Early gastric cancer with Krukenberg tumor and review of cases of intramucosal gastric cancers with Krukenberg tumor

A 47-year-old woman was admitted because of hypermenorrhea. Transvaginal ultrasonography revealed an ovarian tumor and myoma uteri, and total hysterectomy with bilateral salpingo-oophorectomy was performed. Histology revealed signet-ring cell carcinoma in the right ovary. In order to find out the primary site of this tumor, gastroendoscopy was performed after the operation, and showed a IIc lesion in the lower body of the stomach; biopsy specimens showed signet-ring cell carcinoma similar to that in the right ovary. Total gastrectomy revealed that the lesion was an early gastric cancer confined to the mucosa, but there was lymphatic invasion slightly beneath the muscularis mucosa, with regional lymph node metastasis. In the light of a review of the seven cases of early gastric cancer with Krukenberg tumor previously reported, lymphatic metastasis seemed to be the most likely pathway of ovarian metastasis in early gastric cancers.     

A case of Epstein-Barr virus (EBV) associated remnant gastric carcinoma arising 7 years after distal gastrectomy for EBV associated gastric carcinoma]

A 52-year-old man undergoing distal gastrectomy for gastric cancer in July 1998 was found to have a 0-IIa type gastric tumor near EC junction in January 2005. Histological examination showed the tumor was moderately differentiated adenocarcinoma. As the tumor was diagnosed as mucosal cancer, endoscopic mucosal dissection was performed. But pathological findings showed the depth of cancer cell invasion into deep submucosal layer. Then total resection of remnant stomach was performed. Both tumors were diagnosed as EBV-associated carcinoma. It is speculated that the mucosa changing after initial operation would give risk to a new occurrence of EBV-associated remnant gastric carcinoma. And then follow up after operation is important. Although some cases of EBV-associated remnant gastric carcinoma is found for short period after the primary surgery, our case second primary cancer was found 7 year after primary surgery. Long term follow-up by Endoscopy seems to be important.     

Analysis of the prognostic factors for liver metastasis of gastric cancer after hepatic resection: a multi-institutional study of the indications for resection

BACKGROUND/AIMS: The number of reports of hepatic resection for metastatic gastric cancer is very small. The outcome and indications of hepatic resection for metastatic gastric cancer remains unknown. METHODOLOGY: A multi-institutional study was made. Thirty-six patients who underwent a hepatic resection for liver metastasis of gastric cancer with no residual tumor were included in this study. The clinicopathological factors were examined as prognostic factors by multivariate analyses. Thirty patients had recurrence and the recurrence pattern and risk factors for extrahepatic recurrence was examined. RESULTS: The overall survival rate was 64% at 1 year, 43% at 2 years, 26% at 3 years 26% at 5 years, and 26% at 10 years after hepatectomy. Multivariate analysis showed that lymphatic invasion, venous invasion of cancer cells of primary gastric cancer and the number of the liver metastasis (> 3) were independent poor prognostic factors after hepatic resection. The most common recurrence pattern was intrahepatic recurrence in 22 patients (73%). The risk factors for extrahepatic recurrence was serosal invasion, lymph node metastasis of primary gastric cancer, stage, and curability of operation. CONCLUSIONS: Hepatic resection for liver metastasis should be attempted in case primary gastric cancer has neither lymphatic invasion nor venous invasion. The most common recurrent site was the liver. In patients with advanced gastric cancer, having neither serosal invasion nor lymph node metastasis, who underwent a less curative operation, the intra-hepatic recurrence would be expected. Thus, aggressive adjuvant chemotherapy through the hepatic artery may improve the survival after hepatectomy in these patients.     

Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

AIMTo investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED).METHODSWe retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTSSix cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED (positivity, 83.3%), immunohistochemically.CONCLUSIONEven in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.     

