Clinical usefulness of the immunostaining of the tumor markers in pancreatic cancer.

The effect of the rapid immunostaining of gastrointestinal cancer-associated antigens, CA19-9, CEA, DUPAN2, and CA50 was discussed for intraoperative pathological diagnosis of pancreatic cancer. The method can be completed in only 13 minutes with microwave irradiation to accelerate the incubation of the primary antibody. Only 3 seconds of irradiation at 500 W for fresh-frozen sections produced specific antigen staining of greater intensity than that obtained with longer incubation by the conventional method. Preservation of the tissue structure was satisfactory with minimal nonspecific background staining enabling us to diagnose the intrapancreatic spread of cancer. This method was also applied to intraoperative peritoneal washing cytology. As with frozen section biopsy, the sensitivity of intraoperative cytology is greater than by the conventional staining method, which is able to achieve more precise staging of pancreatic cancers. Our rapid immunoperoxidase staining method on the cryostat section of pancreatic biopsy specimens and on cytology samples provides important information to determine an appropriate operative approach for pancreatic cancer.

Two-dimensional alterations of myenteric plexus in jejunoileal atresia.

PURPOSE: The purpose of this report is to investigate changes in the myenteric plexus associated with the dilated proximal segment of jejunoileal atresia (JA). Two-dimensional morphologic changes in the myenteric nerve plexuses were investigated using whole-mount preparation. METHODS: Proximal (P) and distal (D) intestinal segments from 7 cases with JA and control (C) segments from 5 postmortem neonates were investigated. The circumference of the jejunoileal segments was measured after fixation. Antibodies for protein gene product 9.5 and neurofilament protein were used in whole-mount preparation. The sizes of neural networks were calculated by measuring the longest circular distance in a neural network (x) and the longest longitudinal distance (y), and the width of the internodal strands (i) with a videomicrometer. RESULTS: Median circumference of the segments was 8.5 in P, 2.0 in D, and 2.0 cm in C. The neural networks in P were expanded longitudinally as well as circularly (x = 817.10 microm, y = 561.26, i = 31.04: median) while comparing them to those in D (x = 431.40 microm y = 288.07, i = 26.05) or C (x = 285.03 microm y = 372.20, c = 1113.57, i = 32.39). The nerve plexus was less expanded than the intestinal wall. CONCLUSIONS: Proximal intestinal segments showed a restructuring that resulted in mild hypoplasia of the enteric nerve plexuses in the proximal segments. The less expansion of the myenteric nerve plexus seen in the proximal bowel in infants with JA suggests a histologic basis for the efficacy of tapering or plication of the dilated bowel.

Changing profile of abdominal wall defects in Japan: results of a national survey.

BACKGROUND/PURPOSE: The incidence of gastroschisis has increased over the past 3 decades in a number of countries. To elucidate the Japanese status of anterior abdominal wall defects, the Japanese Society of Pediatric Surgeons conducted a national survey in Japan. METHODS: Information was obtained by sending out a questionnaire to 192 University Hospitals, Children's hospitals, and general hospitals that each had more than 200 beds. The characteristics of the patients including the birth date, birth weight, gestations, rate of associated anomalies, rate of antenatal diagnosis and prognosis, maternal age, gravidity, history of smoking, and drug use were analyzed. RESULTS: The authors obtained answers from 149 institutions, including 1,785 cases of omphalocele and 970 cases of gastroschisis, which were treated between 1975 to 1997. There was a significant increase in the incidence of gastroschisis, from 0.131 in 1975 to 1980, 0.269 in 1981 to 1985, 0.337 in 1986 to 1990, 0.461 in 1991 to 1995 to 0.467 per 10,000 births in 1996 to 1997. The incidence of omphalocele was 0.322 in 1975 to 1980, 0.567 in 1981 to 1985, 0.657 in 1986 to 1990, 0.741 in 1991 to 1995 to 0.626 per 10,000 births in 1996 to 1997, respectively. In the omphalocele group, 43.1% of the mothers were between 25 to 29 years of age, whereas in the gastroschisis group 42.6% of the mothers were 20 to 24 years of age. In the gastroschisis group, the number of primipara mothers was larger than that of multipara mothers. In the omphalocele group, approximately 10% of the mothers smoked during each period, whereas in the gastroschisis group, the percentage of smoking mothers increased chronologically from 12.9% in 1981 to 1985, 18.7% in 1986 to 1990, 23.5% in 1991 to 1995 and 29.3% in 1996 to 1997. A history of drug use by the mother was approximately 10% for both the omphalocele and gastroschisis groups. In the omphalocele group, 55.9% had associated anomalies against 21.8% in the gastroschisis group. Approximately 10% in the omphalocele group and less than 3% in the gastroschisis group showed chromosomal abnormalities. From 1986, a significant number of cases detected antenatally has been observed. CONCLUSIONS: There have been substantial changes in the incidence of anterior abdominal wall defects, particularly regarding gastroschisis in Japan. The reasons for such changes are most likely multifactorial, further epidemiological monitoring is thus called for.

