Ductal Infiltration Research Articles

Abstract GS2-01: The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ

Abstract Background: With the implementation of widespread breast cancer screening, the diagnosis of Ductal Carcinoma In Situ (DCIS) has increased 5 fold. Most cases are treated with combinations of surgery, radiation and endocrine therapy, reducing the risk of second events, including ipsilateral invasive cancer. Without standard markers to confidently identify the most indolent lesions, a subset of cases are likely over-treated. The mutational landscapes of DCIS and invasive ductal carcinoma (IDC) are similar and not sufficient to identify higher risk lesions with recent studies suggesting that clonal selection plays a limited role in progression. Histological analysis highlighted the role of the extracellular matrix and immune-surveillance to maintain duct integrity and limit progression. Due to the small size, limited availability and quality of research specimens, few biomarker studies investigated pure DCIS with adequate follow-up or genome-wide methods, let alone integrated more than one type of biomarker. Unlike breast cancer, there is no comprehensive, systematic, multi-modal atlas of DCIS, limiting the ability to test broad and novel hypotheses and characterize processes maintaining breast tissue homeostasis. Methods: Through sequential sectioning of pure DCIS archived specimens, a total of 70 histological regions from 40 cases were annotated and profiled using up to 3 platforms: multiplex immuno-histochemistry (mIHC), RNA-seq, and whole-exome sequencing. Stromal and epithelial spatial distribution of immune cells and states were quantified using mIHC. The epithelial compartments were microdissected and profiled using genome-wide gene expression, DNA mutations and copy number alterations. Results: Epithelial regions were classified according to expression subtypes consistent with histological markers, highlighting associations with the lesion architecture and grade. Compared to solid pattern, cribriform pattern DCIS has induced EMT processes and repressed proliferation processes, a trend reminiscent of low-recurrence-risk expression signatures measured in IDC. The DNA copy number burden increased with grade and the mutational burden was the highest in solid DCIS. Both were higher in Her2+ cases. The clustering of mutations at chromosome 17p - attributed to the APOBEC-driven Kataegis phenomenon - was observed in a subset of regions, suggesting this event can occur in pre-invasive lesions. All DCIS had somatic alterations of at least one known driver gene with some associated with grade (TP53) or expression subtype (ERBB2). Multi-region profiling available in a subset of samples revealed genetic heterogeneity of likely-driver events between proximal regions of similar histological characteristics. The density and proliferative states of selected immune cells - including T-cells, B-cells and Macrophages - highlights the diversity of the tumor immune environment with the highest densities observed in Her2+ ducts and stroma, minimal ductal infiltration in other lesions, fewer dividing B- and T-cells around the more proliferative areas and a small number of regions depleted from any adaptive immune cells. Conclusion: This first multi-modal profiling of pure DCIS reveals an unsuspected diversity of molecular and microenvironmental states and presents their association with progression risk factors. The observations support the need for stronger integration of molecular and clinicopathology features, especially at sub-histological levels, to ensure the findings can be interpreted in the correct clinical and phenotypic context. The compatibility of the approach with archived specimens supports the expansion to larger retrospective DCIS collections with outcomes. Citation Format: Olivier Harismendy, Daniela Nachmanson, Mark F. Evans, Hidetoshi Mori, Adam Officer, Christina Yau, Joseph Steward, Huazhen Yao, Thomas O'Keefe, Farnaz Hasteh, Gary S. Stein, Kristen Jepsen, Michael Campbell, Donald L. Weaver, Gillian L. Hirst, Brian L. Sprague, Laura J. Esserman, Jonathan A. Gordon, Alexander Borowsky, Janet L. Stein. The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-01.