Prognostic factors after surgery in patients younger than 50 years old with colorectal adenocarcinoma

BACKGROUND/AIMS: The factors predicting recurrence and survival were evaluated using a computer-generated database to identify the independent predictors of survival of colorectal cancer in patients under 50 years of age. METHODOLOGY: One hundred and two patients under the age of 50 years with colorectal cancer who had been admitted into our hospital during the 20-year period of 1980-1999 were identified from a computer database. The factors possibly predicting recurrence were compared by bivariate analysis and the predictors of long-term survival by both univariate and multivariate analysis. RESULTS: A family history of colorectal cancer was present in 14% of all patients and in 15% of the patients aged under 40 years. Overall 5-year survival after radical resection was 59% and median survival 47 months. The recurrence rate after radical resection was 40%, being 13%, 35%, 55% and 80% in Dukes classes A, B, C and D, respectively. The risk of recurrence was most closely related to lymphatic invasion, vascular invasion and Dukes stage. Kaplan-Meier estimates showed that Dukes stage, grade of tumor, venous invasion, lymphatic invasion, perineural invasion and radicality of resection were the best predictors of survival, but in multivariate analysis only the radicality of operation, venous invasion and tumor grade retained their significance. CONCLUSIONS: Young age is not a poor prognostic marker in colorectal cancer. In addition to radical operation, venous invasion and tumor grade are good predictors of survival in patients under the age of 50 years.     

Occult gastric cancer with distant metastasis proven by random gastric biopsy

Krukenberg tumor, a rare metastatic ovarian tumor arising from gastrointestinal adenocarcinoma mainly, tends to occur in premenopausal females. Finding the origin of a Krukenberg tumor is crucial for determining prognosis. In Eastern countries, the most common origin of Krukenberg tumor is stomach cancer, which is generally diagnosed via endoscopic biopsy to investigate an abnormal mucosal lesion. Here, we describe a case of huge adnexal mass in a 33-year-old woman who presented with abdominal distension. Two independent endoscopic examinations performed by experts in two tertiary university hospitals revealed no abnormal mucosal lesion. The patient was diagnosed with a Krukenberg tumor according to findings from random endoscopic biopsies taken from normal-looking gastric mucosa in our hospital. It is very rare to be diagnosed via a random biopsy in cases where three well-trained endoscopists had not found any mucosal lesion previously. Thus, in this case, random biopsy was helpful in finding the origin of a Krukenberg tumor.     

Les tumeurs de Krukenberg d’origine gastrique (à propos de trois observations)

Introduction and aim of the work

The Krukenberg tumors are defined as bilateral ovarian metastasis of a generally digestive cancer. They are rare and account for 1–2% of the ovarian tumors. We report three observations of Krukenberg tumors.

Patients

The first patient was a 19-year-old young woman admitted for an abdominopelvic mass diagnosed clinically and by ultrasonography. The laparotomy highlighted the presence of two ovarian tumors whose histological study revealed metastasis of a carcinoma of digestive origin. The oesogastric fibroscopy showed an undercardial tumor, the histological study of which was a fairly differentiated adenocarcinoma. Chemotherapy was indicated. The patient died in the second month following the diagnosis. The second case was revealed by an acute peritonitis due to a perforated gastric antral tumor in a 46-year-old woman. The exploration of the pelvis found bilateral ovarian tumors. The histology of the biopsies showed a gastric adenocarcinoma. Because of the deterioration of his general state, the patient had only symptomatic treatment. She was followed up consultation for two months; then lost. The third patient was a 40-year-oldwoman who presented during 5 months epigastric pain. Gastric fibroscopy revealed a carcinoma with independent cells. The CT scan showed two ovarian tumors of respectively 30 and 80 mm. Palliative chemotherapy was indicated.

Conclusion

The Krukenberg tumors are rare; their treatment is palliative and is still not codified. Progress in chemotherapy could ameliorate the prognosis of these tumors that is still dark.     

Prognostic factors of advanced gastric carcinoma without serosal invasion (pT2 gastric carcinoma).