Clinical results of the shallow core-out procedure in thyroglossal duct cyst operation.

PURPOSE: This procedure for thyroglossal duct cyst operation based on pathological studies was first published in the Journal of Pediatric Surgery in 1992. This procedure is similar to Sistrunk's operation except that the core depth of the tongue excision is more shallow (about 5 mm in young children). The purpose of this report is to report and evaluate the clinical results of this operation compared with our earlier operative results. METHODS: Eighty-three patients underwent surgery for thyroglossal duct cyst from 1970 to 1997. They were divided into 3 groups. Group I consisted of 31 patients undergoing Schlange's operation (1970 to 1988). Group II were 18 patients undergoing Sistrunk's operation (1989 to 1990). Group III consisted of 34 patients operated on with the authors' procedure (1991 through 1997). The 3 groups are compared for recurrence rate. RESULTS: Recurrence in group I was 6 of 31 (19.3%), 1 of 18 (5.6%) in group II, and 1 of 34 (2.9%) in group III. The recurrence rate showed a statistically significant difference only between group I and III (P = .033). CONCLUSION: The recurrence rate with our procedure was not higher than that of Sistrunk's operation but was significantly lower than for Schlange's operation.

c-Kit immunoreactive interstitial cells in the human gastrointestinal tract.

c-Kit immunopositive cells are considered to be pacemakers and/or mediators of neurotransmission in the gastrointestinal tract. They also correspond to the interstitial cells of Cajal (ICs) in mice. The normal distribution of c-Kit positive cells and their relation to ICs in the human gastrointestinal tract remain unclear. In this study we examine the distribution of c-Kit positive cells and their ultrastructure in normal human tissue. We then classified them and examined their relationship to ICs. Thirty nine samples of gut from the esophagus to the sigmoid colon from humans (ranging in age from a 16 week old fetus to a 57 year old and without motility disorders), were processed for immunohistochemistry, electronmicroscopy and immuno-electronmicroscopy. c-Kit immunopositive cells were located in the external muscle from the lower esophagus to the sigmoid colon, wherever the external muscle was composed of smooth muscle cells, and they were classified morphologically into two groups. Cells in the first group were mainly spindle-shaped bipolar cells with few branches; these cells ran parallel to nearby smooth muscle. Ultrastructurally, they possessed many intermediate filaments and caveolae. The spindle-shaped cells were present in the esophagus, stomach and small intestine. The second group of cells were located only in the colon, and were multipolar or bipolar cells with numerous branches. Cells in the second group were also rich in caveolae and/or smooth endoplasmic reticulum, but intermediate filaments were not prominent. Although both groups of c-Kit immunopositive cells corresponded to ICs, some ICs in the human gut do not appear to express c-Kit immunoreactivity.

Distribution of c-Kit immunopositive cells in normal human colon and in Hirschsprung's disease.

BACKGROUND: Subpopulations of c-Kit immunopositive cells in the muscle coat of the gastrointestinal tract are considered pacemaker cells and have been investigated in human tissue relating to motility disorder. However, the morphology of c-kit immunopositive cells in intact human tissue is still unclear. METHODS: The authors studied the distribution of c-Kit immunopositive cells in the normal human colon and their cellular configuration by confocal microscopy on whole-mount preparations. The authors then compared them with six cases of Hirschsprung's disease (HD; two of short segment aganglionosis, three of extensive aganglionosis, and one of total aganglionosis). RESULTS: In the normal colon regional differences were found in the distribution of c-Kit immunopositive cells. The population in the muscle layers and at the submucosal border was larger in the anal part than in the oral part. Accumulation of positive cells at the myenteric plexus level was prominent only at the descending colon. In the descending colon of HD the authors could not demonstrate any differences in c-Kit immunopositive cells on aganglionic segments compared with the corresponding area of intact tissue. CONCLUSION: More attention must be paid to these regional differences of distribution, and identical regions of affected and unaffected bowels must be compared when discussing the relation between the abnormality of c-Kit-positive cells and motility disorders including HD.

