The flavonols quercetin, rutin and morin in DNA solution: UV-vis dichroic (and mid-infrared) analysis explain the possible association between the biopolymer and a nucleophilic vegetable-dye

Multimodality therapy is used in patients with esophageal cancer because accurate tumor staging is essential to determine whether treatment should be directed toward cure or palliation. Imaging strategies must not only include tumor visualization but also incorporate pretreatment staging as the most important objective. This article reviews the use of CT scans, endoscopic ultrasound, and barium studies in the staging of esophageal cancer.     

Biopsy-negative malignant esophageal stricture: diagnosis by endoscopic ultrasound

Endoscopic ultrasound (EUS) of the esophagus has been used primarily in staging biopsy-proven cancers. Its use as a primary diagnostic modality for esophageal malignancy has not been previously described. We report our recent experience in four patients with dysphagia and endoscopic biopsies negative for malignancy, including one patient with clinical and manometric features suggestive of achalasia. In all cases, EUS revealed a large infiltrating tumor invading through the esophageal wall into the surrounding tissues, and in one case into the aorta. Computed tomography suggested the possibility of a tumor in only one of the cases. Two patients underwent esophagectomy and were found to have adenocarcinoma. Two patients underwent repeat biopsy with alternative aggressive biopsy techniques and were found to have squamous cell carcinoma. We conclude that EUS is useful in the diagnosis of esophageal cancer and should be performed in selected patients with esophageal strictures whose biopsies are negative for malignancy; i.e., those with suspicious endoscopic or radiographic appearance, atypical presentation (e.g., profound weight loss, short duration of symptoms, or advanced age), and failure to respond to treatment.     

Advances in the treatment of esophageal carcinoma

Recent changes in the epidemiology of esophageal carcinoma now recognize adenocarcinoma as the predominant histologic cell type. Barrett's esophagus and dysplasia in this epithelium identify patients who are at risk of developing invasive adenocarcinoma. This neoplasm is not a single entity with a consistently poor prognosis, and disease stage is important for determining therapy. These findings offer the potential for further development of therapeutic regimens. Endoscopic esophageal ultrasound is an accurate and reproducible staging tool. It allows the physician to determine clinical stage and modify treatment. T2 N0 M0 or lesser stage tumors have acceptable surgical cure rates, and patients should undergo immediate resection. Patients with more advanced T3 or N1 tumors have a potential for cure but do poorly with surgery alone. These patients should be considered for multimodality therapy. Palliative therapy should be given to patients with hematogenous metastatic disease. Treatment stratification by stage proves that esophageal carcinoma is not a uniformly fatal disease without hope for cure.     

Value of MRI, CT and findings in staging of gynecologic malignancies

PURPOSE: The present study was designed to compare the value of MRI, CT and clinical examination in local tumor staging of gynaecologic malignancies. PATIENTS AND METHODS: 99 patients with clinically suspected carcinoma of the cervix uteri, ovarian carcinoma or tumor recurrence after gynaecologic cancer underwent all three staging modalities. Furthermore CT and MRI were compared in detecting lymph node metastasis and peritoneal implants. RESULTS: MRI was superior to CT and clinical staging in local tumor staging with an accuracy of 77% for cervical carcinoma and of 88% for recurrent tumors, whereas CT achieved an accuracy of 65% and 55% and clinical staging 60% and 63% accuracy for carcinoma of the cervix and recurrent cancer. Especially for local staging of these two tumor entities MRI is very useful. MRI and CT reached comparable results in the detection of ovarian tumors with an accuracy of 73% for MRI and 69% for CI. Both imaging modalities also showed equal results in the detection of lymph node metastasis, so that primary the cost saving use of CT tumor staging for ovarian lesions and lymph node metastasis should be favoured.     

