Shouji Shimoyama

Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer.

Background. No reports have, to date, focused on the relationship between preoperative determination of the depth of invasion and lymph node metastasis. The present study, under the leadership of the Japanese Gastric Cancer Association, was designed to form a basis for decision making in limited treatment for early gastric cancer (EGC). Methods. From eight major hospitals in Japan, 2672 gastric cancers whose preoperative depth of invasion was mucosal(M-cancer), and 6209 EGCs, consisting of 3584 mucosal(m-) and 2625 submucosal(sm-) cancers, were collected by questionnaire. All registered patients underwent gastrectomy with D1 or more extensive lymphadenectomy between 1985 and 1998. Results. The accuracy of preoperative diagnosis of depth of invasion of M-cancers was 80.2% (2144/2672). However, of the total of 2432 M-cancers in which no nodal involvement was observed intraoperatively (N0), histological examination of the resected specimens confirmed that lymph node metastasis was absent in 2353 (96.8%). The frequencies of lymph node metastasis in early gastric, m-, and sm-cancers were 8.9%, 2.5%, and 17.6%, respectively. Node involvement was associated with a higher frequency of undifferentiated than differentiated histology, as well as with greater tumor size. The incidences of lymph node metastasis in m-cancers with a diameter of less than 4 cm, and in sm-cancers with a diameter below 1 cm were 1.3% (37/2837) and 4.9% (4/82), respectively. These metastases rarely extended beyond the first tier. Conclusion. N0 and M-cancers, m-cancers less than 4 cm in diameter, and sm-cancers no larger than 1 cm in diameter may be appropriate indications for limited surgery.

Accuracy of linear-array EUS for preoperative staging of gastric cardia cancer

BACKGROUND The feasibility of a less invasive operation for early stage cancer of the gastric cardia with a low frequency of lymph node involvement has been previously demonstrated by us. Precise discrimination among mucosal, submucosal, and advanced cancers, as well as accurate evaluation of the proximal tumor margin are prerequisites for such stage-specific treatment. EUS is considered the most reliable staging modality. However, there is no EUS study specifically of cardia cancer. METHODS Forty-five patients with gastric cardia cancer who underwent gastrectomy with at least first-tier lymphadenectomy were retrospectively analyzed. The results of preoperative linear-array echoendoscopy (7.5 MHz) with respect to cancer depth, lymph node involvement, and esophageal invasion were compared with postoperative histopathologic findings. RESULTS Overall diagnostic accuracy for depth of invasion was 71%. Sensitivity for T1, T2, and T3 lesions was 100%, 31% and 75%, respectively. Overstaging of T2 cancers was the main diagnostic error. Mucosal (pT1-m) and submucosal (pT1-sm) cancers were correctly discriminated in 81% of patients. Diagnostic accuracy for lymph node involvement was 80%. EUS had positive and negative predictive values of 90% and 80%, respectively, for esophageal invasion. CONCLUSIONS For gastric cardia cancer, the linear-array echoendoscope yielded satisfactory results with respect to depth of invasion, lymph node involvement, and esophageal invasion evaluation. The information obtained is useful to the performance of stage-specific treatment.

Increased angiogenin expression in gastric cancer correlated with cancer progression.

Purpose: The purpose of this study is to elucidate the expression of angiogenin and its previously undemonstrated clinical significance in gastric cancer (GC). Methods: Angiogenin expression was examined immunohistochemically in 21 GC tissues and 21 corresponding normal gastric tissues. The serum concentration was determined by enzyme-linked immunosorbent assay (ELISA) in GC patients preoperatively (n=48) and postoperatively (n=41), in nonneoplastic patients preoperatively (n=23) and postoperatively (n=19), and in 32 healthy volunteers. The amount of angiogenin in the tissue of 21 GC patients was also determined by ELISA. Results: Angiogenin expression was observed in GC cells as well as in some fundic glandular cells and some inflammatory cells. The mean serum concentration in GC patients (407.8 ± 105.2 ng/ml) was significantly higher than that in the nonneoplastic patients (345.7 ± 58.3 ng/ml; P < 0.003) and in the healthy volunteers (333.0 ± 59.3 ng/ml; P < 0.0002). The mean serum angiogenin concentrations were progressively higher in the order T1+T2 (P < 0.04) < T3+T4 (P < 0.0001) < recurrent GC (P < 0.05) subgroups, in the order node-negative (P < 0.05) < node-positive (P < 0.0002) subgroups, and in the order stage I+II (P < 0.02) < stage III and over (P < 0.0005) subgroups as compared with those in the healthy volunteers. These elevated serum angiogenin concentrations in each subgroup were significantly (P < 0.0003) reduced after cancer resection. The amounts of angiogenin in GC tissues correlated significantly with the serum angiogenin concentration (P < 0.01). Conclusions: These results suggest that angiogenin expression is increased in GC and that the increased serum concentration in GC patients correlates with cancer progression.

