Hidemi Yamauchi

The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection

To investigate the prognostic factors of pancreatic cancer, a retrospective analysis of 193 patients who underwent curative resection was conducted. Of the 193 patients, 38 (20%) survived for more than 5 years, the 5-year survival rates for stages I, II, III, and IV disease being 41%, 17% 11%, and 6%, respectively. According to a multivariate analysis, lymph node metastasis, intrapancreatic perineural invasion, and portal vein invasion were significant prognostic factors. Subsequently, a subgroup analysis concerning nodal metastasis and intrapancreatic perineural invasion was performed in 126 patients with records of these histological findings. In the group of patients without nodal metastasis, the 5-year survival rate for those without perineural invasion was 75%, whereas that for those with perineural invasion was 29%, the difference in survival of these subgroups being significant (P<0.02). In the group of patients with nodal metastasis, the 5-year survival rate for those without perineural invasion was 17%, while that for those with perineural invasion was 10%. The most favorable 5-year survival of 89% was observed in the subgroup of patients with stage I disease without perineural invasion. Thus, pancreatic adenocarcinoma categorized by the combination of these independent types of biological behavior showed 5-year survival rates ranging from very high to low, indicating that these two factors play an important role in the prognosis of this disease.

Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis

Background: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. Methods: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. Results: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer‐stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. Conclusions: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.

Treatment strategy of limited surgery in the treatment guidelines for gastric cancer in Japan

Surgical practice for gastric cancer in Japan is based on the Gastric Cancer Treatment Guidelines issued in 2001 by the Japanese Gastric Cancer Association. These recommendations list options for treatment of each stage of cancer, with clear distinctions between interventions recommended for routine use and those that should be confined to trial settings until further evidence for their curative potential becomes available. In this review, we discuss standard surgery, local resection, segmental resection, and pylorus-preserving gastrectomy (PPG) as examples of limited resection and describe in detail the indications for limited lymph-node dissection in cases of early-stage gastric cancer. At present, evidence does not support the conclusion that limited surgery is effective for local resection or for improving quality of life. Thus, use of limited surgery should be considered an experimental approach both in Japan and the West. We conclude that surgeons who are familiar with the criteria for selecting surgical procedures should decide on a case-by-case basis which technique is most appropriate. Choices should be made with consideration of the stage of the cancer, invasiveness of the surgical procedure, and the patients history. For all procedures, the patient must give informed consent and the surgeons must accurately assess the success of the operation after surgery.

Metastatic breast carcinoma masquerading as primary colon cancer

TO THE EDITOR: Breast cancer is the most common malignancy and the fifth most common fatal malignancy in women in Japan. With earlier age and stage at presentation, the survival rate is expected to increase. Long-term survivors of breast cancer are at risk for developing metastatic tumors, even after a prolonged disease-free interval (1). The most common sites of metastatic tumors are the bones, lungs, central nervous system, and liver (2). Metastasis to the colon is rare, but breast cancer is one of the malignancies of epithelial origin that is known to spread to the lower bowel (3). Colonic metastasis from a primary breast cancer can mimic primary colon cancer and may present perplexing diagnostic problems. For proper management, it is important to differentiate metastatic breast cancer from a potentially surgically resectable primary colon cancer. Here we present a case of breast carcinoma that metastasized to the ascending colon. A 57-yr-old woman underwent right modified radical mastectomy and axillary dissection in 1989 for invasive ductal carcinoma, stage I. Adjuvant chemotherapy was not administered postoperatively. She was followed at 2-wk intervals and was treated with tamoxifen at a dosage of 10 mg p.o. b.i.d. for 2 yr. On routine follow-up examination in 1991, a recurrent tumor was found in her chest wall. Physical examination revealed a mass of 1.5 cm in diameter on the right chest wall. Extirpation of the tumor was performed, and the patient was again administered tamoxifen. Her initial response was good, but a tumor developed again on the right chest wall in 1995. The tumor, measuring 8 3 7 cm, was firm and was fixed to the chest wall. Fine-needle aspiration samples from the lesion confirmed that it was metastatic breast cancer. Resection of the tumor together with the major and minor pectoral muscles was performed. One month after the operation, radiotherapy was started. A total dose of 50 Gy in 20 fractions was delivered to the chest wall over a period of 30 days. After radiotherapy, CEF (cyclophosphamide, epirubicin, and 5-fluorouracil) therapy was performed. In April 1999, bone metastatic tumors were found in the third to fifth cervical vertebrae and in the left first rib. A dose of 40 Gy of radiation was delivered to the cervical spine and 48 Gy to the rib; then chemotherapy using mitomycin, methotrexate, vincristin, and cyclophosphamide was performed. In a routine follow-up examination performed in December 1999, the patient was found to be asymptomatic. No recurrent disease was found in her chest; however, an abdominal CT scan showed marked ascending colon thickening. A double-contrast barium enema examination demonstrated severe stenosis with rigidity and stiffening of the ascending colon (Fig. 1). The contour deformity seemed to be that of a submucosal or serosal impressive lesion with a focal apple core stenotic lesion. Endoscopy of the ascending colon showed thickened nodular folds with intact mucosa, edema, and slight stenosis due to submucosal tumor growth. The results of examination of biopsy specimens suggested metastatic breast cancer to the ascending colon. The patient was then referred for surgery. At operation, the ascending colon and transverse mesocolon were found to be thickened and indurated as if involved by a diffuse infiltrating process. Ascites was observed in the Douglas pouch. Histological examination revealed that carinoma cells were positive in ascites. Involvement of the peritoneal tissues was diffuse and infiltrating in nature. The