Transrectal ultrasonography and operative selection for early carcinoma of the rectum

BACKGROUND: Transrectal ultrasonography (TRUS) supplements clinical evaluation of early carcinoma of the rectum in selecting patients for local operative therapy, such as transanal excision (TAE). STUDY DESIGN: This study was done to evaluate the accuracy of ultrasonographic staging of tumor depth (T stage) in patients with suspected early carcinoma of the rectum, to compare ultrasonographic with clinical T-staging accuracies within this patient group, to determine if any specific tumor characteristics (configuration, size, location) predispose toward ultrasonographic T-staging inaccuracy, and to examine the role of TRUS in operative selection for patients with early carcinoma of the rectum. RESULTS: Between April 1990 and December 1992, 62 patients with primary carcinoma of the rectum underwent ultrasonographic staging (uT), whereby three uT4, 27 uT3, 24 uT2 and eight uT1 carcinomas were identified. Of the 32 patients with suspected intramural (uT1 or uT2) disease, 27 underwent prompt operative excision or resection at our institution, allowing comparative histopathologic staging. In this highly selected patient subset, uT1 staging was correct in all instances; uT2 staging was incorrect in 45 percent of instances, with 30 percent having unpredicted transmural penetration. Ultrasonographic and clinical staging accuracies were quantitatively similar, and no tumor characteristics were consistently associated with ultrasonographic imprecision. CONCLUSIONS: Among patients with clinically suspected early carcinoma of the rectum, the decision to perform TAE is supported by ultrasonographic T1 staging. By contrast, the decision to perform TAE cannot be based solely on ultrasonographic T2 staging, because of the possibility for transmural penetration of tumor.     

Endoscopic ultrasonography with the ultrasonic esophagoprobe

Forty-one patients with either stenosing esophageal and cardia carcinoma (n = 27) or suspected tumor stenosis (n = 14), in whom conventional endosonography had failed, were evaluated with the ultrasonic esophagoprobe (blind probe). The main indication was locoregional staging of esophageal and cardia carcinomas, or restaging after radiotherapy or combined chemotherapy and radiotherapy. In 37% of the patients (10 of 27) an EUS T4 carcinoma was diagnosed, and in 63% (17/27) an EUS-T3 one. Regional lymph-node metastases were diagnosed in 96% of the cases. EUS restaging after nonsurgical palliative treatment detected tumor lesions in three of eight patients. Despite the fact that the imaging quality is still not satisfactory, our results suggest that the limitations of endoscopic ultrasonography (EUS) examination due to stenosing tumor growth can be overcome by the use of this ultrasonic esophagoprobe or similar instruments. Further technical developments may improve the resolution as well as the imaging quality in the celiac axis region.     

Nuclear distribution of human DNA topoisomerase IIbeta: a nuclear targeting signal resides in the 116-residue C-terminal tail

Surgery is considered to be a standard therapy for stage III or the earlier stage of esophageal cancer. However, the standard therapy is changing because of the recent advances in the non-surgical approach, especially chemoradiotherapy. Various obstacles remain to estimate the outcomes of combined modality therapy, while the consensus of the treatment for such stage excluding T4 diseases are as follows: 1) Concurrent chemoradiotherapy has a superior outcome to radiation alone in patients with squamous cell carcinoma. 2) Recent chemoradiotherapy without surgery achieves results comparable to surgery alone. 3) Preoperative chemoradiotherapy can achieve better results than surgery alone in patients with adenocarcinoma. 4) Preoperative chemotherapy is still experimental. Our preliminary results of chemoradiotherapy for esophageal cancer also showed comparable data to extended surgery in terms of survival. Some significant points to be elucidated regarding combined modalities in stage III or earlier are: 1) the comparison of definitive chemoradiotherapy with Japanese extended surgery, and 2) evaluation of efficacy of surgery after chemoradiotherapy. However, these studies require randomized trials comparing surgery with non-surgical treatment, which appears to present significant obstacles. Critical estimation for each study should be recommended based on accurate clinical staging, biological behavior, and intention-to-treat.     

