Pathological appearance of the stomach after endoscopic mucosal resection for early gastric cancer

BACKGROUND: The pathological findings of the resected stomach after endoscopic mucosal resection (EMR) for early gastric cancer were reviewed. EMR was indicated when a lesion consisting of well or moderately differentiated adenocarcinoma had a diameter of less than 2 cm. METHODS: Of 39 patients with early gastric cancer were treated with EMR between 1990 and 1995, 11 required additional surgery. RESULTS: Malignant tissue in the gastric wall was completely removed in four patients, while cancer cells remained in the mucosa adjacent to the scar in five and infiltrated into the submucosa in two. Most of these residual cancers were characterized by a lesion with a diameter exceeding 15 mm and by the location in the body or cardia of the stomach. Lymph node metastases were observed in one patient whose carcinoma invaded the deeper submucosal layer. Assessment of the depth of entire invasion from the endoscopically-resected specimen was correct for six of 11 patients. CONCLUSION: Gastric carcinomas to be resected by EMR should be smaller, especially if located in the body or cardia. Accurate diagnosis of the width and depth of invasion is indispensable before proceeding to EMR. Surgery may be the treatment of choice when there is submucosal invasion.     

Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion

PURPOSE: The aim of this study was to evaluate the role of histopathology of biopsy specimens in predicting depth of infiltration in early colorectal carcinomas before treatment. METHODS: Early colorectal carcinomas that had been resected surgically or endoscopically between 1984 and 1995 were analyzed. Histopathologic findings, including differentiation of adenocarcinoma and a desmoplastic response were investigated. RESULTS: One hundred nine early colorectal carcinomas consisted of 73 lesions of carcinoma in situ, 13 submucosal carcinomas with minimum invasion, 8 lesions with moderate invasion, and 15 lesions with deep invasion. Of 73 carcinoma in situ lesions, 72 (approximately 99 percent) showed well-differentiated adenocarcinomas and no desmoplastic response. Twelve (92 percent) of 13 submucosal carcinomas with minimum invasion also revealed well-differentiated adenocarcinoma without a desmoplastic response. Sixty-three percent (5/8) of lesions with moderate invasion revealed well-differentiated adenocarcinoma. None of the lesions had a desmoplastic response. Among lesions with deep invasion, 73 percent (11/15) demonstrated moderately differentiated adenocarcinoma, and 11 lesions had a prominent desmoplastic response (73 percent; P < 0.01). CONCLUSIONS: These results suggest that if histopathologic findings of biopsy specimens taken from them before treatment demonstrated adenocarcinoma associated with a desmoplastic response, the lesions had at least deep invasion carcinomas. These lesions should be resected surgically. Submucosal carcinomas with minimum invasion, which have no desmoplastic response, could be treated endoscopically.     

Multidrug-resistant tuberculosis. 4. Treatment and prognosis of multidrug-resistant tuberculosis

Mucinous gastric carcinoma is a rare pathologic subtype of gastric adenocarcinoma. Whether the mucin behaves aggressively as in mucinous colorectal carcinoma is still controversial. Most mucinous gastric carcinomas are diagnosed from surgical specimens. The mucinous gastric carcinoma in this case report was discovered preoperatively according to its characteristic presentation. An upper gastrointestinal endoscopic examination showed a round protruding tumor of greater than 4 cm in size on the mid-body of the stomach; it had an uneven, friable and shiny surface. The surface was coated with a sticky layer of mucin-like substance, which persisted even after the aspiration of the gastric juice. Endoscopic ultrasonography (EUS) revealed a large heterogeneous hyperechoic tumor mass, originating from the mucosal and submucosal layers, on the body of the stomach. The mass was covered with a thick layer of hypoechoic amorphous substance. Hence, a mucin-producing tumor was suspected. Subsequent surgical biopsy proved the mass to be a moderately differentiated mucinous adenocarcinoma. This case illustrates the first endoscopic ultrasonographic report of an intraluminal mucin pool as a hypoechoic substance, which is quite different from the hyperechoic presentation of intramural mucin lakes. In preoperative evaluation, EUS is not only important for determining the depth of tumor invasion, but it is also useful in differentiating mucinous gastric carcinoma from nonmucinous gastric carcinoma.     