Predictive prognostic value of BRCA1 screened by whole genome expression profiling in ductal carcinoma in situ

Objective To investigate the role of the predictive prognostic value of BRCA1 screened by whole genome expression profiling in ductal carcinoma in situ. Methods Collected 4 cases of breast ductal carcinoma and 4 cases of breast invasive ductal carcinoma fresh samples from January 2014 to June 2014, and the difference of BRCA1 expression on whole genome expression profiling was analyzed by microarray comparative genomic hybridization. The expression of BRCA1 was detected by immunohistochemistry in 70 cases of ductal carcinoma in situ of the breast, and the prognosis of intraductal carcinoma was evaluated. Results BRCA1 gene differentially expressed in invasive ductal carcinoma and ductal carcinoma in situ by screening. The positive rate of BRCA1 protein in breast ductal carcinoma in 14.3%(10/70), its expression had no significant relationship with age (P=0.959), menopause (P=0.959), tumor size (P=0.627), axillary lymph node status (P=1.000), HR status (P=0.958), HER-2 status (P=1.000), P53 expression (P=0.460). ductal carcinoma with micro-infiltration ratio in BRCA1 negative group was higher than BRCA1-positive group (P=0.043). The median follow-up of 47 months, Disease-free survival rate of all was 97.1%. Disease-free survival of BRCA1 negative group and BRCA1-positive group had no significant difference (96.7% vs 100%, P=0.569), over all survival of BRCA1 negative and positive groups was 100%. Conclusions BRCA1 expression may not predict the prognosis of intraductal carcinoma, but ductal carcinoma in situ with microinvasion group ratio in BRCA1 negative was higher than ductal carcinoma in situ group, BRCA1 may take affect within ductal carcinoma infiltration process work. Key words: Ductal carcinoma in situ; Gene expression profiling; Comparative Genomic Hybridization; BRCA1 protein; Prognosis

Pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors is an Independent Poor Prognostic Factor.

The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs. The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection. MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P<0.001), with a 5years recurrence-free rate of 41%. On multivariate analysis, MPD involvement was significantly associated with nodal metastasis [odds ratio (OR) 16; 95% confidence interval (CI) 3.8-89; P<0.001] and recurrence (OR 8.0; 95% CI 1.7-46; P=0.009). The radiology-pathology correlation revealed that stenosis of the MPD was due to periductal and/or intraductal tumor invasion. Cases with MPD involvement had microscopic venous invasion (P=0.010) and perineural infiltration (P=0.002) more frequently than did those with no ductal infiltration. MPD involvement in PNETs may serve as an imaging sign indicating an aggressive clinical course.

Diagnostic accuracy of metastatic axillary lymph nodes in breast MRI.

PurposeThe most important prognostic variable for early stage breast cancer is the status of axillary lymph nodes. The aim of this study was to evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) for metastatic axillary lymph node in breast cancer cases with post-operative sentinel lymph node biopsy (SLNB) results.Materials and methodsWomen aged between 21 and 73 years who were diagnosed with malignant mass lesion of the breast between 2013 and 2015 were included in this study. The preoperative MR images of patients with diagnosis of breast cancer was evaluated to determine axillary lymph node status. Axillary lymph node size, long axis to short axis ratio, lymph node contours, cortical thickness to anteroposterior diameter ratio, the presence of a fatty hilum and contrast enhancement patterns (homogenous or heterogenous) was noted. Additionally, the presence of comet tail sign which a tail extending from an enhancing breast lesion into the parenchyma and might represent ductal infiltration on post-contrast series was also noted. All data obtained from this evaluation was compared with postoperative SLNB results.ResultsMetastatic nodes were found to have a longer short axis when compared to reactive nodes (p = 0.042; p < 0.05). The long axis to short axis ratio was notably lower in metastatic nodes when compared to reactive nodes. Cortical thickness was higher in metastatic nodes when compared to reactive nodes (p = 0.024; p < 0.05). Comet sign was observed in 15 of metastatic nodes (73.3 %) and in one (5 %) reactive node. This difference was statistically significant (p = 0.001; p < 0.01). While fatty hilum was seen in 40 % of metastatic nodes (n = 6), it was seen in all (n = 20) reactive nodes. This difference was statistically significant (p = 0.001; p < 0.01).ConclusionsMRI is a non invasive sensitive and specific imaging modality for evaluating the axilla. We have shown that with the help of comet tail sign and status of fatty hilum contrast enhanced MRI has the highest sensitivity of 84.7 % for detecting axillary lymph node metastases (Singletary et al. in Semin Surg Oncol 21(1):53–59, 2003).

