Deleted in Malignant Brain Tumors 1 is a versatile mucin-like molecule likely to play a differential role in digestive tract cancer.

Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a candidate tumor suppressor gene for brain, lung, and digestive tract cancer. In particular, alterations of the gene and/or a loss of expression have been observed in gastric, colorectal, and esophageal carcinomas. Initial evidence has accumulated that DMBT1 may represent a multifunctional protein. Because the consequences of a loss of DMBT1 function may be different depending on its original function in a particular tissue, we wondered if it is appropriate to assume a uniform role for DMBT1 in digestive tract carcinomas. We hypothesized that a systematic characterization of DMBT1 in the human alimentary tract would be useful to improve the understanding of this molecule and its role in digestive tract carcinomas. Our data indicate that the expression pattern and subcellular distribution of DMBT1 in the human alimentary tract is reminiscent of epithelial mucins. Bovine gallbladder mucin is identified as the DMBT1 homologue in cattle. An elaborate alternative splicing may generate a great variety of DMBT1 isoforms. Monolayered epithelia display transcripts of 6 kb and larger, and generally show a lumenal secretion of DMBT1 indicating a role in mucosal protection. The esophagus is the only tissue displaying an additional smaller transcript of approximately 5 kb. The stratified squamous epithelium of the esophagus is the only epithelium showing a constitutive targeting of DMBT1 to the extracellular matrix (ECM) suggestive of a role in epithelial differentiation. Squamous cell carcinomas of the esophagus show an early loss of DMBT1 expression. In contrast, adenocarcinomas of the esophagus commonly maintain higher DMBT1 expression levels. However, presumably subsequent to a transition from the lumenal secretion to a targeting to the ECM, a loss of DMBT1 expression also takes place in adenocarcinomas. Regarding DMBT1 as a mucin-like molecule is a new perspective that is instructive for its functions and its role in cancer. We conclude that DMBT1 is likely to play a differential role in the genesis of digestive tract carcinomas. However, although DMBT1 originally has divergent functions in monolayered and multilayered epithelia, carcinogenesis possibly converges in a common pathway that requires an inactivation of its functions in the ECM.

Prevalence of hereditary hemochromatosis in a Massachusetts corporation: is Celtic origin a risk factor?

The prevalence of homozygous hereditary hemochromatosis (HHC) is estimated at 1:250 in Caucasian adults. Little is known about ethnic subpopulations that might be at increased risk for this disease. HLA data have suggested a Celtic origin for HHC. Screening for HHC was offered to all employees of the Massachusetts Polaroid Corporation. Participants with a transferrin saturation of >55% or >45% and an elevated serum ferritin concentration on two screenings were referred for liver biopsy. The diagnosis of HHC was based on histological criteria, quantitative hepatic iron determination, hepatic iron index, and the phlebotomy requirement for iron depletion. Participants completed a questionnaire regarding their ethnic background. Two thousand two hundred ninety-four employees were screened, and 5 cases of HHC were detected. All 5 cases involved Caucasian men, yielding a prevalence of 1:395 for the Caucasian population. Four of the 5 cases were of 100% British-Irish ancestry based on the country of origin of their grandparents. Additional analysis revealed that the majority of grandparents of all 4 individuals came from Ireland or Wales. The exact two-tailed trend test showed a significant association of HHC with Celtic background (P = .012). The estimated cost of screening per patient identified was $18,041. Polaroid Corporation has a high representation of employees of British-Irish ancestry. Our data suggest that they are at high risk for developing HHC. A significant association of HHC with Celtic ancestry was found in this subpopulation, supporting the concept of a Celtic origin for this disease.

Sequence rearrangements in the upstream regulatory region of human papillomavirus type 6: are these involved in malignant transition?

Human papillomavirus type 6 (HPV-6) was isolated from a tongue papilloma which subsequently progressed to an invasive carcinoma. Three biopsies were taken from the same patient at different intervals during the tumour development. The HPV-6 genome in all three biopsies contained a GT-rich 94 bp insertion at nucleotide 7350 in the upstream regulatory region (URR). In comparison to previously published HPV-6 DNA isolates, this insertion seems to be the most prevalent and constant modification, not present in the prototype HPV-6b, and allows an improved alignment with the sequence of the HPV-11 genome. The possible biological significance of these GT-rich clusterings at the beginning of the URR, present not only in these HPV-6 isolates but observed in all other 'genital' HPVs also, is discussed.