Apoptosis in labial salivary glands from Sj?gren''s syndrome (SS) patients: comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients

Patients with solitary rectal ulcer syndrome (SRUS) frequently present with a mass that can be misinterpreted as cancer. In contrast, the occurrence and characteristics of SRUS-like histopathology produced by underlying malignancy have not been reported in detail. We report seven patients whose rectal mass that was induced by infiltrating carcinoma showed only histopathologic changes of SRUS on initial mucosal biopsy specimens. Carcinoma was evident in subsequent specimens after one to five repeat biopsies with delay in diagnosis from 1 week to 18 months in six patients. In one patient, infiltrating carcinoma was suggested on the first biopsy specimen by immunohistochemistry for cytokeratin. Three of the patients had primary rectal adenocarcinoma, two had metastatic carcinoma from stomach or ovary, and two had direct invasion of anal squamous cell carcinoma or prostatic adenocarcinoma. We conclude that the histopathology of SRUS may occasionally represent a characteristic but nonspecific mucosal reactive change to a deeper seated malignancy. The terminology "solitary rectal ulcer syndrome/mucosal prolapse changes" with a cautionary note may be useful for reporting biopsy results to emphasize the possibility of underlying primary or metastatic malignancy in the differential diagnosis.     

Moderately differentiated adenocarcinoma of the rectum: a case report of remarkable response to preoperative administration of FT suppository]

A 50-year-old man with moderately differentiated adenocarcinoma of the rectum was operated upon following preoperative administration of FT suppository. Digital examination, colonoscopy, and barium enema showed an elevated lesion with central ulcer of the rectum. Microscopically, the biopsy specimen demonstrated moderately differentiated adenocarcinoma. FT suppository (1,500 mg/day for 52 days, total 78 g) was administered on an outpatient basis. Rectal amputation including lymph node dissection was performed. The tumor markedly reduced in size and changed into a small ulcer in the resected specimen. Microscopically, the tumor degenerated and changed into xanthogranulomatous tissue with foamy histiocytes. Only two tubules of degenerated adenocarcinoma remained. FT suppository for rectal cancer is considered to be safe and effective.     

A case report of resected primary duodenal carcinoma associated with early gastric cancer and cumulative results at 21 institutions in Japan

A case of primary duodenal carcinoma simultaneously associated with an early gastric cancer is reported. A 72-year-old woman complaining of appetite loss and nausea was admitted in June 1988. Endoscopic examination showed an ulcerative lesion in the angle of the stomach and a Borrmann type 2 tumor in the bulb of the duodenum. Both lesions were revealed to be adenocarcinomas by histological examination of obtained biopsy specimens. Synchronous carcinoma was diagnosed and pancreatoduodenectomy and lymph node dissection were performed. The primary tumor of the duodenum was histologically a moderately differentiated adenocarcinoma, and the gastric cancer was a tumor limited to the mucosa. Metastasis was recognized in a regional lymph node (No. 14A). There has been no recurrence during the 4-year postoperative follow-up period. This result suggests that pancreatoduodenectomy with systematic regional lymph node dissection can greatly contribute to prolonging the survival of patients with advanced duodenal cancer. This case is very rare, in that curative operation was performed for a primary duodenal carcinoma simultaneously associated with an early gastric cancer.     