Abstract P4-04-07: Breast cancer tissue context determines whether inflammation with bacterial/psoriasin signature is pro- or anti-carcinogenesis

Abstract Objective: It is often neglected that breast tissue microbiota and systematic bacterial infection actively and potently influence the development of breast cancer. With reports of both pro-cancer and anti-cancer roles of bacterial inflammation, the actual effect of bacterial inflammation to breast cancer and its mechanism remain unclear and are of our interests. Rationale: Different from other human tissues, breast tissue microbiota is majorly Gram-negative at both normal and pathological statuses. We discovered that bacterial inflammation in breast tissue has a signature of Psoriasin (S100A7) impact which resembles psoriasis of the skin. However, this Psoriasin mediated inflammation can either promote or inhibit breast cancer development. We hypothesize that different tissue context determines the differential effects of bacterial/Psoriasin inflammation on breast cancer development. Results: We first verified the presence of commensal Gram-negative microbiota (and LPS) in breast tissues under normal and pathological circumstances using mouse models. We observed that in both normal and cancerous breast tissues, bacterial factors (such as LPS) found in breast triggered secretion of Psoriasin by mammary adenocytes and Psoriasin mediated inflammation. This type of inflammation is featured by macrophage recruitment and ductal infiltration induced by Psoriasin. However, in normal tissues, macrophages matured into M1 type (iNOS positive); whereas in cancerous tissues, macrophages matured into M2 type (Arginase-1 positive). In normal tissues, Psoriasin and M1 caused an unresolved accumulation of inflammation in mammary ducts without lactation, which might lead to accelerated cancer initiation. In tumors, Psoriasin and M2 increased tumor growth and metastasis in immune-competent mammary epithelial specific expression mouse models. This was further confirmed in human patient samples and large cohort bioinformatic analysis. Using human breast cancer cell lines and nude mice, we elucidated that inflammation related Psoriasin upregulation and secretion in cancer cells had differential effects on tumor growth depending on its tissue source. Psoriasin increased cell proliferation and tumor growth in basal-like cancer cells; whereas it decreased cell proliferation and tumor growth in non-basal-like cancer cells. And this difference was mediated through differential regulation of the NF-κB/miR-29b/p53 pathway. in vitro molecular study and in vivo models verified the important role of miR-29b switch in the differential effects of Psoriasin in different tissue types of breast cancer cells. Conclusion: Bacterial/Psoriasin inflammation differentially influences breast cancer development depending on the tissue context, and it involves the effects on macrophages and cancer cells. Our work provides novel potentials to improving prognosis and targeting inflammation to treat breast cancer in personalized medicine. Citation Format: Helong Zhao, Mohd W Nasser, Tasha Wilkie, Ramesh K Ganju. Breast cancer tissue context determines whether inflammation with bacterial/psoriasin signature is pro- or anti-carcinogenesis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-07.

