Lugol chromoendoscopy combined with brush cytology in patients at risk for esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Patients with achalasia or malignancies of the head and neck are at increased risk for esophageal squamous cell carcinoma. The discussion of a screening and surveillance program is controversial. The aim of the present study was to determine the diagnostic potential of Lugol chromoendoscopy combined with brush cytology to diagnose esophageal squamous cell carcinoma and high-grade dysplasia. Secondly, the benefit of additional biomarkers was investigated. PATIENTS AND METHODS: A total of 61 patients (21 patients with achalasia and 40 patients with malignancies of the head and neck) were included. Chromoendoscopy with 1.2% Lugol iodine solution with targeted biopsies and brush cytology processed by digital image cytometry (DICM) and fluorescence in situ hybridization (FISH) from unstained lesions (USLs) and stained mucosa were performed. RESULTS: Six of the 61 patients had USLs ≥2 cm. Four patients had high-grade dysplasia (HGD) or carcinoma in situ (CIS). One patient with HGD and one patient with CIS were detected only after Lugol chromoendoscopy. The sensitivity and specificity for detected HGD or CIS in USLs ≥2 cm were 100% and 96.5%. No dysplasia was found in USLs <2 cm. DNA ploidy by DNA cytometry and p53 loss of heterozygosity (LOH) by fluorescence in situ hybridization showed no additional impact on diagnostic accuracy. CONCLUSIONS: Lugol chromoendoscopy enhances the detection rate of high-risk lesions with dysplasia or carcinoma in situ in large unstained lesions. Biomarkers such as aneuploidy and p53 LOH from brush cytology were not of additional benefit in this setting.

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer.

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter randomized trial on diagnostic efficacy.

BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. PATIENTS AND METHODS: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.

Diagnostic quality of biopsy specimens: comparison between a conventional biopsy forceps and multibite forceps.

BACKGROUND: The endoscopic biopsy is a prerequisite for histopathologic diagnosis. Various types of forceps are used to obtain tissue specimens. The aim of this study was to assess and compare the diagnostic quality of biopsy specimens obtained with a conventional forceps and a Multibite forceps. METHODS: In a prospective, partially blinded, and randomized trial that included 250 patients referred for diagnostic upper and/or lower endoscopy, 510 biopsy specimens obtained with the Multibite forceps were compared with 520 specimens obtained with a conventional forceps. An experienced, blinded pathologist evaluated the specimens for diameter, depth of specimen, artifacts, anatomic orientation, vitality, general histologic quality, and diagnostic quality. Statistical analysis was performed by using the Fisher exact test. A p value of < 0.05 was regarded as significant. RESULTS: There were no statistically significant differences between the specimens obtained with the 2 forceps. The p values for the evaluated parameters were as follows: diameter 0.45, depth of specimen 0.56, artifacts 1.0, pathoanatomic orientation 0.40, vitality 0.45, and histologic diagnostic quality 0.53. CONCLUSION: The quality of biopsy specimens obtained with the Multibite forceps is comparable with that of specimens taken with a conventional forceps. Use of the Multibite forceps saves time in that 4 specimens can be obtained in 1 pass in situations in which a large number of specimens are needed or when the potential for transmission of infection is of concern.

Molecular typing of HLA-A, -B, and DRB using a high throughput micro array format.

The goal of this study was to develop a DNA micro array procedure for molecular human leukocyte antigen (HLA) typing of a large number of samples. DNA was isolated from peripheral blood samples and polymerase chain reaction (PCR) amplified for HLA-A, -B, and -DRB. Amplified DNA samples were spotted on silane-treated glass slides using a micro array spotter. The spotter was capable of spotting multiple slides with up to 9216 samples per slide or 2304 samples in quadruplicate. The allele specific oligo nucleotide probes for HLA-A, -B, and -DRB were labeled with the fluorescent dye Cy3, while a control probe, to quantitate the total amount of PCR product in a sample, was labeled with Cy5. Each slide was hybridized with a mixture of an allele specific Cy3 probe plus the control Cy5 probe. Following hybridization and wash, the amount of probe hybridizing to each DNA sample on the slide was measured with a micro array scanner. A computer program was used for image analysis, to calculate the average Cy3/Cy5 ratios and to identify the positive and negative samples. In turn, this information was used to determine the HLA phenotype of each sample. There was very good concordance between the results obtained for all three loci using Cy-labeled probes as compared with those previously obtained by chemiluminescent detection of alkaline phosphatase labeled probes. This methodology has the potential of greatly simplifying HLA molecular typing of large number of samples.

Cytomegalovirus-induced transient protein-losing hypertrophic gastropathy in an immunocompetent adult.

Transient protein-losing hypertrophic gastropathy with similarity to Ménétrier's disease is described. Acute infection with cytomegalovirus (CMV) could be shown to play a causative role. Immunodeficiency was ruled out. The 34-year-old patient had complete resolution of the disease without antiviral treatment. To our knowledge the present report is the first case of CMV-associated protein-losing hypertrophic gastropathy in an immunocompetent adult. To date, a similar disorder has only been described in children. CMV infection should be considered in patients with acute and symptomatic protein loss of gastrointestinal origin.