Pyogenic liver abscesses secondary to carcinoma of the sigmoid colon: a case report and clinical features of 20 cases in Japan.

We report a case of liver abscesses associated with sigmoid colon cancer in an 81-yearold woman. The patient was referred to our hospital because of a tumorous lesion of the sigmoid colon. Five days before the scheduled operation, she presented abdominal pain, fever and chill. Imaging scans revealed multiple liver abscesses in both lobes, which were successfully treated with intravenously administered antibiotics. Two weeks later, the patient underwent laparoscopic-assisted sigmoidectomy. Nineteen cases of liver abscess associated with colonic cancer have been reported during the past ten years in Japan, and we report the clinical features of these cases in this paper. An aggressive search for the underlying cause of pyogenic liver abscess should be an integral part of the definitive treatment of this disease.

Morphological and immunohistochemical changes in intestinal mucosa and PYY release following total colectomy with ileal pouch-anal anastomosis in dogs.

Other studies have shown that both morphologicaland functional adaptation occur in the ileal mucosaafter total colectomy and may be mediated by humoralfactors. To elucidate the participation of peptide YY (PYY) in intestinal adaptation after totalproctocolectomy with ileal pouch-anal anastomosis(IPAA), changes in the number of PYY-containing cellsand in histological appearance in the intestinal mucosa, especially in the mucosa of ileal pouch, wereinvestigated in dogs. We further examined changes inpostprandial PYY release in relation to those inPYY-containing cells. Ten adult beagle dogs underwent IPAA. Before and 2, 6, and 12 months aftersurgery, a test meal was given, and blood samples weretaken from a foreleg vein at intervals for 3 hr formeasurements of plasma PYY concentration byradioimmunoassay. Before and one year after surgery,morphological studies of the intestinal mucosa wereperformed using parameters such as villous height (VH),mucosal thickness (MT), and villous index (VI).Immunohistochemical studies of PYY were also done in the intestinalmucosa. Both fasting and postprandial plasma PYY levelswere reduced to half of the preoperative levels at twomonths after surgery. Thereafter, postprandial levels approached preoperative concentrations,while fasting levels remained unchanged. VH, MT, and VIwere significantly smaller in the ileal pouch than inthe ileal end of the controls. The MT of the ileal pouch was similar to that of the colon.PYY-containing cells in the mucosa of the ileal pouchwere distributed more densely than those in the ilealend, similar to those in the colon of the controls. It was concluded that after IPAA, the pouchmucosa gradually changed to resemble the colonic mucosanot only in histological appearance but also in thepopulation of PYY-containing cells. It is therefore considered that colonic transformation of theilealpouch mucosa is closely related to the increase inthe number of PYY-containing cells and the steadyrecovery of postprandial PYY secretion.

Early carcinoma of the gallbladder

SummaryTwenty five curatively operated patients with carcinoma of the gallbladder were studied to determine the early stage of this cancer according to the depth of invasion. Patients with cancer invasion limited to the proper muscle layer, should be designated as cases with early cancer of the gallbladder and in these cases, metastasis or further invasion was rare and a good postoperative survival rate was obtained. However, if the early cancer was of the nodular or infiltrative type macroscopically, and of tubular adenocarcinoma or adenosquamous carcinoma histologically, the chances of long-term postoperative survival were poor. Based upon our results, it is suggested that extended cholecystectomy should be performed even in patients with early gallbladder cancer.

Exacerbation of acute pancreatitis in the presence of chronic liver injury in rats, with special reference to therapeutic efficacy of prostaglandin E1.