[Malignant melanoma of the mucous membranes of the upper aerodigestive tract. Clinical, histological and immunohistochemical characteristics]. / Maligne Melanome der Schleimhäute des oberen Aerodigestivtraktes. Klinische, histologische und immunhistochemische Charakteristika.

Malignant melanomas of the mucous membranes are rare tumors. They make up about 10% of all malignant melanomas of the head and neck; 15 of the authors' cases are reviewed in this article. Six of these had neck lymph node metastasis when first diagnosed. The tumors were surgically removed in all patients. Thirteen patients developed at least one tumor recurrence, ten patients distant metastasis. Eight patients died of the tumor condition; the mean survival time of all patients was 33.4 months. While the tumors could be classified histologically into four types, this had no bearing on the course of the disease. In many cases, primary tumor and metastasis or recurrent tumor differed histologically. Melanin pigment was found in 13 tumors. Mucosal melanomas can be regarded as a discrete tumor entity because their biological behavior differs from that of malignant melanomas of the skin. However there are no morphological differences between the two tumor entities. Ophthalmological and dermatological examinations must be performed in all patients with mucosal melanoma to exclude metastasis of the skin or choroid melanoma.

[Pedicled small intestine segment for circular replacement of the extrahepatic bile duct in preserved papillary passage. An animal experiment study]. / Ein gestieltes Dünndarmsegment zum zirkulären Ersatz des extrahepatischen Gallengangs bei erhaltener papillärer Passage. Eine tierexperimentelle Untersuchung.

The effect of a small bowel segment as a extra-hepatic bile duct replacement was examined in 12 pigs followed-up for a period of 420 days. No complications, either during the operation or postoperatively, were observed in any of the animals. The laboratory parameters were within normal range over the entire observation period of 420 days. After 2, 6, and 12 months there was no anastomotic stenosis in the PTC. The intrahepatic biliary tract was not dilated. There was obvious peristalsis of the small bowel transplant towards the papilla of Vater. The autopsy showed that the grafts had healed without any sign of irritation. Histologically the structure of the graft remained undisturbed. There was a clear distinction between the mucosa of the bile duct and that of the small bowel, with no sign of a chronic infection. In the graft as well as in the vascular pedicle the nerve fibres were intact. Liver biopsy showed no pathological changes. In the light of these experiments, a small bowel segment presents a very promising alternative replacement of the extrahepatic biliary tract.

[Animal experiment studies of pedicled small intestine transplantation as partial extrahepatic bile duct replacement]. / Tierexperimentelle Untersuchungen zum gestielten Dünndarmtransplantat als partieller extrahepatischer Gallengangsersatz.

A pedicle graft of the jejunum can in some cases enlarge a bile duct stricture. The enlargement of the patch and its consequences on the liver function are possible problems. In an animal experiment the following questions were sought. 1) Is a partial replacement of the bile duct with a pedicle graft of small bowel possible? 2) Is there an enlargement of the patch in every case and what are the consequences on the biliary tract and on liver function. The experiments were performed on 14 minipigs over a long-term observation period of 450 days. The red and white blood cell count, the GPT, GOT, GPT, bilirubin and alkaline phosphatase and copper were checked monthly. After 2, 6 and 12 months the intra- and extrahepatic biliary tract were visualized via a PTC. After 8 months an angiography of the pedicle graft was performed. 15 months later the animals were killed and the bile duct, the graft and the liver were histologically examined. 1) With a pedicle graft of small bowel a partial replacement of the extrahepatic bile duct is possible. 2) An enlargement of the patch is seen in every case. The enlargement is a consequence of tension at the pedicle. After 15 months no morphological changes were observed at the patch nor were there any irregularities in liver function.

[Therapy and prognosis of medullary thyroid cancer]. / Therapie und Prognose des medullären Schilddrüsenkarzinoms.

Medullary thyroid cancers have different morphological, endocrine and biological qualities than all the other tumors of the thyroid. Therapy is the thyroidectomy with modified, radical neck dissection. The ten year survival rate was 65% in our own patient material. The prognosis depended on tumor size, invasion of vessels by the tumor, grade of differentiation, tumor stage, metastasis and radicality of the operation.

Relevant factors in the prognosis of ductal pancreatic carcinoma.