Peutz-Jeghers syndrome: is family screening needed?

In a 7-year-old boy, a small-bowel polyp was found intraoperatively as a lead point of an intussusception. Histologically, a hamartoma was found and the clinical work-up revealed Peutz-Jeghers syndrome (PJS). Additionally, all four asymptomatic siblings showed intestinal polyposis. All children in a family with PJS should be properly investigated. In case of an intussusception with a polyp in a critical location, a surgical procedure should follow.

Risk factor assessment of endoscopically removed malignant colorectal polyps.

BACKGROUND: Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. AIMS: To determine the significance of histological findings of patients with malignant polyps. METHODS: Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months). RESULTS: Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. CONCLUSION: As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk.

[Chronic giardiasis with intestinal dwarfism and delayed puberty in immunoglobulin deficiency syndrome: complete catch-up growth after therapy]. / Chronische Giardiasis mit intestinalem Kleinwuchs und Pubertas tarda bei Immunglobulinmangelsyndrom: vollständiges Aufholwachstum nach Therapie.

A 10-year-old, previously healthy Swiss boy suffered from repeated episodes of watery diarrhea for some months following a summer camp holiday. No etiology was found, and except for symptomatic treatment no other therapy was necessary. Five years later he was investigated because of growth failure, with a bone age of 11.5 years, but the correct diagnosis was not established. Only when he was reinvestigated at the age of 20 years, because of persistent growth failure and a bone age of 14 years, were Giardia lamblia trophozoites seen microscopically on the surface of duodenal mucosa biopsy specimens. At the same time dysgammaglobulinemia was detected which may have predisposed the gastrointestinal tract to chronic giardiasis. After a 10-day course of metronidazole the patient experienced catch-up growth and completed his pubertal development. The dysgammaglobulinemia persisted after therapy. This case showed that in patients with intestinal growth failure, catch-up growth and completion of pubertal development are possible even after the age of 20 years if nutritional supply is sufficient. Bone age determinations serve to indicate remaining growth potential.

A case of Erdheim-Chester disease with orbital involvement.

The Erdheim-Chester disease is a rare idiopathic, systemic, histiocytic disorder. To our knowledge, ocular involvement has been reported in only 16 cases. We describe a 55-year-old man who had symmetrical exophthalmos and several skin nodules on the arms and trunk. A magnetic resonance imaging scan confirmed the presence of bilateral, intraconal, retrobulbar tumors. An examination of the histopathologic features of orbital and skin biopsy specimens revealed xanthogranulomatous infiltrate with Touton giant cells. Further systemic investigations showed bone and retroperitoneal involvement. Three years later, multiple eyelid xanthelasmas developed in the patient. These findings are consistent with the diagnosis of the Erdheim-Chester disease. The patient's condition is stable under therapy with low-dose corticosteroids. His survival is longer than usually described in the literature.

[Filaria: a tropical disease as the etiology of acute scrotum]. / Filarien: eine Tropenkrankheit als Ursache für das akute Skrotum.

In the diagnosis and treatment of acute scrotal pain and swelling it is important to differentiate between testicular torsion and epididymo-orchitis. A special case of a thirty-eight-year-old male asylant from Nepal was presented in the urological service with acute scrotal pain. To exclude testicular torsion, a diagnostic exploration of the scrotum was done with the findings of an acute funiculitis with abscess formation. Under surgical drainage of abscess together with medical treatment the acute inflammation disappeared. The diagnosis of filarial funiculitis was made after identifying the microfilariae in a blood vessel and in the peripheral blood smear. A filaricide medication with diethylcarbamacine citran was administered with good symptomatic relief.

Familial glomerulopathy with giant fibrillar (fibronectin-positive) deposits: 15-year follow-up in a large kindred.

A 15-year clinical follow-up is reported for a familial glomerulopathy characterized on light microscopy by the glomerular deposition of giant fibrillary deposits (Virchows Arch A Pathol Anat Histol 388:313-326, 1980). On electron microscopy, the deposits consist of randomly oriented fibrils (12 to 16 nm in width and 120 to 170 nm in length). These deposits show positive immunoreactivity for fibronectin. One hundred fifty-seven of 197 family members within five generations were investigated. The disease is characterized by the occurrence of albuminuria in the third to fourth decades of life and slow progression to end-stage renal disease over a period of 15 to 20 years with the occurrence of generalized distal tubular acidosis (renal tubular acidosis type IV), hypertension, and the nephrotic syndrome. The frequent occurrence of otherwise unexplained microalbuminuria in young individuals of generations IV and V could be indicative of incipient glomerular disease. In one affected male individual and in his unaffected sister, renal cell carcinoma was diagnosed, raising the possibility that this familial glomerulopathy might be associated with an increased risk to develop renal cell cancer by direct or indirect (associated genetic predisposition) mechanisms. The disease relapsed in one renal transplant, raising the possibility of the presence of a transferable factor that could be part of the deposited fibrillar material or, alternatively, interfere with the glomerular handling of the deposited material.