Thyroglossal duct remnant penetrating the hyoid bone--a case report.

Examination of the thyroglossal duct (TGD) in a senile patient with a thyroglossal duct cyst (TGDC), as well as in children, is very valuable in understanding the pathology of TGDC. The precise anatomy of TGDC was studied in a specimen obtained from a 59-year-old man using three-dimensional reconstruction. The authors found the TGD penetrated the hyoid bone. This pathological evidence has not previously appeared in the literature. Penetration of the hyoid bone by the TGD is the result of a forward growth of the hyoid bone after development of a TGD, which had appeared ventral to the hyoid bone. In this gradual forward growth, the hyoid bone had first started to press against, before eventually engulfing, the TGD.

[Antitumor effect of S-1 and cisplatin treatment against human gastric cancer xenografted in nude mice].

The enhanced effects due to the combined use of oral administration of S-1 and intraperitoneal administration of Cisplatin (CDDP) were examined with gastric cancer xenografts (NUGC 4). S-1, a new anticancer drug, was daily administered at 10 mg/kg (qld x 5 x 3 weeks). 5-FU level in blood was 1 microgram/ml at two hours after the treatment. Antitumor activity was not found in mice with only the CDDP treatment. But antitumor activity by S-1 and daily low-dose (1 mg/kg) or intermittent treatment (5 mg/kg) of CDDP showed better results than daily S-1 treatment. The daily low-dose CDDP treatment showed similar efficacy to the intermittent administration at the same total dose, but the daily low-dose CDDP treatment was better in the light of toxicities. These results suggest that treatment with S-1 and daily low-dose CDDP was effective for gastric cancer.

A case of small cell carcinoma of the stomach.

A case of small cell carcinoma of the stomach is reported. A 53-year-old male was referred to our hospital for elective surgery for gastric cancer. Pre-operative examinations revealed no metastases. Gastrectomy was performed curatively, and there were no gross findings of metastases. Histologically, the tumor was composed of intermediate-sized cells with hyper-chromatic nuclei and scanty cytoplasm. These cells were argyrophilic and positive for chromogranin A. A small portion of the tumor consisted of conventional adenocarcinoma (signet ring cell carcinoma and tubular adenocarcinoma). No lymph node metastasis was observed microscopically. However, 7 months after the operation, splenic and hepatic metastases were detected, and the patient died very soon thereafter. Small cell carcinoma of the stomach is a very rare disease. In literature, only 15 cases have been cured surgically. Among them, only one case had been diagnosed as small cell carcinoma before the operation, which suggests the difficulty of pre-operative diagnosis. The prognosis of this disease is very poor compared with the common type of gastric carcinoma. Considering the poor prognosis of this particular disease, adjuvant chemotherapy might be mandatory in all cases even if surgically curative resection is performed.

The importance of the real-time fluoroscopic intraoperative direct cholangiogram in the laparoscopic cholecystectomy using a new instrument.

BACKGROUND/AIMS: Laparoscopic cholecystectomy (LC) has become an accepted standard operative technique for gallstone treatment worldwide. On the other hand, complications, such as bile duct injuries, have been reported recently with the expansion of indication for LC. Intraoperative cholangiogram (IOC), to minimize the risk of bile duct injury, is now considered to be essential for safe LC. There are disadvantages to IOC such as increased operating time, the possibility of bile duct injury and the difficulties of manipulation. MATERIAL AND METHODS: We have developed a method for real-time fluoroscopic cholangiograms using a new instrument designed by our group for safe LC. First, a round-tip stylet is inserted through a sheath to coax it gently through the spiral valves of the cystic duct. Secondly, the stylet is removed and the cholangiogram catheter is inserted smoothly. Digital C-arm fluoroscopy provides "real-time" imaging of biliary tree. As a result, we became able to obtain a clear cholangiogram easily in a very short time. RESULTS: In the first 136 patients, direct cholangiograms were attempted in 106 cases and successfully completed in 102 cases (96.2%). CONCLUSION: With the development of real-time fluoroscopic intraoperative direct cholangiogram, we are able to cope with bile duct injuries and anomalies, and unsuspected bile duct stones.

