P53 and MIB-1 expression in gastrointestinal stromal tumor (GIST) of the stomach.

BACKGROUND/AIMS: Routine clinical approaches for evaluating the risk of recurrence in patients with gastrointestinal stromal tumor (GIST) of the stomach have been limited. Some biomolecular markers may yield more useful information in identifying patients having a higher risk of recurrence. In the current retrospective study, we selected MIB-1 and p53 expression as markers to detect at-risk patients. METHODOLOGY: We enrolled 31 gastric GIST patients who underwent gastrectomy at Kagoshima University Hospital. Patients were classified into two groups based on mitosis and tumor diameter. p53 and MIB-1 expression in the primary tumor were detected immunohistochemically. RESULTS: The patients were classified as having a malignant GIST (20 cases), a benign GIST (11 cases). MIB-1 labeling index (LI) varied from 1 to 32% (average 7.8%). The MIB-1 LI for malignant GISTs was 6.3 +/- 6.4%, which was significantly higher than the 3.2 +/- 2.5% observed for benign GISTs (p < 0.01). The 3 patients positive for p53 died as a result of GIST recurrence. CONCLUSIONS: In addition to routine pathological evaluation, expression of p53 and MIB-1 may provide more accurate information regarding the risk of GIST recurrence. Especially, p53 expression of the tumor may indicate patients having a high risk of recurrence.

Clinical merit of subdividing gastric cancer according to invasion of the muscularis propria.

BACKGROUND/AIMS: In TNM classification, carcinoma that has invaded the muscularis propria (mp) and cancer that has invaded the subserosa are both categorized as T2 cancer. However, some mp gastric cancer patients have a good postoperative course, similar to that of early gastric cancer patients. We performed a retrospective analysis of 74 patients with mp gastric cancer, based on the depth of mp invasion. METHODOLOGY: The clinicopathologic features of 74 cases of gastric cancer invading the mp (but no further) were subdivided according to depth of invasion, retrospectively reviewed and compared with surgical features of 165 patients with gastric cancer invading the submucosa (sm gastric cancer). For each tumor, we evaluated the degree of tumor invasion in the mp layer at a magnification of x100, using the section that showed the greatest extent of invasion. The patients were classified into 2 groups: mp1, tumor was limited to the first of the 3 mp layers; mp2, tumor had expanded beyond the first layer. RESULTS: Of the 74 mp gastric cancer patients, 30 were classified as mp1 and 44 were classified as mp2. Patients with mp1 gastric cancer had significantly more macroscopic signs of early gastric cancer, a lower frequency of lymph node metastasis, and a higher rate of operative cure than patients with mp2 gastric cancer. The incidence of lymph node metastasis among mp1 gastric cancer patients was almost equal to that of the 165 sm gastric cancer patients. The 5-year survival rate of mp1 patients was significantly better than that of mp2 patients (p<0.05), but was similar to that of the 165 sm gastric cancer patients (84%) (p<0.05). CONCLUSIONS: There were clear differences in clinical features between the mp1 and mp2 gastric cancer patients. Subdivision of mp gastric cancer according to depth of invasion may enable more precise prognosis and treatment of mp gastric cancer patients. The clinicopathological findings and surgical outcome of the mp1 patients were similar to those of the sm gastric cancer patients. Thus, mp1 patients may require treatment that is similar to treatment administered to patients with early gastric cancer.

Configuration of the straight veins and their intramural anastomoses in the human duodenum: an anatomical study using cast specimens.