Development of an Animal Model of Fibrous Cholangitis in Pigs

ABSTRACTIntroduction: The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Material and Methods: Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0–5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Results: Statistically significant differences were observed for most of the histopathological markers between the group of pigs’ offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Conclusions: Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

ENDOSCOPIC DIAGNOSIS AND TREATMENT OF AMPULLARY NEOPLASM (WITH VIDEO)

For ampullary cancer, pancreaticoduodenectomy is considered to be the standard treatment. Endoscopic papillectomy (EP) has been utilized in cases of ampullary adenoma since the early 1980s. We aimed to provide a review concerning EP. We conducted a review of studies regarding EP for ampullary neoplasms. Since neither lymphatic permeation, vascular invasion, nor lymph node metastasis is observed in patients with ampullary cancer limited to the mucosa, EP of such tumors without ductal infiltration into the pancreatic/bile duct can be justified as radical treatment. For its application in patients with ampullary neoplasms, accurate pretreatment staging is indispensable. EUS, which can be carried out on an outpatient basis with a low risk of complications, is useful for differential diagnosis as well as detection of periampullary tumors. Although intraductal US of the bile duct tends to result in overestimation of tumor staging in cases of ampullary neoplasm, it can provide useful information for making therapeutic decisions, especially in cases appropriate for EP. While the technical success rate of EP is high, the complication rate and recurrence rate are not as low as a satisfactory level. Pancreatic duct stenting after EP is expected to contribute to prevention of post-EP pancreatitis. There is no consensus regarding the mode of resection current nor the need for addition of biliary/pancreatic sphincterotomy and biliary stenting. EP has been reported to be useful in selected patients with ampullary neoplasms. Data on further long-term follow up after EP are awaited.

Initial clinical test of a breast‐PET scanner

The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques. The PEM/PET system consists of two pairs of rotating radiation detectors located beneath a patient table. The scanner has a spatial resolution of ∼2 mm in all three dimensions. The subjects consisted of five patients diagnosed with locally advanced breast cancer ranging in age from 40 to 55 years old scheduled for pre-treatment, conventional whole body PET imaging with F-18 Fluorodeoxyglucose (FDG). The primary lesions were at least 2 cm in diameter. The images from the PEM/PET system demonstrated that this system is capable of identifying some lesions not visible in standard mammograms. Furthermore, while the relatively large lesions imaged in this study where all visualised by a standard whole body PET/CT scanner, some of the morphology of the tumours (ductal infiltration, for example) was better defined with the PEM/PET system. Significantly, these images were obtained immediately following a standard whole body PET scan. The initial testing of the new PEM/PET system demonstrated that the new system is capable of producing good quality breast-PET images compared standard methods.

Diagnosis of Ampullary Cancer

Endoscopic papillectomy has been reported to be the treatment of choice in patients with ampullary adenoma. For ampullary cancer, pancreaticoduodenectomy is the standard treatment. Since neither lymphatic permeation, vascular invasion, nor lymph node metastasis is observed in patients with ampullary cancer limited to the mucosa, endoscopic resection of such tumors can be justified if no ductal infiltration into the bile or pancreatic duct is documented. For its application, accurate preoperative staging is mandatory. Transpapillary intraductal ultrasonography can provide useful information for making therapeutic decisions, especially in the selection of patients for endoscopic papillectomy.

Surgical Management of Infrahilar/Suprapancreatic Cholangiocarcinoma: an Analysis of the Surgical Procedures, Surgical Margins, and Survivals of 77 Patients

BackgroundOptical surgical management of infrahilar/suprapancreatic cholangiocarcinoma remains controversial. MethodsBetween 1988 and 2006, 77 patients with infrahilar/suprapancreatic cholangiocarcinoma underwent curative surgical resections following our intention-to-treat strategy. The clinicopathological factors affecting survival were evaluated using univariate and multivariate analyses with regard to the surgical procedures and surgical margins. ResultsThe surgical procedure included extrahepatic bile duct resection alone (EHBD; n = 17), major hepatectomy combined with extrahepatic bile duct resection (MHx; n = 26), pancreaticoduodenectomy (PD; n = 28), and MHx and concomitant PD (HPD; n = 6). Performance of MHx and/or PD in addition to EHBD increased surgical morbidity (p = 0.001). Among patients undergoing the four surgical procedures (EHBD, MHx, PD, and HPD), no significant difference was found in the incidence of positive overall surgical margins (53%, 65%, 46%, and 67%, p = 0.51) or long-term survivals (median survival time, 51, 27, 41, and 22 months, p = 0.60). A multivariate analysis revealed that perineural invasion (95% confidence interval, 1.1–12.3, p = 0.009), nodal metastasis (1.6–6.8, p = 0.001), and blood transfusion (1.1–3.9, p = 0.02) were independent predictors of a poor outcome. Perineural invasion was associated with positive radial margins (p = 0.045) and submucosal ductal infiltration (p = 0.03). ConclusionPerineural invasion, rather than the type of surgical procedure, had a significant impact on surgical curability and survival of patients with infrahilar/suprapancreatic cholangiocarcinoma treated according to our intention-to-treat strategy.