Because it is important to assess relevant prognostic factors when deciding which patients will profit from pancreatic resection and which will not, 484 patients with ductal pancreatic carcinoma who were operated on between 1 January 1978 and 31 December 1987 in the Department of General and Abdominal Surgery of Mainz Medical School were studied retrospectively. Prognostically favourable factors were: a history of 8 weeks or less, the presence of jaundice, the absence of back pain, a well to moderately differentiated carcinoma, a tumour less than 3 cm in diameter, a preoperative CA19-19 value of less than 400 U/ml, and no sign of lymph node metastases or other metastatic spread. Only 19 patients (3.9%) satisfied these criteria. Our objective is to now check these results in a prospective study with a larger number of patients and, in addition, to compare the quality of life of patients who were treated by resection with that of those who received palliative treatment.

[Resorbable staple sutures for partial stomach and duodenal stump closure. Animal experiment studies]. / Resorbierbare Klammernähte zum partiellen Magen- und Duodenalstumpfverschluss. Tierexperimentelle Untersuchungen.

In two groups of pigs, 10 in each, partial gastrectomies with gastroduodenostomy (Billroth I) respectively gastrojejunostomy (Roux-en-Y) were performed. Absorbable lactomer (Polysorb, Auto-Suture) staple lines--a copolymer of glycolic acid/lactic acid-, used for the closure of the lesser curvature of the stomach and the duodenal stump, were safe. No suture dehiscence was observed. Macroscopic examination showed no major inflammatory adhesions around the staples. Microscopically inflammatory reactions around the staples in the gastrointestinal wall were found. Our results yielded no contraindication for clinical tests of absorbable sutures in gastrointestinal surgery.

[Prognostically relevant factors in follicular thyroid cancer]. / Prognostisch relevante Faktoren beim follikulären Schilddrüsenkarzinom.

The discussion of the prognosis of follicular thyroid carcinoma is controversial. To evaluate the factors which influence the prognosis we retrospectively analyzed our patients from 1. 1. 1964 to 31. 12. 1987. 76 patients with a follicular thyroid carcinoma were treated during this time. Factors influencing the prognosis were: (1) multiple tumor growth; (2) pT-classification; (3) vascular invasion; (4) tumor stage; (5) degree of cellular differentiation and (6) metastases. Because of the prognostic influence of multiple tumor growth and the slight prognostic influence of lymph node metastases we recommend a total thyroidectomy with neck dissection for follicular thyroid carcinoma.

[Prognostically relevant factors in ductal pancreatic cancer]. / Prognostisch relevante Faktoren beim duktalen Pankreascarcinom.

Prognosis of patients with pancreatic carcinoma is bad. Less than 1% of all patients and even after pancreas resection only 10% survive more than 5 years. To evaluate the factors which influence the prognosis we analyzed retrospectively all patients who were operated on a pancreas cancer (n = 484) from January 1, 1978 to December 31, 1987. Age, sex, perineural invasion and lymphangiosis carcinomatosa had no prognostic influence. The duration of symptoms, degree of cellular differentiation, tumor size, preoperative level of the tumor associated antigen CA-19-9, nodal involvement and stage were statistically significant for prognosis. R1 and R2-resections had no better prognosis than other palliative procedures.

[Keratocysts of the maxilla and zygoma. Case report and review of the literature]. / Keratozysten des Oberkiefers und des Jochbeins. Fallvorstellung und Literaturübersicht.

Keratocysts are a special entity of jaw cysts. The horizontal and distal regions of the mandible and the ascending ramus of the mandible are the most common locations of these cysts. Keratocysts of the os zygomaticum and orbital floor are extremely rare. In case of infection radiologic and histologic diagnosis are difficult and these cysts are often misdiagnosed as radicular and follicular cysts. The case of a 49-year old man is reported, who was admitted to hospital suffering from recurrent episodes of maxillary sinusitis with orbital involvement. He had previous sinus surgery six times. The clinical, histologic and radiologic characteristics are reported. In a literature review the present case is discussed. Because the recurrent-rate of keratocysts is rather high, complete removal and careful post-operative follow-up are mandatory.

Progressive papillomatosis of the intrahepatic and extrahepatic bile ducts. Case report.

Papillomatosis of the bile ducts is uncommon, with only 26 cases in the available literature. The salient symptom is icterus, often with right-sided abdominal pain. Endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography nowadays permit preoperative diagnosis. Complete removal should be the aim, because of the tendency to continuous growth, intrahepatic spread and malignant degeneration. Four cases are presented.