BACKGROUND/PURPOSE: There have, hitherto, been no anatomical investigations of the intramural venous system of the duodenum. METHODS: Intramural longitudinal anastomoses of the straight veins in the human duodenum were investigated, using 15 latex resin cast specimens. RESULTS: The venous tree (with a straight vein as the trunk) was developed well, with numerous twigs (venules). We identified two types of longitudinal anastomoses between the straight veins; the direct and plexus-mediated types, with an equal incidence. The direct-type anastomosis was 0.1-0.5 mm in minimum diameter along the course and communicated in almost a straight line between the mother straight veins. In contrast, the plexus-mediated type was regarded as the thickest route (almost 0.1 mm) in the suggested submucosal venular network in the duodenal wall. These two types of anastomoses were distributed almost equally in most of the duodenum, although a relatively lower density was found in the superior portion. On the ventral side of the duodenum, the thicker straight veins had anastomotic branches significantly more frequently than the thinner ones (P = 0.0018). CONCLUSIONS; These results seemed to support the feasibility of Kocher mobilization, as well as the conventional poor preservation of the duodenal venous system during duodenum-preserving surgery. However, because the intramural longitudinal venous anastomoses were limited in number and location, we recommend preservation of the posterior superior pancreaticoduodenal vein and either of the inferior venous arcades, in combination with their concomitant arteries, in exchange for the unavoidable sacrifice of Henle's trunk and the dorsal pancreatic vein.

Infiltration of antitumor immunocytes into the sentinel node in gastric cancer.

The sentinel node (SN) is regarded as the first drainage lymph node, and tumor cells are considered likely to directly affect the SN. However, few reports have identified differences between SNs and non-SNs in cancer patients. Subjects in this study included 27 patients with gastric cancer who underwent curative operation and intraoperative detection of SNs by radioisotope methods. The mean number of SNs was 3.2 (range 1 to 5). Degree of infiltration of natural killer cells, dendritic cells, MIB-1 labeling index, and CD3-zeta expression of lymphocytes in SNs and non-SNs were examined by means of immunohistochemical methods. Degree of infiltration was compared according to depth of invasion and between SNs and non-SNs. Patients with early-stage cancer displayed a greater degree of infiltration of MIB-1 labeling index and CD3-zeta expression than patients with pT2 or pT3 lesions (P<0.05). The MIB-1 labeling index in SNs was significantly lower than that in non-SNs (P<0.05). However, no significant difference was observed in infiltration of natural killer cells, dendritic cells, or CD3-zeta. Morphologic changes of dendritic cells in SNs were not definite. Our results suggest that SNs in gastric cancer might not be suppressed, unlike in breast cancer and melanoma. SN paralysis may depend on tumor- and organ-specific characteristics or exogenous stimulation from the gastric mucosa. Studies in progress will help to identify immunologic paralysis of the SN in various types of cancer. Attention must therefore be paid to organ specificity.

Submucosal territory of the direct lymphatic drainage system to the thoracic duct in the human esophagus.

OBJECTIVE: To investigate how large submucosal drainage territory extends in lymphatic drainage vessels of the esophagus with and without nodal delay and which morphologies are shown when passing through the muscularis propria. METHODS: Submucosal territories of the 22 highly selected direct drainage vessels of 17 esophagi were histologically examined using transverse or sagittal serial sections. Afferent vessels from the esophagus to the subcarinal (6 esophagi) and para-esophageal (5 esophagi) nodes were also examined to identify their courses and drainage territories. RESULTS: We found the direct drainage vessel from the esophagus in 17 of 75 cadavers macroscopically (22.7%). A single submucosal drainage unit gave off 1-3 thick drainage vessels passing through a complete muscle gap of the 2 muscular layers. The unit extended longitudinally for >40 mm but was restricted to the right and/or dorsal quadrants of the esophagus. In contrast, drainage routes with a nodal relay originated from the intermuscular area, except 1 case when the adjacent or concomitant esophageal artery and vein provided the complete muscle gap. CONCLUSIONS: Due to the extended longitudinal but restricted transverse territory of the direct drainage system without a nodal relay and because of the suggested much more frequent occurrence in patients than in cadavers, when superficial carcinoma is found in the dorsal and/or right quadrants of the esophagus, we recommend detailed presurgical investigations of cervical nodes. In contrast, afferents from the esophagus to the first regional node usually seemed to be less responsible for early nodal metastasis than the direct drainage route because of their intermuscular origins.