Factors influencing false negative diagnosis of 3D-MRI in pre-operative breast cancer patients.

Abstract Abstract #4005 Introduction: We presented 3D-MRI will be the useful breast imaging tool in diagnosing intraductal spread and tumor size in breast cancer patients (ASCO 2008). But, false negative cases were very important in breast conserving surgery and careful management was needed in 3D-MRI guided surgery. This study was to review imaging diagnosis using 3D-MRI and to evaluate factors influencing false negative diagnosis of 3D-MRI, retrospectively. Material and methods: From July 2000, pre-operative 3D-MRI was underwent 433 cases of breast cancer patients. Images were obtained 426 cases (98%). Tumor size between 3D-MRI and resected specimens were evaluated retrospectively. Cases with tumor size difference between 3D-MRI and resected specimens less than 1cm were defined related cases and cases with tumor size in 3D-MRI was 1cm more smaller than resected specimens were defined false negative cases. Investigated factors influencing false negative diagnosis of 3D-MRI were age, patterns of 3D-MRI images, presence of pre-operative chemotherapy, histological type, histological grade, microscopical invasive tumor size (mm) and presence of ductal spreading. From April 2005, the entire specimen was serially step cut and evaluated. Results: Tumor diameter from nipple side to lateral margin were measured by MRI and specimens, tumor size was correlated between MRI and specimens, significantly (n=118, r=07186, P &amp;lt; 0.001). On Multivariate analysis revealed that factors influencing 3D-MRI diagnosis were presence of ductal spreading (p=0.0002), patterns of 3D-MRI images (p=0.06) and presence of pre-operative chemotherapy (P=0.04). Factors influencing false negative diagnosis of 3D-MRI were presence of pre-operative chemotherapy (P&amp;lt;0.05), presence of ductal spreading (P&amp;lt;0.01) and infiltration of lymphocyte in the edge of ductal spreading (P&amp;lt;0.05). Selection for breast conserving surgery and margin width were based by 3D-MRI images. The proportion of breast-conserved surgery were obtained 89% (380/426 cases) and local failure seen only 6 cases (local failure rate 1.4%) in 3D-MRI guided surgery. (6-94 months, median follow up 51 months).&amp;#x2028; Conclusion: These results suggest that MRI will be the useful breast imaging tool in diagnosing intraductal spread and tumor size in breast cancer patients. But, caution will be needed in cases with pre-operative systemic therapy and cases expected ductal spreading by other imaging tools. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4005.