Results of local resection with regional lymphadenectomy for early gastric cancer.

BACKGROUND In 1999, the authors reported preliminary results of local resection with regional lymphadenectomy(LR) for early gastric cancer. METHODS Twenty-four patients underwent LR until May 2000. Laparoscopic techniques were recently applied. The dissected area for lymphadenectomy depended on the lymphatic flow from the tumor. Local gastric resection was performed with a 2 cm cancer-free margin. Among the 24 patients, 14 who had been followed up for more than 1 year were eligible for the nutritional study, and the nutritional parameters were compared with those for patients undergoing pylorus-preserving gastrectomy (PPG). RESULTS Twenty-two patients not receiving additional gastrectomy needed no restriction of food intake and had neither postgastrectomy symptoms nor recurrence. All nutritional parameters remained stable between the preoperative and the subsequent period. Nutritional superiority of LR over PPG was observed. CONCLUSIONS For selected patients with early gastric cancer, LR can be a treatment of choice to provide a good quality of life.

Concepts, rationale, and current outcomes of less invasive surgical strategies for early gastric cancer: Data from a quarter-century of experience in a single institution

Previously proposed criteria of less invasive surgery for early gastric cancer (EGC) were based mainly on the pathological analyses of the resected specimens; however, preoperative and intraoperative information are also obviously essential for decision making on stage-dependent patient management. Furthermore, most indications and treatment options have not been systematically integrated or evaluated by treatment outcomes. We investigate in this report the rationality of less invasive surgery employed for EGC. Distribution analyses of positive nodes were investigated among 684 patients with primary solitary EGC (379 mucosal and 305 submucosal) who underwent curative resection between 1976 and 2000. Clinicopathological factors highlighted and analyzed included clinical (preoperative and intraoperative) and pathological (postoperative) cancer depth and nodal involvement, gross form, histological type, and maximum cancer diameter, as well as postoperative morbidity and mortality. The scope of lymphadenectomy can be reduced to a modified D1 for clinically mucosal, node-negative, nonpalpable gastric cancer, or for clinically submucosal, node-negative gastric cancer ≤ 1.5 cm for intestinal type, or ≤ 1.0 cm for diffuse type. Otherwise, a modified D2 lymphadenectomy is sufficient. Local resection can be recommended for clinically mucosal, node-negative gastric cancer without apparent ulceration ≤ 4 cm if adjacent lymph nodes are proved cancer negative by a frozen section examination. If the gastric cancer has spread beyond the above criteria, a pylorus-preserving gastrectomy (PPG) can be recommended for tumors located in the middle or lower third of the stomach, provided the distal margin of the cancer is at least 4.5 cm from the pyloric ring. The PPG can be accompanied by a modified D1 or a modified D2 lymphadenectomy according to the respective dissection criteria. Results of these less invasive strategies showed reduced morbidity and mortality, as well as no recurrence or cancer-related deaths. These results suggest that each of our criteria for less invasive surgery for EGC is realistic, well stratified, and satisfactory.

Overexpression of intercellular adhesion molecule-1 (ICAM-1) in pancreatic adenocarcinoma in comparison with normal pancreas

To elucidate the role of intercellular adhesion molecules (ICAMs), which has not been well understood in pancreas, we investigated the localization and expression of ICAM-1 by immunohistochemistry and in situ hybridization (ISH) in pancreatic adenocarcinoma and in normal pancreas. The localizations of ICAM-2 and ICAM-3 were also investigated by immunohistochemistry. In normal pancreas, acinar cells, duct epithelial cells, and Langerhans islet cells failed to stain with anti-ICAM-1, anti-ICAM-2, and anti-ICAM-3 antibodies. These cells showed no expression of ICAM-1 mRNA. On the other hand, various percentages of carcinoma cells were stained with anti-ICAM-1 antibody, while no carcinoma cells were stained with anti-ICAM-2 and anti-ICAM-3 antibodies. ICAM-1 mRNA expression was also observed in carcinoma cells, and ICAM-1 mRNA expression was associated with localization of the ICAM-1 protein. These results suggest that ICAM-1 expression is up-regulated in pancreatic adenocarcinoma cells and that ICAM-1 is involved in malignant processes in pancreas.

