses of gastric-type differentiated adenocarcinoma are often difficult. Mucin immunohistochemistry together with hematoxylin and eosin (HE) staining may be helpful in the pathological diagnosis of this rare disease.     

Confusion and prospects for carcinogenesis of gastric adenoma and dysplasia: What is the correct answer currently?

There are differences in the diagnoses of superficial gastric lesions between Japan and other countries. In Japan, superficial gastric lesions are classified as adenoma or cancer. Conversely, outside Japan, the same lesion is classified as low-grade dysplasia (LGD), high-grade dysplasia, or invasive neoplasia. Gastric carcinogenesis occurs mostly de novo, and the adenoma-carcinoma sequence does not appear to be the main pathway of carcinogenesis. Superficial gastric tumors can be roughly divided into the APC mutation type and the TP53 mutation type, which are mutually exclusive. APC-type tumors have low malignancy and develop into LGD, whereas TP53-type tumors have high malignancy and are considered cancerous even if small. For lesions diagnosed as category 3 or 4 in the Vienna classification, it is desirable to perform complete en bloc resection by endoscopic submucosal dissection followed by staging. If there is lymphovascular or submucosal invasion after mucosal resection, additional surgical treatment of gastrectomy with lymph node dissection is required. In such cases, function-preserving curative gastrectomy guided by sentinel lymph node biopsy may be a good alternative.     

Endoscopic submucosal dissection as a staging measure may not lead to worse prognosis in early gastric cancer patients with additional gastrectomy

BACKGROUND: Endoscopic submucosal dissection is a novel endoluminal technique that enables resection of early stage gastrointestinal malignancies in an en bloc fashion. AIM: To assess whether preceding endoscopic submucosal dissection affected the prognoses of patients who underwent additional gastrectomy with lymph node dissection due to suspicion of nodal metastasis from endoscopic submucosal dissection specimens. PATIENTS AND METHODS: Thirty-one patients with early gastric cancer who underwent gastrectomy after endoscopic submucosal dissection were retrospectively investigated in terms of their survival and tumour recurrence. Additional gastrectomy was performed when histology of the endoscopic submucosal dissection specimens revealed that the tumours did not meet the criteria for node-negative cancers. RESULTS: Twenty-three (74%) and eight (26%) patients had undergone endoscopic submucosal dissection previously due to clinical diagnoses of node-negative cancers and possible node-positive cancers, respectively. Histology of the resected stomachs and lymph nodes revealed residual carcinoma of the stomach in two (6.5%) patients and nodal metastases in four (13%) patients. All patients remain alive without recurrence (median follow-up, 3.4 years; range, 0.6-5.2 years). CONCLUSIONS: Based on the histology of endoscopic submucosal dissection specimens, preceding endoscopic submucosal dissection itself had no negative influence on a patient's prognosis when additional gastrectomy was performed. It may be permissible to resect some early gastric cancers by endoscopic submucosal dissection as a first step to prevent unnecessary gastrectomy, if technically resectable.     

Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection

An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection(ESD) for early gastric cancer(EGC).Two years after the initial ESD, a 0-Ⅱc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum.The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma.ESD was performed for this lesion and en bloc resection with negative margins was achieved.Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer(1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection.Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection.Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD.Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known.The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.     

Long-term survival after extended surgical resection of intrahepatic cholangiocarcinoma with extensive lymph node metastasis

We present a case of long-term survival in a patient that involved intrahepatic cholangiocarcinoma that metastasized to the paraaortic lymph nodes. A 62-year-old man underwent extended left hepatic lobectomy with caudate lobe resection, extrahepatic bile duct resection, portal vein resection and reconstruction, and middle hepatic vein resection and reconstruction with lymph node dissection for a liver tumor that was located in the caudate lobe. Histological examination of the resected specimen revealed moderately differentiated adenocarcinoma compatible with cholangiocarcinoma, and lymph node metastases were found in the area of the hepatoduodenal ligament and the paraaortic region. After surgical resection, recurrence was detected twice in the lymph nodes at the site of the left supraclavicular region. These recurrent tumors were completely eliminated by systemic chemotherapy with cisplatin or mitomycin C. The patient is now doing well 6 years and 5 months after surgical treatment. In this case, there was only one tumor, and the preoperative serum carbohydrate antigen 19-9 level was normal. In addition, heterozygosity was retained at the loci on chromosome 8p. These findings suggested that tumor in the present case was less aggressive, despite the nodal spread. The extensive surgical approach may have contributed to the long-term survival of this patient, while the recurrent tumor was sensitive to antitumoral agents.     

Effectiveness of preoperative chemotherapy for far advanced gastric cancer

We herein report a case in which preoperative chemotherapy with cisplatin and 5-fluorouracil was found to effectively treat far advanced gastric cancer invading the pancreas forming a huge mass with regional and distant lymph node metastases. As a result of this treatment regimen, a potentially curative resection was performed which led to a substantially increased survival. The patient was treated with 10 mg of cisplatin and 1000 mg of 5-fluouracil each day preoperatively. After the continuous administration of these drugs for 28 days, the findings of extensive pancreas invasion and lymph node metastases dramatically disappeared. The tumor could be curatively resected by a total gastrectomy with lymph nodes dissection, combined with a distal pancreatectomy and splenectomy. A histological study of a resected specimen showed some cancer cell infiltration remaining within the muscularis propria with fibrous change. There was no evidence of either pancreas invasion or lymph node metastasis. As a result, postoperative adjuvant chemotherapy was performed, 14 months later lymph nodes recurrence was detected and the patient died 20 months after surgery. Our findings suggest that preoperative chemotherapy may thus be effective for the treatment of gastric cancer by both reducing the tumor burden and prolonging survival.     

Adenocarcinoma arising from heterotopic gastric mucosa in the cervical esophagus and upper thoracic esophagus: two case reports and literature review

Primary adenocarcinoma arising from heterotopic gastric mucosa (HGM) is rare and the clinicopathological characteristics are not well known. We present two cases of esophageal adenocarcinoma arising from HGM with a review of a case series. Case 1 was a 78-year-old woman who underwent a periodic medical examination without complaining of any symptoms. Preoperative evaluation suggested esophageal adenocarcinoma arising from the HGM. The patient was treated with endoscopic submucosal dissection. Definitive pathological diagnosis confirmed adenocarcinoma arising from the HGM. Case 2 was a 70-year-old man who underwent a medical examination after complaining of dysphagia. Preoperative diagnosis suggested esophageal adenocarcinoma; however, its origin was unclear. The patient was treated with surgical resection. Definitive pathological diagnosis revealed adenocarcinoma arising from the HGM. In this article, the authors report the clinicopathological features of esophageal adenocarcinoma arising from HGM that were collected from a literature review and our cases.