Squamous cell carcinoma of the thoracic esophagus following radiation therapy for breast cancer

Between 1981 and 1995, 4 patients (3 females, 1 male; aged 48-80) were diagnosed with squamous cell carcinoma of the esophagus, following mediastinal irradiation for breast cancer. The interval between irradiation and the presentation of esophageal cancer was 10.75 years on average (7-19). The treatment consisted of: radiotherapy only; a partial esophagectomy with proximal gastrectomy without post-operative radiotherapy; laser photocoagulation for a superficial tumor; and, palliative treatment including gastrostomy, tracheal photocoagulation and chemotherapy for 1 patient suffering from advanced stage cancer with tracheal invasion, respectively. Radiotherapy of the esophageal cancer (exclusive or adjuvant) should take into account previous esophageal radiation therapy. The indications of curative excision surgery are the same as for other types of esophageal cancer, but the anastomoses should be performed in a non-irradiated area. Excision by esophageal stripping without thoracotomy is contraindicated because of the presence of peri-esophageal sclerosis. Preventive measures in radiation therapy for breast cancer are suggested.     

Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers

The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.     

Cell cycle arrest and release in starfish oocytes and eggs

A neural net-based, semiautomated, interactive computerized cell analysis system (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells from 138 esophageal smears obtained by lavage, brushings, or balloon from as many patients. From each smear, trained human observers examined 128 cell images selected by the machine. Abnormal cells were identified in all 35 patients with cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears, the displayed images allowed the recognition of effects of radiotherapy and, in 14 smears, the diagnosis of a specific tumor type, such as squamous cell carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the diagnosis of "carcinoma, not further specified," was established. One case of esophageal carcinoma in situ, not previously recognized on a smear or in the biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the smear, were identified in PAPNET-generated images. The possible application of the apparatus to the triage of smears and population screening for esophageal and gastric carcinoma precursors is discussed.     

Expression of amphiregulin, a novel gene of the epidermal growth factor family, in human gastric carcinomas

The expression of mRNA for amphiregulin (AR), a novel gene of the epidermal growth factor family, was examined in 8 human gastric carcinoma cell lines and 32 gastric carcinoma tissues as well as corresponding normal mucosa. Of the 8 gastric carcinoma cell lines, 7 expressed 1.4 kb AR mRNA at various levels. The expression of AR mRNA by TMK-1 and MKN-28 cells was increased by treatment with epidermal growth factor or transforming growth factor a. In surgical cases, all the gastric carcinoma tissues and their adjacent normal mucosa expressed AR mRNA. Interestingly, 20 (62.5%) out of 32 tumors expressed AR mRNA at higher levels than their corresponding normal mucosas (tumor/normal > or = 1.2). No obvious correlation was observed between the AR mRNA levels and the histological types or tumor staging of gastric carcinoma. Immunohistochemically, AR protein was localized to the cytoplasm and/or nucleus in tumor cells. These results suggest that AR produced by tumor cells may be involved in the pathogenesis and/or progression of human gastric carcinoma.     

Local staging with CT of tumors of the upper urothelium

OBJECTIVE: To evaluate the ability of computerized tomography (CT) to stage transitional cell carcinoma of the upper urinary tract. METHODS: 29 transitional cell carcinoma of the upper urinary tract submitted to nephroureterectomy were retrospectively evaluated. All 29 tumors had preoperative CT scans performed to stage the lesion. The pathological staging was compared to that of CT. RESULTS: 10 of the 29 tumors had CT evidence of tumor extension and 19 had localized noninvasive tumor on CT. Of the 10 patients with CT findings of tumor extension, 2 (20%) had superficial tumors and 8 (80%) had tumors that invaded into the adventitial fat, renal parenchyma or perirenal fat (pT3, pT4). Of the 19 patients with localized noninvasive tumor on CT, 13 (68%) had superficial tumors and 6 (32%) had pT3 or pT4 tumors. CT sensitivity for tumor invasion was 57% with a specificity of 87.5%. CONCLUSIONS: Our analysis shows that CT is of limited value in staging these tumors. When CT demonstrates direct tumor extension through the renal pelvic or ureteral wall, it is a sensitive indicator of high-stage tumor. However, the results obtained in low stage tumors must be viewed with caution.     