BACKGROUND/AIMS: The purpose of this study was to investigate the prognostic factors of advanced gastric carcinoma without serosal invasion (pT2 gastric carcinoma), for the planning of therapeutic strategy. METHODOLOGY: Prognostic factors were evaluated by univariate and multivariate analysis in a total of 304 curatively resected pT2 gastric carcinoma patients in whom the tumor invaded the muscularis propria or the subserosa. RESULTS: Macroscopic type, depth of invasion, lymph node metastasis and venous invasion were significantly related to outcome, using univariate analysis. Lesions resembling early gastric carcinoma had better prognosis than lesions belonging to one of the Borrmann types. Multivariate analysis (Cox's proportional hazards model) demonstrated that macroscopic type, lymph node metastasis and venous invasion, but not depth of invasion, were significant prognostic factors. CONCLUSIONS: Macroscopic appearance, lymph node metastasis and venous invasion were the important prognostic factors of pT2 gastric carcinoma. Extensive lymph node dissection and aggressive post-operative chemotherapy should be performed, especially in Borrmann type lesions with lymph node metastasis.     

Primary signet-ring cell carcinoma of the colon at early stage： A case report and a review of the literature

A 67-year-old man, who had undergone surgery to resect multiple gastric cancers 4 years ago, visited our hospital for surveillance colonoscopy. Colonoscopy revealed a discolored, 7-mm in diameter, flat-elevated lesion with central depression in the transverse colon near the splenic flexure. Although the findings of endoscopy and barium enema were suggestive of submucosal invasion, the patient chose to undergo endoscopic mucosal resection. Pathological examination of the resected specimen revealed signet-ring cell carcinoma and a positive surgical margin. A second operation was performed, and no residual tumor or metastasis to lymph nodes was found in the resected specimens. Primary colorectal cancers composed of signet-ring cell carcinoma detected and treated at an early stage are extremely rare. We present a case and review the literature.     

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.     

Tumor cell proliferation in early gastric cancer: biological and clinical behavior

BACKGROUND/AIMS: Recently, early gastric cancers without lymph node metastasis have successfully been removed through a simple endoscopic resection. Tumor cell proliferation may be related to the malignant potential of early gastric cancer. The purpose of this study is to prospectively investigate the relationship between the incorporation rate of bromodeoxyuridine (BrdU) into the DNA of dividing cells, and the main biological and clinical early gastric cancer characteristics. METHODOLOGY: Multiple tumor specimens were taken from 27 early gastric cancers and analyzed through anti-BrdU monoclonal antibody. Tumor BrdU labeling index (LI=% positive cells over 2,000 tumor cells) was determined. Early gastric cancers were evaluated in tumor size, mucosal and submucosal involvement, histologic type and grading, lymphatic and venous invasion, and nodal metastasis. RESULTS: BrdU LI was significantly higher in patients with submucosal neoplastic invasion, Pen A Kodama type, tumor vessel invasion and lymph node involvement. Early gastric cancer patients with over 22% BrdU LI showed a significantly higher incidence of submucosal invasion, lymphatic-venous involvement and a reduced survival when compared to patients with medium (12-22%) or low BrdU LI (<12%). CONCLUSIONS: Our results suggest that BrdU LI may be considered a useful indicator of early gastric cancer aggressiveness.     

Sonographic appearance of Krukenberg tumor from gastric carcinoma

Sonographic findings in 16 cases of Krukenberg tumor from gastric carcinoma were analyzed. The patients' ages ranged from 25 to 52 years (mean 42 years). The tumor involved both ovaries in 14 patients with asymmetrical masses in 9 of 14 cases. Ascites was noted in 15 cases. Echogenicity of the tumor varied from solid to predominantly cystic: solid in 8, mixed in 6, and predominantly cystic in 2 cases. Solid masses tended to be smaller than mixed or cystic masses. The primary gastric carcinoma had been diagnosed before emergence of the tumors in only 7 cases. The findings suggest that in relatively young patients with ovarian mass, particularly bilateral tumors, careful evaluation for gastrointestinal tract involvement should be done.     