Klatskin-like Biliary Sarcoidosis

Purpose: Clinical Vignette: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that presents most often in young adults with hilar adenopathy, pulmonary infiltrates, skin or eye lesions. Hepatobiliary involvement is asymptomatic in most, with non-caseating granulomas seen often. Cholestatic hepatitis with liver chemistry resembling PBC or PSC has been described. Intra-hepatic cholestasis, hepatosplenomegaly, pre-sinusoidal portal hypertension, portal fibrosis, and cirrhosis may be seen. Abnormalities of the large bile ducts and extra-hepatic tree is rarely seen, and we describe a Klatskin-like biliary confluence granulomatous obstruction that responded to balloon dilation, stenting, and corticosteroid therapy. Case: A 38 yr. old caucasian female presented with painless jaundice. She complained of pruritus, weakness, fatigue, dark urine and malaise. Initial labs: Bilirubin 11, AST-107, ALT-92, GGT-431 (Nl 15–85), Alk. Phos-635, CEA-1.2, Nl p-ANCA, Nl Ig's, ACE-28 (Nl 8–21); ANA, AMA, copper, Ferritin were WNL. U.S. revealed intra-hepatic duct dilations; CT and MRCP with confluence region mass effect with marked proximal ductal dilation. A 3 cm portacaval node was noted; ERCP with Spyglass cholangioscopy displayed a tight confluence stricture, with extension into the right hepatic system; After balloon dilation of both right and left ducts, cholangioscopy revealed a nodular duct wall and brushings and directed biopsy bites were collected. Histology from the confluence revealed non-caseating granulomas with chronic cholangitis; No malignancy was detected. A 10 F stent was placed into the dominant right system and the bilirubin fell from 17 to 11 mg/dl overnite. The pateint was treated with Urso and 40 mg of Prednisone. Follow-up 2 weeks later: Bili.-1.5, GGT-135, ALT-48. Conclusions: Sarcoidosis is a chronic granulomatous disease that may present in young adults as a hepatocellular or cholestatic process. Extra-hepatic biliary obstruction may result from peri-ductal adenopathy or from ductal infiltration. Cholangioscopy may prove beneficial in directing biopsies and/or brushings to rule out carcinoma. Biliary sarcoidosis appears to be exquisitely sensitive to biliary stent decompression and corticosteroids.

Preoperative evaluation of ampullary neoplasm with EUS and transpapillary intraductal US: a prospective and histopathologically controlled study

Endoscopic papillectomy is performed in selected patients with ampullary neoplasm, and, thus, accurate preoperative tumor staging is indispensable for its application. Prospective and histopathologically controlled study. Single center. EUS and transpapillary intraductal US (IDUS) were performed in 40 patients with ampullary neoplasm before surgery (n = 30) or endoscopic papillectomy (n = 10). Ductal infiltration by a tumor into the bile duct (BD) or the pancreatic duct (PD) was also evaluated. The indication for endoscopic papillectomy was determined by findings obtained by EUS and IDUS. These findings were compared with histologic features of the resected specimens. Thirty-three patients had adenocarcinoma (14 pT1, 11 pT2, 8 pT3-4) and 7 had adenoma. Tumor depiction by EUS and IDUS was achieved in 95% and 100% of the patients, respectively. The diagnostic accuracy of EUS and IDUS in T staging was 62% and 86% in adenoma and pT1, 45% and 64% in pT2, and 88% and 75% in pT3-4, respectively. The overall accuracy by EUS and IDUS in T staging was 63% and 78%, respectively (P = .14). In 10 patients who underwent endoscopic papillectomy, the accuracy of IDUS in T staging with EUS and IDUS was 80% and 100%, respectively. Ductal infiltration into the BD and the PD was correctly assessed in 88% and 90% by EUS and in both BD and the PD in 90% by IDUS, respectively. Ductal infiltration was correctly diagnosed by EUS and IDUS in all patients who had a papillectomy. Although IDUS had a tendency of overestimation in tumor staging for ampullary neoplasm, it can provide useful information for making therapeutic decisions, especially in cases appropriate for endoscopic papillectomy.