Thymic carcinoma. Five distinctive histological variants

Five histologically distinct variants of thymic carcinoma are described: mixed small cell undifferentiated squamous cell carcinoma (three cases), basaloid carcinoma (two cases), mucoepidermoid carcinoma (one case), clear cell carcinoma (one case), and sarcomatoid carcinoma (one case). While forming a heterogeneous group, these tumors bear the common features of an anterior mediastinal location and lack of evidence of a primary tumor elsewhere, marking them as primary thymic neoplasms. All except the sarcomatoid variant are morphologically related to similar malignant neoplasms of other organs. These tumors should be recognized as morphological variants of primary thymic carcinoma and demonstrate the ability of thymic epithelium to differentiate toward a variety of different cell types.     

Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma: frequency, associated tumor characteristics, and impact on prognosis

BACKGROUND: The purpose of this study was to investigate micrometastasis (MM) and tumor cell microinvolvement (TCM) in the regional lymph nodes of patients with esophageal squamous cell carcinoma (SCC). METHODS: MM was defined as individual tumor cells or tumor cell clusters <0.5 mm in greatest dimension with a surrounding stromal reaction. TCM was defined as individual tumor cells or tumor cell clusters without a surrounding stromal reaction. One thousand nine hundred and fifty-four lymph nodes were dissected from 69 complete (R0) resection specimens of TNM classified pT1-3, pN0 or pN1, and M0 esophageal SCC. These lymph nodes were examined immunohistochemically using the monoclonal antibody cocktail AE1/AE3 for cytokeratins. The primary tumors were immunostained with an anti-E-cadherin monoclonal antibody. RESULTS: MM +/- TCM was found in 13 cases (31.7%) and TCM alone in 2 cases (4.9%) of the 41 pN0 cases. The pN0 patients with MM (but not TCM) had the same shorter survival as the original pN1 cases (P < 0.05). Of the 69 primary tumors, 49 (71.0%) had reduced or negative E-cadherin expression that showed a correlation with the occurrence of lymph node metastases (original pN1), MM, and TCM, but not prognosis. CONCLUSIONS: The results of the current study show that, in SCC of the esophagus, MM, but not TCM, in the regional lymph nodes is prognostically equivalent to metastasis and should be examined by immunohistochemistry to classify these cases correctly as pN1.     

Diet supplemented with yoghurt or milk fermented by Lactobacillus casei DN-114 001 stimulates growth and brush-border enzyme activities in mouse small intestine

Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with carcinoma of the upper gastrointestinal tract. A series of randomized prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in gastric or esophageal cancer. The available data on the role of neoadjuvant preoperative therapy in these patients as yet permit no conclusion. While neoadjuvant therapy may reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that, compared to primary resection, a multimodal approach does not result in a survival benefit in patients with loco-regional, i.e. potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e. tumors for which complete removal with primary surgery appears unlikely, neoadjuvant therapy increases the chance for complete tumor resection on subsequent surgery. However, only patients with objective histopathologic response to preoperative therapy appear to benefit from this approach. Compared to preoperative chemotherapy alone, combined radio-chemotherapy increases the rate of response, particularly in squamous cell esophageal cancer, but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently only be performed in experienced centers within the context of prospective clinical trials. The identification of factors that would allow prediction of response to neoadjuvant or adjuvant therapy is the focus of ongoing studies.     