Application and limitation of neoadjuvant hormonal therapy for prostate cancer

Of 156 patients, 111 (clinical stage T1a-b; 21, T1c; 17, T2a-b; 36, T2c; 27, T3; 10) immediately underwent radical prostatectomy (surgery group), and 45 (clinical stage T1a-b; 8, T1c; 4, T2a-b; 10, T2c; 9, T3; 14) received neoadjuvant hormonal therapy (NHT group). NHT offered probability of increasing organ-confined cancer(OCC; pathological stage pT2 or lower N0M0) in the following group, which contains (a) patients who had moderately differentiated adenocarcinoma in the biopsy specimen and T2b or lower diseases, and (b) those who had well differentiated adenocarcinoma, T2c diseases and PSA levels of 10 ng/ml or higher, referred to as "OCC suitable criteria". Of 156 patients, 51 (33%) met OCC suitable criteria. In those cases, the proportion of OCC in NHT group was significantly higher than that in surgery group (11/12 (92%) vs. 16/39 (41%), p = 0.002). NHT is useful for increasing OCC in patients who meet OCC suitable criteria.     

Tumor recurrence following resection for early gastric carcinoma and its implications for a policy of limited resection

Some patients suffer postoperative recurrence after curative resection of early gastric carcinoma. This study reviewed consecutive patients with a single primary lesion and analyzed the relation between the pathologic findings and recurrence of early gastric carcinomas for determining indications for limited surgery. Among the 1585 consecutive patients with a solitary primary lesion of an early gastric carcinoma who had undergone curative surgery between 1963 and 1989 at one general hospital, pathologic findings relating to recurrence were analyzed according to Japan's General Rules for Gastric Cancer Study in Surgery and Pathology. Of these carcinomas, mucosal carcinomas comprised 701 (44.2%) and submucosal ones 884 (55.8%). The total recurrence rate in this series was 1.0%. Submucosal carcinomas (1.6%) were significantly (p < 0.02) more recurrent than mucosal ones (0.29%). Of the 16 patients with recurrence, 10 (62.5%) died within 5 years after surgery, frequently because of blood-borne metastasis. Macroscopically elevated components, the degree of histologic differentiation, and lymph node metastasis significantly contributed to the postoperative recurrence. After detailed analysis of submucosal carcinomas, it is strongly suspected that carcinomas with a macroscopically elevated component were significantly associated with nodal involvement and microvessel invasion, and that these abnormalities lead to recurrence. Among the early gastric carcinomas, differentiated submucosal carcinomas with a macroscopically elevated component, lymph node metastasis, or both have the most potential of recurrence after surgery. Mucosal carcinomas must be restricted to limited surgery, but, blood-borne metastasis should be carefully avoided.     

Gastric carcinoma resected 95 months after being diagnosed: report of a case

It is usually assumed that patients with gastric carcinoma will almost certainly die within 5 years if they do not receive treatment. We report herein a rare case of curative gastrectomy being performed 95 months after gastric carcinoma was diagnosed. A 37-year-old Japanese man had an upper gastrointestinal endoscopy with biopsy which revealed moderately differentiated adenocarcinoma of the stomach. This was diagnosed as type IIc early gastric carcinoma with ulceration but he refused surgery. At 45 years of age, 95 months later, he presented to our hospital with melena, at which time lesions in an identical location had enlarged to Borrmann type 3 advanced gastric carcinoma. Thus, a total gastrectomy with regional lymph node dissection was performed. Although there was no liver or peritoneal metastasis, the regional lymph nodes were involved; however, the patient recovered well and is still alive without any further recurrence roughly 4 years postoperatively. The natural history of gastric carcinoma and the malignant cycle are discussed following the presentation of this case.     