Modes of spread in early ampullary cancer in terms of establishing proper indications for endoscopic papillectomy

Background: Endoscopic papillectomy for adenomas of the ampulla of Vater has been reported and is gaining acceptance as an alternative to surgery in the treatment of early ampullary cancer. However, whether endoscopic treatment is justified as a treatment of choice for early ampullary cancer remains controversial. The aim of the present study was to elucidate the possibility of endoscopic papillectomy as a treatment of early ampullary cancer from the review of pathology of cases treated by surgical resection.Patients and methods: Twenty‐three cases of early ampullary cancer (m—tumor limited to the mucosa of the ampulla 14; od—tumor that invades Oddi's sphincter, 9) treated by surgical resection from January 1984 to March 2003 were investigated as to the following: (i) macroscopic type, maximum size, and histological type of tumor; (ii) main location and extension of tumor; (iii) prevalence of extension into the lower bile duct or pancreatic duct, and relationship between ductal infiltration and macroscopic type, maximum size, main location, or depth of invasion of tumor; (iv) lymphatic permeation, vascular invasion, and lymph node metastasis; and (v) prognosis.Results: All cases were classified macroscopically as exposed‐tumor type or non‐exposed‐tumor type without ulceration. Extension into the lower bile duct or the pancreatic duct was observed in 43% of the cases. There was no correlation between ductal infiltration and macroscopic type, maximum tumor size, main tumor location, or tumor depth. No lymphatic permeation, vascular invasion, or lymph node metastasis were proven in cases with ampullary cancer confined to the mucosa. In the nine cases with involvement of Oddi's sphincter, lymphatic permeation and lymph node metastasis were observed in two cases and one case, respectively.Conclusion: Endoscopic treatment for early ampullary cancer confined to the mucosa without spread to the bile duct or pancreatic duct is justified as a treatment of choice if detailed histological examination of the resected specimen indicated no invasion beyond its margin.

Rationale for endoscopic management of adenoma of the papilla of Vater: options and limitations.

Several studies and our own results prove that endoscopic therapy in selected cases of benign adenomas is safe and technically feasible. In patients refusing surgery or patients with high comorbidity and poor physical health status, endoscopic resection is an excellent alternative. The decision for endoscopic or surgical excision of adenomas is determined by general health status, histology, size, location, and depth of the lesion. In carcinoma of the papilla of Vater it is important to assess the tumoral ductal infiltration correctly to determine whether endoscopic resection is a viable option. Intraductal ultrasound is essential before initiating treatment and it therefore contributes to conservative therapy in patients with tumors of the papilla of Vater. Temporary placement of a short pancreatic duct stent may protect against pancreatitis and might allow more excessive ablation of adenomatous tissue, especially around the pancreatic duct orifice. After endoscopic sphincterotomy, biliary and pancreatic endoprostheses can be inserted easily in cases of obstructed pathways or cholangitis and pancreatitis due to tumor obstruction. Argon plasma coagulation can be used to treat oozing tumor hemorrhages or to vaporize tumoral residues after endoscopic snare resection. Endoscopic surveillance is essential after surgical or endoscopic resection of adenomas of the papilla of Vater.

Adhesion of 8701-BC breast cancer cells to type V collagen and 67 kDa receptor.

Ductal infiltration carcinomas (d.i.c.) of the breast are potentially highly metastatic tumours, associated with drastic alterations of the architecture and molecular composition of the extracellular matrix at the tumour-host interface. 8701-BC, a recently characterized cell line, isolated from primary d.i.c., was used to study different aspects of tumor cell-substratum interactions. Since type V collagen deposition is augmented in d.i.c. we have examined the ability of 8701-BC cells to interact with this collagen species. We have found that cell binding to type V collagen was mediated by protein homologous to the 67 kDa laminin receptor (67-R). This conclusion is substantiated by the following observations: (a) a major band having an apparent molecular mass of 67 kDa and immunoreactive to the anti-67 R antibody was detectable by SDS-PAGE of the membrane proteins; (b) the antibody inhibited cellular adhesion to type V collagen in a dose-dependent way; (c) membrane proteins purified by affinity chromatography on type V collagen were immunoreactive to anti-67 R antibody, but not to anti-VLA1, VLA2 and VLA3 integrin antibodies. This receptor appears to have prominent carbohydrate-binding properties, since lactose competes with cell adhesion to type V collagen.