Prognostic factors of young patients with colon cancer after surgery

AIM: To investigate the prognostic factors of 96 young patients with colon cancer within a cancer center by univariate and multivariate analysis. METHODS: A total of 723 patients with colon cancer were treated surgically during a period of 10 years. Ninty six of them were 40 years old or younger. R0, R1 and R2 operations were performed in 69 (71.9%), 4 (4.1%) and 23 patients (24%), respectively. Left hemicolectomy was performed in 43 patients, right hemicolectomy in 37 patients, transverse colon resection in 9 patients and low anterior resection in 7 patients. Cox multivariate regression analysis was performed to identify predictors of survival. RESULTS: The operation mortality was 0%, 54 patients died within 111 mo after operation due to occurrence or metastases of the tumor. Liver, lung and bone metastases occurred in 3, 1 and 5 patients, respectively. The mean survival time for all patients was 77.9±5.01 mo and the overall 3-, 5-and 10- year survival rates were 66.68%, 58.14% and 46.54%, respectively. In the univariate survival analysis, patient age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastases, liver metastases and TNM stage were found to be predictors of survival in young patients with colon cancer. In the Cox-regression analysis, blood transfusion and lymphatic invasion were determined as independent prognostic factors of survival. CONCLUSIONS: Age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastasis and TNM stage are the predictors of survival in young patients with colon cancer after surgery.     

微血管密度与CD105、CD31在胃癌中的表达及意义

目的探讨胃癌组织中微血管密度（microvessel density,MVD）与CD105、CD31的表达及生物学行为的关系。方法取61例术前未作放、化疗及免疫治疗胃癌病人的外科手术切除标本,采用免疫组织化学技术S-P法检测CD105、CD31的表达,并定量计数胃癌组织微血管。结果胃癌组织中CD105及CD31标记的MVD在与淋巴结转移、肿瘤浸润深度均有显著性差异（P〈0．05）;Kaplan．Meier法分析显示微血管计数CD105〈14个,CD31〈34个（200×）的胃癌病人预后较好,而微血管计数CD105≥14个,CD31≥34个（200×）预后较差。结论胃癌MVD与其生物学行为有关,提示肿瘤血管生成分析和微血管密度计数是评价胃癌预后的一项重要参考指标。     

CD10 Expression in Colorectal Carcinoma Correlates With Liver Metastasis

PURPOSE If it were possible to identify the features of primary colorectal carcinoma that were associated with liver metastasis, these features could be used as predictors of liver metastasis. METHODS From January 1995 to December 1997, 648 consecutive cases of colorectal carcinoma were recorded at the Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. We evaluated clinicopathologic and immunohistochemical factors (age, gender, tumor location, gross type, size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and expression of CD10, MUC2, and human gastric mucin) in 505 of these patients who had undergone resection of T2/T3/T4 colorectal carcinomas to clarify the correlation between these factors and liver metastasis. RESULTS Liver metastases, including unresectable, were detected in 122 patients (24 percent), all of whom had been followed for at least five years. Univariate analysis revealed that liver metastasis was significantly associated with tumor size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and CD10 expression. Multivariate analysis revealed that invasion deeper than the subserosa, venous invasion, lymph-node metastasis, and CD10 expression were significantly associated with liver metastases. CONCLUSIONS CD10 expression in colorectal carcinoma is a good predictor of liver metastasis. Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare, Japan.     