[Progressive papillomatosis of the intra- and extrahepatic bile ducts]. / Die progressive Papillomatose der intra- und extrahepatischen Gallenwege.

The papillomatosis of the bile duct may occur at any age but more often at the age of 40 and 50 with a slight preference for men. The main symptom is an icterus often combined with right-sided epigastric pain. ERC and PTC allows the preoperative diagnosis on the basis of the typical clinical picture. The papillomatosis of the bile duct has to be considered as a disease with cancer risk. The prognosis in case of incomplete removal is unfavorable because of the continuous growth, the intrahepatic spread and the elevated degenerative tendency. Therefore a complete removal should be considered.

[Prognostically relevant factors in cancer of Vater's ampulla]. / Prognostisch relevante Faktoren beim Carcinom der Papilla Vateri.

In order to evaluate the relevant factors for prognosis for patients with cancer of Vater's papilla our own patient material between 1. 1. 1978 and 31. 12. 1987 was studied retrospectively. The influence of age, sex, duration of anamnesis, tumor size, tumor morphology and tumor stage on the prognosis were analyzed in 32 patients with cancer of Vater's papilla. The 5 year survival rate after Whipple procedure was 56.1%. Statistically significant factors for prognosis were tumor size, lymph node metastases and tumor stage.

[Clinical pathology of the glomerulus--from phenomenon to entity. The minimal glomerular lesion]. / Klinische Pathologie des Glomerulus--vom Phänomen zur Entität. Die minimale glomeruläre Läsion.

There are several clinical conditions which can induce minor glomerular lesions. Clinical symptoms range from severe proteinuria with nephrotic syndrome to slight hematuria with or without proteinuria. There are two principal morphological conditions associated with minor glomerular lesions: 1. The initial stage of glomerulopathies. 2. Stable minor glomerular lesions, which have not changed their appearances for years. Ad 1.: Regarding severe proteinuria, there are two possible causative conditions: membranous glomerulonephritis stage I (according to EHRENREICH and CHURG), or the initial stage of amyloidosis. Recurrent hematuria may result from hereditary nephropathy of Alport's syndrome. Ad 2.: Non-evolving minor glomerular lesions with symptomes of severe proteinuria can be defined as so-called minimal change nephropathy. Under certain conditions, morphology of minor glomerular lesions can result from focal and segmental sclerosis. Concerning hematuria, minimal glomerulonephritis (diagnosed by immunofluorescence) and benign familial hematuria (diagnosed by electron microscopy) must be differentiated. The two above-mentioned conditions are discussed in terms of the triple diagnostic procedures of light microscopy, immunofluorescence and electron microscopy. For diagnosing minor glomerular lesions, it is recommended to use frozen sections instead of paraffin embedded, which can give false negative results.

[Primary larynx carcinoid. Case report and review of the literature]. / Primäres Larynxkarzinoid. Fallvorstellung und Literaturübersicht.

Neuroendocrine tumours of the larynx are extremely rare. Only 20 cases of laryngeal carcinoid tumours have been reported. Since histological diagnosis is difficult, this unusual neoplasm was often misdiagnosed as an undifferentiated carcinoma. The case of a 72-year old man is reported, who was admitted to hospital after suffering from hoarseness and left-sided otalgia for 4 weeks. Indirect laryngoscopy showed a tumour at the left ary region. The tumour was removed endoscopically. The light and electron microscopic characteristics and the results of the histochemical examinations are reported. In a review of the literature, the data of the 19 previously published cases are discussed together with those of the present case.

[Tumors of the ceruminous glands]. / Tumoren der Ceruminaldrüsen.

Tumours originating from the ceruminous glands can be classified into five types: adenomas, adenocarcinomas, adenoid-cystic carcinomas, pleomorphic adenomas and mucoepidermoid carcinomas. The diagnosis is based on histological findings and can be quite difficult if the tumour status has to be determined. Classification into one of the five types of tumours may be facilitated at times by studying the clinical pattern. Three case reports are quoted as examples to illustrate that neoplasias originating from the ceruminous glands can assume considerable proportions and must be considered in differential diagnosis when assessing space-occupying growths in the soft tissue of the neck. Whereas prognosis of adenomas and pleomorphic adenomas can be considered to be good, it must be regarded as likely to be infaust in the case of adenocarcinomas, adenoid-cystic carcinomas and mucoepidermoid carcinomas. The use of cytostatics resulted in a marked reduction of the tumour in one of the described cases of adenocarcinoma.