Left ventricular dysfunction following ligation of the ductus arteriosus in the preterm baboon

We evaluated the effect of early closure of the patent ductus arteriosus (PDA) on cardiac performance in a preterm baboon model of hyaline membrane disease. Eleven baboon fetuses were delivered at 75% gestation, resuscitated, and treated with conventional ventilation. The animals were divided into two groups, and underwent left thoracotomy at 2 hr of age. Group 1 ( N = 5) had ductal infiltration with formalin to maintain ductal patency. Group 2 ( N = 6) had ductal ligation. Hemodynamic parameters were compared between groups before and after surgical intervention. Examination of cardiovascular function was performed at intervals over a 24hr period using two-dimensional, M-mode, and pulsed Doppler echocardiography. Ventricular performance was significantly worse in the ligation animals as demonstrated by reduced left and right ventricular outputs and reduced left ventricular shortening. However, pulmonary disease and arterial blood gases were not different. Early ligation was also associated with significantly increased systemic vascular resistance. We conclude that early ductal ligation leads to impaired ventricular performance in the premature primate. We hypothesize that the PDA may protect the immature ventricle by preventing pressure overload during adaptation to postnatal life.

Steroid receptors in ductal infiltration carcinoma of the breast: Relationship with productive fibrosis and axillary node metastases

Steroid receptors in ductal infiltration carcinoma of the breast: Relationship with productive fibrosis and axillary node metastases

Combined prostaglandin therapy and ductal formalin infiltration in neonatal pulmonary oligemia

Prostaglandins and ductal formalin infiltration, singly and together, have been used in efforts to improve pulmonary flow in very ill newborn infants with right ventricular outflow tract obstruction. To evaluate the efficacy of concurrent use of prostaglandins and ductal formalin infiltration, we have reviewed our experience with 25 infants with right ventricular outflow tract obstruction and prostaglandin-ductal formalin infiltration therapy. Prostaglandin therapy was begun 22 +/- 21 hours (range 20 to 93 hours) before and was continued 20 +/- 18 hours (range 0 to 62 hours) following ductal formalin infiltration; prostaglandin administration was initiated at a dose of 0.05 to 0.1 microgram/kg/min and tapered postoperatively. Clinical cyanosis was diminished in 20 of 25 infants (80%) postoperatively. Systemic arterial pH and oxygen saturation both improved following prostaglandin-ductal formalin infiltration therapy from 7.35 to 7.41 (p less than 0.001) and from 35.7 to 50.3 (p less than 0.001), respectively. Persistent ductal patency (mean 219 +/- 191 days) was observed in 17 survivors of the early postoperative period (more than 14 days). Two of five infants who died within 14 days of operation had a widely patent ductus with resultant progressive congestive heart failure. The other three infants died as a result of operative technical problems, dysrhythmias, and thrombotic ductal closure, respectively. No correlation was observed between duration of ductus patency and operatively determined size of ductus, total prostaglandin dose, or duration of prostaglandin infusion. Secondary operative intervention was delayed by 92 +/- 74 days with prostaglandin-ductal formalin infiltration therapy; thus prostaglandin-ductal formalin infiltration therapy may have a role in selected neonates with right ventricular outflow tract obstruction.

CT and ERCP for the combined study of biliary tract diseases

The value of combined CT and ERCP for examining the bile ducts was studied retrospectively. CT on its own led to a correct diagnosis in 59% of cases. CT was valuable for estimating the calibre of the bile ducts, for localising the level of obstruction, for demonstrating calcified biliary concrements, and for showing peribiliary tumours. ERCP yielded a correct diagnosis in 67% of cases. The value of ERCP lies in the demonstration of poorly calcified and small concrements, strictures, tumours with ductal infiltration, and for investigating the post-cholecystectomy syndrome. Combining these two types of examination increases diagnostic accuracy to 82%.