T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect

Prostate cancer screening and early detection efforts have resulted in the identification of smaller volume carcinomas of the prostate. We evaluated the diagnostic features of minimal (< 1 mm) carcinoma in sextant needle biopsy specimens of the prostate and in follow-up analyzed the features of the corresponding carcinomas in the whole gland. We reviewed specimens from 50 consecutive patients who had minimal carcinoma in needle biopsy tissue and who had undergone radical prostatectomy. Histologic grade, tumor size, pathologic stage, and margin status of the 50 carcinomas in the whole gland in which the carcinoma size was minimal in the sextant needle biopsy specimen were compared with those of 50 carcinomas in the whole gland in which carcinoma size was greater than 1 mm in the needle biopsy specimen. The most common morphologic features of these minimal carcinomas were nucleomegaly (96%), infiltrative growth pattern (88%), intraluminal secretions (78%), prominent nucleoli (64%), associated high-grade prostatic intraepithelial neoplasia (40%), amphophilic cytoplasm (36%), hyperchromatic nuclei (30%), and intraluminal crystalloids (22%). Perineural invasion (2%), collagenous micronodules (2%) and mitotic figures (2%) were uncommon. The mean tumor volume in the whole gland of carcinomas corresponding to minimal carcinoma in a needle biopsy specimen was significantly smaller (P=.029) at 1.1 mL than it was in carcinomas with tumor greater than 1 mm in the needle biopsy specimen at 1.6 mL, but other pathologic features of carcinoma in the whole gland were not significantly different. In conclusion, a constellation of morphologic attributes is important for establishment of a diagnosis of minimal carcinoma of the prostate in needle biopsy specimen. Most (82%) of the corresponding prostate cancers in the whole gland were pathologically significant.     

Disseminated carcinomatosis of the bone marrow occurring 11 years after subtotal gastrectomy for gastric cancer]

A 44-year-old man was admitted to our hospital because of purpura, increased serum alkaline phosphatase, and thrombocytopenia. He had undergone subtotal gastrectomy for gastric cancer 11 years earlier. A biopsy specimen of the bone marrow revealed metastatic mucin-forming, moderately differentiated adenocarcinoma. Because the primary tumor was not detected in any other organ, the gastric cancer the patient was treated for 11 years earlier was suspected as the primary tumor. Microangiopathic hemolytic anemia and disseminated intravascular coagulation developed during the clinical course, and the patient deteriorated despite treatment with anticoagulants. Finally, he died of pulmonary carcinomatous lymphangitis. Autopsy revealed a small number of adenocarcinomatous cells in the lymphoduct of the remaining stomach in spite of its mucosa being intact. We concluded that the bone marrow was infiltrated by cancer cells which originated in the stomach 11 years before. It is unclear why adenocarcinoma cells remained dormant for as long as 11 years in the gastric lymphoduct and bone marrow.     

Histochemistry of mucin secreting components in mucoepidermoid and adenosquamous carcinoma of the oesophagus

AIMS: To determine the direction of differentiation of the mucin secreting components in a rare group of oesophageal tumours--oesophageal squamous cell carcinomas with prominent mucin secreting components (mucoepidermoid carcinomas and adenosquamous carcinomas). METHODS: In a review of 617 cases of primary carcinoma of the oesophagus, 16 cases of squamous cell carcinoma with prominent mucin secreting components were studied using a battery of histochemical techniques. RESULTS: The mucin produced by these tumours was mixed and included a variable content of enzyme labile sialomucin (positive for mucicarmine, periodic acid Schiff, and alcian blue, and sensitive to sialidase digestion and negative for high iron diamine-alcian blue). Retrospective analysis of endoscopic biopsy specimens taken from these tumours showed that mucin was present in five (42%) cases. CONCLUSIONS: The glandular component of this group of tumours histochemically differentiated in the direction of oesophageal glands: examination of the mucin secreting component in squamous cell carcinoma in resected specimens is therefore required for recording the true incidence of this type of tumour.     

Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study

OBJECTIVES: In Barrett's esophagus, early adenocarcinomas are often missed on endoscopic biopsy. We therefore examined the distribution and extent of dysplasia and carcinoma in the resected esophagus for comparison with the preoperative biopsy findings. METHODS: Patients whose endoscopy showed Barrett's esophagus but no visible cancer had four-quadrant esophageal biopsies taken every 2 cm. After resection for high-grade dysplasia or early adenocarcinoma, the esophagus was mapped histologically. RESULTS: Nineteen patients had surgery for high-grade dysplasia; two of them (10.5%) had adenocarcinoma in the resected esophagus. Eleven patients had resection after a biopsy diagnosis of adenocarcinoma or suspicion of adenocarcinoma. Esophagectomy mapping confirmed carcinoma in only five of them. Median surface areas were: total Barrett's esophagus 32 sq cm, low-grade dysplasia 13 sq cm, high-grade dysplasia 1.3 sq cm, adenocarcinoma (seven cases) 1.1 sq cm. CONCLUSIONS: Areas of high-grade dysplasia and microscopic carcinoma in Barrett's esophagus are often small. Biopsy differentiation between these lesions is difficult. A systematic endoscopic biopsy protocol will reduce the chance of missing early malignancy in Barrett's esophagus.     