Malignant lymphoma of the gastric stump developing 25 years after a distal gastrectomy for benign gastric disease: report of a case.

We report herein the case of a 57-year-old man in whom malignant lymphoma originating in the gastric remnant was confirmed 25 years after a subtotal gastrectomy with Billroth II reconstruction had been performed for gastric ptosis. Gastroscopy revealed an ulcerated tumor on the fornix, and histologic examination of the endoscopic biopsy specimens demonstrated malignant lymphoma. Thus, total gastrectomy with splenectomy, pancreatectomy, and resection of the previously anastomosed jejunal stoma were performed. Histologic examination of the stomach remnant confirmed a diagnosis of B-cell lymphoma of the large-cell type. Although we were unable to study the surgical specimen from the initial operation, the possible relationship between pseudolymphoma and malignant lymphoma has been presented in the literature, which is reviewed following this case report.

Report of a case of benign cystic mesothelioma.

A 32-yr-old man was admitted to Anjo Kosei Hospital for the examination of a cystic peritoneal lesion. This patient had a past medical history significant for an appendectomy. Ultrasonography and computed tomography revealed multiple cysts in the abdominal and pelvic cavities. An exploratory laparotomy was performed on July 1, 1993, revealing numerous thin-walled and translucent cysts in the serosal tissues of the parietal and visceral abdominal peritoneum. These cysts were excised surgically because of clinical suspicion of pseudo-myxoma peritonei. Microscopic examination revealed cysts within the thin cyst wall that were composed of fibrous connective tissue and lined by a single layer of cuboidal or flattened epithelium. Immunohistochemical and ultrastructural studies demonstrated that the lining cells were of mesothelial origin, and the diagnosis was benign cystic mesothelioma. In this paper, we present appropriate diagnostic and treatment procedures for benign cystic mesothelioma and discuss the particular usefulness of using immunohistochemical methods to achieve a histological diagnosis.

Determination of growth fraction index in mammary carcinoma using MIB-1 monoclonal antibody: estimation of whole tumor proliferative potential using biopsy specimens.

We labeled the Ki-67 antigen in mammary carcinomas, using a MIB-1 monoclonal antibody, to evaluate the usefulness of MIB-1 Ki-67 Growth Fraction Indices (GFI; number of Ki-67 positive cells/total number of cells) of biopsy specimens in estimating the proliferative potential of the carcinomas. Formalin-fixed paraffin sections prepared from biopsy material, primary tumors, and axillary lymph nodes of ten invasive mammary carcinomas were chosen for immunohistochemical study. Bound antibody was detected using the avidin-biotin-complex peroxidase method. The GFI of the resected mammary carcinomas was similar to the estimated values based on the GFI of the biopsy specimens. The GFIs of the metastatic nodes in seven of the carcinomas were similar to those of the primary carcinomas, whereas two carcinomas yielded significantly different GFIs in the metastatic foci. These results suggest that the GFI of a mammary carcinoma biopsy specimen may reflect the proliferative ability of the whole carcinoma.

Frantz's tumor (solid and cystic tumor of the pancreas) with liver metastasis: successful treatment and long-term follow-up.

A rare case of Frantz's tumor with liver metastasis is reported. An 11-year-old girl had local resection of a Frantz's tumor in the head of the pancreas. Ten years later, she had a recurrence in the pancreatic head, and two liver metastases were also disclosed at reoperation. Pancreaticoduodenectomy and enucleation of metastatic lesions in the liver were performed. Six years after the second operation, she is well and free of disease. A review of 174 cases of Frantz's tumor disclosed that metastatic disease in the pediatric age group is extremely rare and yet the prognosis is favorable. On the other hand, the outcome in older patients, especially those over 40 years old, is very poor.

Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid.

A case of primary sclerosing cholangitis (PSC) successfully treated with cyclosporine is described. A 65-year-old man who presented with jaundice and anemia was diagnosed as having PSC, accompanied by pancreatic duct abnormalities. Cholangiography and pancreatography showed marked improvements following combined therapy with cyclosporine and methylprednisolone. Cyclosporine seems to be a promising drug for the treatment of patients with PSC. This report reasons that the same disease process affects both the pancreatic ducts and the bile ducts, and that stagnation of pancreatic juice may have a role to play in the pancreatic duct abnormalities.