Spontaneous Regression of a Large Hepatocellular Carcinoma with Multiple Lung Metastases

A 75-year-old Japanese man with chronic hepatitis C was found to have a large liver tumor and multiple nodules in the bilateral lungs. We diagnosed the tumor as hepatocellular carcinoma (HCC) with multiple lung metastases based on imaging studies and high titers of HCC tumor markers. Remarkably, without any anticancer treatment or medication, including herbal preparations, the liver tumor decreased in size, and the tumor makers diminished. Moreover, after 1 year, the multiple nodules in the bilateral lungs had disappeared. Fifteen months after the first medical examination, transcatheter arterial chemoembolization (TACE) was performed for the residual HCC. Because local relapse was observed on follow-up computed tomography, a second TACE was performed 13 months after the first one. At 4 years after the second TACE (7 years after the initial medical examination), there was no recurrence of primary or metastatic lesions. Spontaneous regression of HCC is very rare, and its mechanism remains unclear. Understanding the underlying mechanism of this rare phenomenon may offer some hope of finding new therapies, even in advanced metastatic cases.     

Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma

OBJECTIVE: Recent epidemiological studies indicate that there is reduced risk of all digestive carcinomas in patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. Cyclooxygenase (COX) is a target enzyme for NSAIDs. We investigated the role of two isoforms, COX-1 and COX-2, in the development and metastasis of gastric carcinoma. METHODS: Fifteen gastric carcinoma tissue specimens and accompanying adjacent mucosa specimens were obtained from surgical resections. COX-1 and COX-2 protein expression were evaluated using Western blotting analysis, and their relative band densities were semi quantified using standard densitometry scanning techniques. RESULTS: Compared with paired noncancerous specimens, COX-2 was overexpressed in 10 of 15 carcinoma tissue specimens (66.7%). Overall, COX-2 levels in carcinoma tissue were significantly higher. Two early carcinomas (confined to the mucosa and submucosa) and three of 13 advanced carcinomas (extended below the submucosa into the muscular wall) had weak or similar COX-2 expression in paired tissue specimens. COX-2 overexpression in tumors significantly correlated with tumor invasion into the lymphatic vessels in the gastric wall and metastasis to the lymph nodes. Furthermore, the stage grouping in the TNM classification significantly correlated with COX-2 overexpression. In contrast, COX-2 overexpression did not correlate with histopathological grading, surface size, and venous vessel invasion of the tumors. COX-1 levels were similar between paired tissues. CONCLUSION: COX-2 overexpression might enhance lymphatic invasion and metastasis in patients with gastric carcinoma, implicating a poor prognosis. Therefore, the use of COX-2-specific inhibitor to suppress lymphatic metastasis in humans should be investigated.     

体表超声判定胃癌生物学行为的意义

目的：探讨体表超声对胃癌的某些生物学行为判定的价值及临床意义．方法：胃癌患者102例术前进行超声检查并与手术病理进行对比分析．结果：体表超声对胃癌浸润深度及浸润范围的判定与术后病理的符合率分别为80．4%和67．6%．其中对浸润深度T_1-T_4各期判断符合率分别为60%,87．7%,81．4%和100%：对胃壁浸润范围≤6．0cm和＞6．0cm判断符合率分别为79．7%和47．4%,对肝、卵巢转移,腹水及胰腺浸润的诊断符合率均为100%,胃周淋巴结转移的诊断符合率为74．6%．结论：体表超声能判定胃癌的某些生物学行为,为胃癌的术前分期提供重要依据．     

Signet-ring-cell carcinoma of the ampulla of Vater: a case report

We encountered a rare variant of carcinoma of the ampulla of Vater in a 68-year-old man with postprandial abdominal pain and nausea. Ultrasonography and computed tomography showed a dilated common bile duct and main pancreatic duct. At duodenoscopy, the papilla of Vater was enlarged, and biopsy specimens taken from the papilla revealed signet-ring-cell carcinoma. Endoscopic ultrasonography showed a hypoechoic tumor without pancreatic invasion. Pylorus-preserving pancreatoduodenectomy was performed. Histologic examination of resected specimens indicated lymphatic and vascular invasion, but surgical margins were tumor-free. The patient is alive and disease-free 10 months after the operation.     

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.