Prognosis and treatment of bile duct carcinoma

Bile duct carcinomas present a therapeutic challenge because of different histologies, tumor locations, and resectabilities. The goal of our study was to identify prognostic factors to better delineate therapeutic options. Forty patients (30 males and 10 females) diagnosed with bile duct cancer, treated between 1985 and 1996, at Kaiser Permanente Medical Center, Los Angeles were retrospectively reviewed. Three prognostically significant variables were identified: tumor histology, tumor location, and resection. Papillary histology was the most significant determinant of long-term survival. Of six patients with papillary adenocarcinoma, four patients (67%) underwent resection, with all four achieving long-term survival. Lower-third lesions also demonstrated a survival advantage. Four out of 12 (33%) lower-third tumors were resected, with a median survival of 36 months. Irrespective of tumor histology or tumor location, tumor resection always afforded longer survival times than did palliative treatments. A prognostic classification system based on weighted values of significant variables is presented that accurately predicted long-term survival. In conclusion, bile duct tumors in general are incurable, except perhaps for a small subset of patients with papillary adenocarcinoma. Papillary histology is the most significant determinant of ultimate survival and cure. A multifunctional prognostic classification system can be helpful for this perplexing disease.     

Expression of CD44 standard and CD44 variant 6 in human lung cancer

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.9%. In 43 cases of adenocarcinoma, positive staining of CD44 st and CD44 v6 was seen in 2.3% and 4.7% of the cases, respectively. None of 21 small cell carcinomas was positive for CD44 st or CD44 v6. In squamous cell carcinomas, the expression of CD44 st and CD44 v6 was observed at a rate significantly higher than in other histologic type. Most specimens positive for CD44 st stained positively for CD44 v6. Therefore, it seems likely that the CD44 expression observed in squamous cell carcinoma of the lung was a variant CD44 containing the domain encoded by variant exon 6. The expression of CD44 v6 was not related to the clinical stage. Significant association between CD44 v6 and differentiation of squamous cell carcinoma was seen; 2/7 (28.6%) for poorly differentiated, 19/31 (61.3%) for moderately differentiated, and 7/8 (87.5%) for well differentiated squamous cell carcinomas (p = 0.02 by trend test). It was previously reported that CD44 st and CD44 v6 were expressed in both normal bronchial epithelium and squamous cell metaplasia. These results suggest that the expression of CD44 v6 in squamous cell carcinoma of the lung may reflect the immunohistochemical characteristics of the tissue from which such carcinoma emerge.     

Hepatoid adenocarcinoma of the stomach: a case report

A patient with primary gastric carcinoma showing a high level of serum a-fetoprotein (AFP) (368 ng/ml) is described. Subtotal gastrectomy was performed, and a month after surgery the level of serum AFP fell rapidly to within normal limits. Histologically, two types of cells coexisted in the tumor: medullary-type cells resembling trabecular-type hepatocellular carcinoma, and moderately differentiated adenocarcinoma cells. The cells of the former type were arranged mostly in a trabecular pattern with bile granules, but also showed a scirrhous pattern in a restricted area. Immunohistochemistry demonstrated that both types of tumor cells stained positively for AFP. This tumor, which should be classified as a hepatoid adenocarcinoma of the stomach, is of interest because of its rarity, bile secretion (indicating marked differentiation toward a hepatocyte form), and two cellular arrangements-trabecular and scirrhous.     

The cytology of squamous cell carcinomas in domestic animals

A series of 40 tumors with a proven diagnosis of squamous cell carcinoma for which both histology and cytology were available were classified according to their histologic appearance as well differentiated, moderately differentiated, and poorly differentiated. The Romanowsky-stained cytology specimens were reviewed. When available, Papanicolaou-stained smears were included. The cytologic findings for each of the 3 groups are described, and the most significant findings are photographically illustrated.     