Expression of blood group-related antigens in normal and malignant pancreatic tissue correlated with genotype of the patient defined by saliva glycoprotein.

BACKGROUND: Seven murine monoclonal antibodies (MoAb) detecting blood group antigens of the Lewis system and their sialylated derivatives were used to define their immunohistochemical distribution in normal and malignant pancreatic tissues. The specific blood group antigens studied included Lewis(a) (Le(a)), Lewisb (Leb), Lewisx (Le(x)), Lewis(y) (Le(y)), sialyl-Lewis(a) (s-Le(a)), sialyl-lacto-N-tetraose (s-LNT), and sialyl-Lewisx (s-Le(x)). METHODS: The expression of these antigens was analyzed by immunoperoxidase technique in pancreatic tissue of patients with (n = 27) and without (n = 19) pancreatic cancer. The genetic background of their secretor status and their Lewis phenotypes were determined by the enzyme-linked immunosorbent assay using purified salivary glycoprotein and MoAb against eight different blood group-related antigens (Le(a), Leb, Le(x), Le(y), H1, H2, A, B2), and the putative genotypes of the patients were classified as follows: SeLe, Sele, seLe, and sele. RESULTS: The following results were obtained: (1) In normal pancreas, Le(a), s-Le(a), s-LNT, and s-Le(x) were expressed in ducts, but their expression was restricted to the luminal side of the cytoplasm (cytoplasmic type with positive polarity). Leb and Le(y) showed similar patterns of expression in ducts and some parts of the acinus. In contrast, Le(x) was absent in most cases. (2) Expression of Leb was observed in normal pancreatic ducts in all 46 patients, regardless of their genotypes. Le(a) and s-Le(a) were not expressed in specimens from patients with the seLe and sele saliva phenotypes. (3) In pancreatic cancer, the following antigens were expressed cytoplasmically in the proportion of cases indicated: Le(a) (78%), Leb (85%), Le(x) (33%), Le(y) (44%), s-Le(a) (78%), s-LNT (89%), and s-Le(x) (85%). They also were detected in the surrounding stroma. This pattern of expression is distinct from that found in normal pancreatic tissue. Patients with Sele and sele genotypes did not express Le(a) or s-Le(a), except in one case. (4) Serum levels of carbohydrate antigen 19-9 (CA 19-9) were not elevated in patients with pancreatic cancer with the Sele and sele genotypes but were elevated in most patients with SeLe and seLe genotypes. CONCLUSION: The overall findings indicate that Lewis-related antigens act as pancreatic tissue-related antigens, depending in part on salivary phenotypes of the patient. With proper antigen selection and the determination of secretor status, these anti-blood group MoAb may be of clinical utility in the diagnosis of pancreatic cancer.

What is the optimal depth for core-out toward the foramen cecum in a thyroglossal duct cyst operation?

The high recurrence rate of thyroglossal duct cyst operations is well documented. Sistrunk's operation is widely accepted as the best procedure to prevent recurrence. Nonetheless, the optimum depth of core-out is still not well documented. We previously reported a standard running pattern of the thyroglossal duct in an anatomical reconstruction study. In more detailed pathological studies, we have tried to determine the optimal depth for core-out toward foramen cecum and the optimal width of the hyoid bone to be resected. The following items were clarified. (1) Double the horizontal distance from midline to the most distant thyroglossal duct in front of the hyoid bone was 2.4 to 9.6 mm. (2) The length of the single duct above the hyoid bone which spreads into many ductuli as it approaches the foramen cecum was about 3 to 5 mm in 2- to 6-year old children. (3) The diameter of the thyroglossal duct at the level of the cranial top of the hyoid bone was 175 to 1,400 microns. Half of the examined cases were less than 500 microns, which may have rendered direct dissection impossible. Based on these studies, we propose: (1) that a minimum of 10 mm of the hyoid bone should be resected, and for the sake of safety, more than 15 mm is preferable; and (2) that the depth of the core-out should be less than 5 mm in young children to avoid the breakdown of the branched ductuli near the foramen cecum.