Glomerulopathy associated with predominant fibronectin deposits: a newly recognized hereditary disease.

A newly recognized type of familial glomerulopathy observed in patients of both sexes in six families is reported. Proteinuria, often within the nephrotic range, microscopic hematuria, hypertension and a slowly decreasing renal function over several years were common. No underlying systemic diseases were identified. Generally, light microscopy showed enlarged glomeruli with minimal hypercellularity and with extensive deposits in the mesangium and subendothelial space. By electron microscopy, granular deposits with some admixture of fibrils were most common. In one family, the deposits were predominantly fibrillary. Immunoglobulins and complement factors were inconstant or lacking. A main finding was a strong immune reactivity to fibronectin, corresponding to the distribution of the deposits. In one patient, the deposits recurred in a renal transplant. There was no indication of systemic deposition. Abnormalities in the metabolism of circulating fibronectin may play a pathogenetic role in this disease of probably autosomal dominant inheritance.

[Case report: renal oncocytoma and Basedow hyperthyroidism]. / Fallbeschreibung: Renales Onkozytom und Basedow-Hyperthyreose.

Renal oncocytomas are reported as benign, rare neoplasms of the kidney. We describe a patient with renal oncocytoma and hyperthyreosis. Problems in diagnosis in radiology and pathology are described.

Frequency of restriction site polymorphisms in the region surrounding VNTR loci.

Variations in allele size in loci containing tandem repeats result from changes in the number of these repeats. However, digestion of the same DNA samples with two restriction enzymes (i.e. PstI and HaeIII), that have recognition sites predominantly in the DNA region flanking the VNTR, has identified the presence of numerous site polymorphisms. Three loci (D2S44, D4S163, D17S79) were examined for the presence of restriction site polymorphisms in both North American Black and Caucasian populations. At all loci there were alleles with site polymorphisms. This type of variations were more common in the North American Black than in the Caucasian populations.

Myoepithelial differentiation in benign sweat gland tumors. Demonstrated by a monoclonal antibody to alpha-smooth muscle actin.

One hundred and two cases of benign sweat gland tumors of the skin were studied for the presence of myoepithelial cells specifically identified by a monoclonal antibody to alpha-smooth muscle actin on paraffin-embedded tissues. The monoclonal antibody gave a positive result in 12 of 12 cases of cylindroma, 14 of 16 cases of spiradenoma, 2 of 2 cases of apocrine tubular adenoma (papillary eccrine adenoma), 5 of 5 cases of apocrine hidrocystoma, 5 of 5 cases of hidradenoma papilliferum, and in 10 of 10 cases of syringocystadenoma papilliferum. Rare myoepithelial cells were detected in only 1 of 10 cases of mixed tumor, apocrine type. There was no immunoreactivity for alpha-smooth muscle actin in eccrine hidrocystoma (2 cases), mixed tumor of eccrine type (2 cases), syringoma (7 cases), hidroacanthoma simplex (1 case), eccrine poroma (14 cases), clear cell hidradenoma (15 cases), and in 1 case of eccrine syringofibroadenoma. Our data support the concept that myoepithelial cells are seen in most sweat gland tumors considered to differentiate toward the secretory coil of the normal sweat gland. In contrast, myoepithelial cells are absent in tumors showing differentiation toward the excretory (ductal) component of the gland.

[Differential diagnosis of breast tumors with eczematous breast changes: two rare cases]. / Zur Differentialdiagnose von Mammatumoren mit ekzematösen Mamillenveränderungen: zwei seltene Fälle.

It is reported upon two patients who were presented to us to evaluate suspicious tumors of the breast: A 64-year-old patient had very painful tumors in both breasts measuring four centimeters in diameter with additional eczematous lesion of the left mamilla, which has developed within the last weeks. For many years she suffered of a pseudoxanthoma elasticum (PXE) of the skin combined with arterial occlusion disease. Histologically these tumors showed necrosis and typical signs of PXE, which is to our knowledge the first case reported in literature. A 79-year-old patient showed an inverted eczematous nipple, combined with a retromamillar painless tumor of the left breast. The histology was Paget's disease with an underlaying ductal carcinoma. --The clinical picture and the diagnosis are presented, followed by the discussion and the differential diagnosis.

Human population genetic studies using hypervariable loci. I. Analysis of Assamese, Australian, Cambodian, Caucasian, Chinese and Melanesian populations.

Population genetic studies, in Australian, Assamese, Cambodian, Chinese, Caucasian and Melanesian populations, were performed with several highly polymorphic DNA loci. Results showed that the Caucasian and Chinese had the highest level of heterozygosity. The size range of the majority of the polymorphic DNA fragments of a locus was the same in the different populations. The distinguishing feature of each ethnic group was the relative frequency of a particular set or group of alleles. For example, alleles greater than 9.0 kb in size, in D14S13, or from 4.5 to 4.7 kb, in D18S27, were less than half as frequent in Caucasians than in the other populations. Overall, there were groups of alleles, at one or more loci, whose frequencies were different among some of the ethnic groups and therefore could be used to differentiate one group from the other.