Endometrial cancer

Carcinoma of the uterine corpus (endometrial cancer) remains the gynecologic malignant disease with the highest annual prevalence in the United States. The most common histologic type is adenocarcinoma, although more aggressive variants (e.g., papillary serous carcinoma and clear cell carcinoma) have been identified. Risk factors that are strongly associated with the development of endometrial cancer include tamoxifen therapy, obesity, and stimulation from unopposed estrogen (from exogenous sources or endogenously secreting ovarian tumors). The current staging system of the International Federation of Gynecology and Obstetrics is based on surgical-pathologic findings. Survival has been directly correlated with tumor stage in this staging system. The cornerstone of therapy is total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pelvic and para-aortic lymphadenectomy may provide additional prognostic information but probably does not confer a therapeutic advantage. Moreover, such nodal dissections predispose to the development of complications, especially in women who subsequently receive pelvic irradiation. Other than surgical treatment, irradiation is the single most active therapy for endometrial carcinoma. In fact, some women who are not candidates for hysterectomy because of medical contra-indications can be cured with radiation alone. Adjuvant therapy following hysterectomy is based on patient- and tumor-related features that provided prognostic information for incidence and pattern of recurrence. Adjuvant treatment usually includes pelvic irradiation for selected patients. Current investigational strategies are directed at the role of whole-abdomen irradiation, extended-field irradiation, and systemic chemotherapy. The most active systemic agents include cisplatin, doxorubicin, paclitaxel, and progestins.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Human genes for KNSL4 and MAZ are located close to one another on chromosome 16p11.2

CD31 is a specific and sensitive marker of endothelial differentiation. Previous reports have described its immunoreactivity in large series of soft tissue neoplasms, as well as its comparison with other available and commonly used endothelial markers. CD31 reactivity in carcinomas or mesotheliomas has been incompletely addressed, however. Hence, we applied anti-CD31 (JC70/A, DAKO, Carpinteria, Calif) to 290 previously characterized neoplasms by using a modified avidin-biotin-peroxidase complex technique following microwave epitope retrieval. Seven carcinomas showed plasmalemmal-based immunoreactivity (2 papillary thyroid carcinomas, 2 mucoepidermoid salivary gland carcinomas, 1 cutaneous adnexal tumor, 1 cutaneous squamous cell carcinoma, and 1 esophageal squamous cell carcinoma); the remaining 283 lesions were negative for this marker. We conclude that anti-CD31 immunostaining in carcinomas and mesotheliomas is rare. These findings support the concept that CD31 is a reliable marker of endothelial differentiation and should be included in diagnostic immunohistochemical panels when vascular tumors enter the differential diagnosis.     

PET evaluation of therapeutic limb perfusion in Merkel's cell carcinoma

An 87-yr-old woman diagnosed with recurrent Merkel's cell carcinoma was treated with therapeutic limb perfusion and underwent PET scanning with 18F-fluorodeoxyglucose (FDG). PET studies were obtained before and after treatment to determine the response to the intervention. A baseline whole-body study was obtained to assess the extent and degree of disease activity. This was followed by a repeat PET scan 2 mo. later after treatment with isolated limb chemotherapy with high-dose melphalan and tumor necrosis factor-alpha. The initial scan demonstrated multiple foci of high FDG uptake in the left calf, a left supraclavicular lesion and also detected concurrent keratinizing squamous cell metastasis in the right axilla. A repeat PET study showed complete metabolic resolution of the lesions in the left calf after treatment. FDG PET may be a useful technique for staging Merkel cell carcinoma and for assessing the tumor response after therapy of this rare tumor.     

Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin-dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma

We previously reported frequent loss of heterozygosity on chromosome 9p in esophageal carcinomas and suggested that a tumor suppressor gene located on this chromosomal arm might be involved in development of these cancers. Since recently published studies have shown that a gene mapped on chromosome 9p21, MTS1/CDK4I (multiple tumor suppressor 1/cyclin-dependent kinase 4 inhibitor), is frequently mutated in various types of tumors, we chose to examine esophageal squamous cell carcinomas for mutations in this candidate gene. DNA sequence analyses revealed somatic mutations of MTS1/CDK4I in 14 of 27 tumors examined; 8 were frame-shift mutations and 6 were missense mutations. These results suggested that the MTS1/CDK4I gene is a tumor suppressor the inactivation of which plays an important role during carcinogenesis of the squamous cell type of esophageal carcinoma.