The pathophysiology of acute pancreatitis accompanied by chronic liver injury, and the therapeutic efficacy of prostaglandin (PG)E1 were studied experimentally in rats. Chronic liver injury was produced by subcutaneous administration of CCl4. Acute pancreatitis was induced by the closed duodenal loop (CDL) method, immediately after which PGE1 (60 ng/kg/min) was infused intravenously via the jugular vein. Serum levels of amylase, alpha2-macroglobulin-trypsin complex (alpha2M-TRY), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were determined before and at 3 and 6 h after the onset of acute pancreatitis. Rats without administration of CCl4 served as controls. Serum amylase levels were lower in the liver injury (LI) group than in the normal liver (NL) group at 3 and 6 h. PGE1 had no effect on amylase levels in either group. Serum alpha2M-TRY levels were similar in the two groups at 3 h, but significantly higher in LI than in NL at 6 h. PGE1 tended to decrease alpha2M-TRY levels only in LI. Serum CRP levels were significantly more elevated in LI than in NL at 0, 3, and 6 h. PGE1 decreased CRP levels only in LI. Serum TNF-alpha concentrations were higher in LI, especially at 6 h. PGE1 reduced TNF-alpha levels in LI. Pancreatitis severity scores were significantly higher in LI. PGE1 significantly decreased the severity scores only in LI. Fat necrosis scores were significantly lower in LI. Histologically, interstitial edema was much more prominent in NL than in LI, whereas interstitial hemorrhage was more severe in LI at 3 and 6 h. PGE1 lessened the hemorrhage in LI. The extent of both vacuolization and necrosis of acinar cells was similar for both groups and tended to be improved by PGE1. It is concluded that acute pancreatitis becomes much more serious in the presence of chronic liver injury, and that PGE1 can ameliorate the exacerbated lesions, probably by improvements in blood flow through the pancreatic tissue.

Peripapillary duodenal diverticulum and biliary tract diseases

The relationship between peripapillary duodenal diverticulum and benign biliary tract disease was studied. Peripapillary duodenal diverticulum could be classified pathophysiologically into three types. Type I represents the disease not directly affecting the biliary tract. Type II shows the elevation of bile duct pressure directly caused by intraduodenal pressure loading. Type III includes patients in whom the diverticulum is small and is prone to cause papillitis or mechanical stimulation. This, then, may lead to organic changes in Oddis sphincter and possibly to biliary tract disorders. In our patients, many cases of peripapillary duodenal diverticulum were associated with calcium bilirubinate stones, indicating that a peripapillary duodenal diverticulum is likely to lead to bile stagnation and ascending infection of the biliary tract and thus cause formation of calcium bilirubinate stones. Based on findings in this study, we want to emphasize that Type II peripapillary duodenal diverticulum should be surgically treated.

Clinicopathologic Prognostic Features in Patients with Gastric Cancer Associated with Esophageal or Duodenal Invasion

BACKGROUND We evaluated the influence of several clinicopathologic variables on 5-year survival of patients with gastric cancer associated with esophageal or duodenal invasion, and determined the significance of resection line involvement. PATIENTS AND METHODS A review of the database for gastric adenocarcinoma at Sendai National Hospital between January 1985 and December 1995 identified 923 patients who underwent gastric cancer resection. Of these patients, 37 were reported to have tumour infiltration of the esophagus or duodenum on histological examination of the resected specimens. Univariate and multivariate analyses of patients with esophageal or duodenal invasion were performed to evaluate the prognostic significance of clinicopathologic features. Then the patients were divided into two groups based on the results of microscopic examination: a tumour wedge-positive group for resection margins of less than 5 mm in width and a tumour wedge-negative group for resection margins of more than 5 mm in width. There were 8 patients in the narrow (margin-positive) group and 29 patients in the wide margin (margin-negative) group, respectively. RESULTS Univariate analysis revealed that the significant prognostic factors were nodal involvement (p=0.0004) and gross type (p=0.0031). Multivariate analysis of the esophagus or duodenum-invaded cancer cases, however, revealed that only nodal involvement was a significant prognostic factor. There were statistical correlations between these groups (margin-positive and margin-negative groups) and the Borrmann type of tumour and tumour size. The survival rate was worse in patients with tumour line involvement. CONCLUSIONS Multivariate analysis revealed that the prognosis of patients with esophageal or duodenal invasion was affected only by nodal involvement independently. The risk of surgical margin involvement was high in cases of a large Borrmann type-4 tumour and infiltrative carcinoma.