Stage IA1 cervical adenocarcinoma: definition and treatment

OBJECTIVE: To propose a definition for stage IA1 cervical adenocarcinoma, based on the International Federation of Gynecology and Obstetrics (FIGO) staging system, and to determine if patients meeting criteria might be candidates for conservative surgery. METHODS: Two hundred women were diagnosed with early-stage cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed, and patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed. RESULTS: Twenty-one patients with microinvasive adenocarcinoma met criteria for FIGO stage IA1 carcinoma of the cervix. The median (range) follow-up was 76 (30-172) months and median (range) patient age was 38 (24-75) years. Definitive treatment included type II or III radical hysterectomy in 16 cases, simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical excision procedure in one case; one patient received adjuvant pelvic radiation. The histologic subtypes were endocervical adenocarcinoma in 18 cases, adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case. There was no evidence of parametrial invasion or lymph node metastases in any patient who had radical surgery, and there were no disease recurrences. CONCLUSION: Patients with microinvasive adenocarcinoma who met criteria for FIGO stage IA1 cervical carcinoma had disease limited to the cervix, and conservative surgery, such as cone biopsy or simple hysterectomy, might offer them definitive treatment.     

Combination chemotherapy with Tegafur. Uracil (UFT), etoposide, adriamycin and cisplatinum (UFT-EAP) for advanced gastric cancer

Thirty-four patients with advanced gastric cancer were treated with combination chemotherapy employing Tegafur-Uracil (UFT), etoposide, Adriamycin, and Cisplatinum (CDDP) (UFT-EAP therapy). An objective partial response was obtained in 16 patients (47%) and the median duration of remission was 12.2 months. The 50% survival time for all 34 patients was 10 months. Patients with moderately or well differentiated adenocarcinoma responded well (13/19, 68%), while those with undifferentiated adenocarcinoma showed a poor response (3/15, 20%). Six responding patients were noted to have no evidence of viable cancer at the primary site by endoscopic biopsy, and underwent gastrectomies. The resected specimens showed complete disappearances of the primary tumors in four patients. The median survival time for the patients receiving gastrectomies was 24 months. The regimen was very well tolerated, apart from moderate bone marrow suppression. Our results suggest that patients with advanced gastric cancer can be effectively treated with UFT-EAP chemotherapy.     

Late follow-up results of operative ankle arthroscopy in patients under local anaesthesia

The clinical diagnoses of nodal status (N) and tumor invasion (T) were performed intraoperatively during 1499 consecutive operations for gastric carcinoma and compared with subsequent pathologic diagnoses. An accurate macroscopic diagnosis of N stage was difficult; overall accuracy was only 56.6%. Intraoperative assessment of T stage (particularly of serosal invasion) was correct for 93.2% of early stages of the disease with invasion confined to the mucosa or submucosa (pT1) when the pathologist assessed the T stage in the resected specimen, for 95.6% of advanced tumors invading the serosa (pT3), but for tumors of an intermediate stage with invasion involving the muscularis propria or the subserosa (pT2) in only 41.9% of cases. Macroscopic overestimation occurred in 58.1% of cases with pT2 tumors, which were characterized by carcinomas in the upper third of the stomach, tumors larger than 5 cm, carcinomas of the ulcerating type, differentiated adenocarcinomas, tumors invading the subserosa, and those accompanied by lymph node metastasis or liver metastasis. The overestimated group had a significantly poorer prognosis than the correctly assessed cases (P < 0.05). Since multivariate logistic regression analysis showed that the significant risk factor related to the inaccurate intraoperative assessment of T stage was tumor size, the error in diagnosis may correlate with a greater degree of tumor spread. Surgeons should decide their therapeutic approach at the time of surgery on the basis of their intraoperative assessment of tumor spread. We recommend extensive surgery followed by adequate chemotherapy when serosal invasion is suspected at surgery.