Gastric cancer with metastasis to the gingiva

The present case report describes a gastric cancer which showed unusual metastasis in the oral region. A 56‐year‐old male patient underwent total gastrectomy and splenectomy due to advanced gastric cancer in the upper third of the stomach. Fifteen months later, he presented with anorexia and gingival swelling of durations of approximately 3 and 1 month, respectively. The gastric tumor was histologically a signet ring cell and a poorly differentiated cancer with a moderate degree of vascular invasion. Biopsy specimens from the gingival tumor revealed a signet ring cell cancer. Other metastatic sites were the brain, limb bones and abdominal lymph nodes. A bone scintigram revealed an abnormal uptake in the limb bones, while it did not exhibit any abnormality in the oral region. Correlation between the histology of the gingival tumor with that of the gastric cancer, as well as the absence of a gingival tumor at the time of prior gastrectomy, led to a diagnosis that the gingival tumor was a metastasis from gastric cancer. Gastric cancer metastasizing to the oral region, either the osseus or the oral soft tissue, is very rare. Although it cannot be proved without an autopsy, negative findings in the mandible by bone scanning in the present case suggest that direct gingival metastasis can be considered, rather than mandibular metastasis involving the gingiva. Hematogenous spread could be a mechanism of metastasis for this unusual tumor.

Studies of 13C-urea breath test for diagnosis of Helicobacter pylori infection in patients after partial gastrectomy.

Background/Aims: Many of the reports on the diagnostic efficacy of the 13C-urea breath test (13C-UBT) for the detection of Helicobacter pylori in the residual stomach have shown negative results. We conducted an evaluation to establish a standardized protocol and an appropriate cutoff value for 13C-UBT in partial gastrectomy patients. Methods: Forty-two patients undergoing partial gastrectomy were included. Three gastric biopsies from the anastomotic site and mid-to-high body were taken at panendoscopy for histology, culture and rapid urease test (RUT). The 13C-UBT protocol included ingestion of 100 mg 13C-urea, use of mouthwash, and the body in a horizontal position on the left side. Six breath samples were taken after ingestion. Results: The Δ13CO2 values were significantly elevated in infected patients at all time points, and values were higher at 20 min and thereafter than at an earlier time point. The sensitivity of 13C-UBT was 96.3% with the cutoff of 2.0‰ at 40 min. The accuracy rates were highest with 13C-UBT, culture, RUT and histological tests, in that order. Conclusion: Forty minutes and a cutoff of 2.0‰ were found to be optimal for the test, with the body position horizontal on the left side. In the present protocol 13C-UBT appears to be a reliable tool with the same accuracy rate as other routine tests in patients with a remnant stomach.

Type-oriented Intraoperative and Adjuvant Chemotherapy and Survival after Curative Resection of Advanced Gastric Cancer

n= 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n= 13); or UFT 600 mg/day (P2 group, n= 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n= 17), H1 (n= 12), and H2 (n= 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.

A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis

Abstract Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse collection of intraperitoneal gelatinous fluid is associated with gelatinous implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic metastasis is extremely rare. In addition, an inguinal mass as an initial presentation is also relatively rare. This is a case report of a PMP patient who had splenic metastasis and showed an inguinal tumor as an initial presentation. A 59‐year‐old female patient, who had undergone bilateral oophorectomy because of a ruptured ovarian mucinous tumor of boderline malignancy 12 years previously, presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed tomography revealed a low density mass in the pelvic cavity and in the inguinal lesion, as well as in the spleen without any diseases around the organ. The preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and appendectomy, as well as left inguinal herniorrhaphy. Histological examinations revealed a splenic metastasis of PMP originating from the ovarian low‐grade mucinous tumor. She received postoperative intraperitoneal lavage as well as chemotherapy, and has survived for over 7 years postoperatively without any evidence of recurrence, as confirmed by repeated follow‐up CT examinations and CEA determination. Splenic metastasis of PMP is extremely rare; this represents only the third reported case of its kind in the literature. Furthermore, it should be noted that an inguinal tumor can sometimes be an initial presentation of PMP.