Cancer of the oesophagus

Oesophageal cancer is the fourth most common tumour in developing countries, comprising mainly squamous cell tumours, although the incidence of adenocarcinoma has increased enormously over the last decades. Surgical resection has long been acknowledged as the mainstay of treatment, and developments in surgical technique are reviewed. The roles of radiotherapy and chemotherapy in the management of oesophageal cancer remain unclear, especially as the majority of studies to date have been uncontrolled trials. We present an analysis of 601 patients who underwent resection for carcinoma of the oesophagus between 1970 and 1994 in the Department of Clinical Surgery, St James's Hospital, Dublin. The analysis shows clearly that, while peri-operative mortality continues to improve, conventional surgery offers little prospect of cure in the majority of cases. We have therefore embarked upon a prospective controlled trial of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell tumours of the oesophagus. Preliminary results indicate that multi-modality treatment may have a valuable role to play in the treatment of carcinoma of the oesophagus.     

Detection of human papillomavirus DNA with in situ hybridisation in oral squamous carcinoma in a rural black population

Intra-oral carcinoma is the third most common malignancy among men in developing countries, and carries a high mortality rate, particularly in Africa, where patients often present initially with lesions at an advanced stage. The present study was undertaken to determine the prevalence of human papillomavirus (HPV) DNA in oral squamous carcinoma in the west of the Northern Transvaal, an area where a large number of new cases has been diagnosed over the past few years. Paraffin blocks from 66 cases (51 men, 15 women; mean age 58.7 years) of oral squamous carcinoma were randomly selected. Blocks contained samples of both tumour and adjacent normal epithelium. The presence of HPV antigen was established by means of immunocytochemistry and HPV DNA by in situ hybridisation with radiolabelled probes for HPV-6, 11, 16 and 18. Immunocytochemistry for viral antigen was negative in all the specimens. HPV-18 was detected in normal epithelium adjacent to the tumour in one case only. It appears from our study that HPV is of limited importance in oral squamous cell carcinogenesis in the population studied.     

Schistosomiasis and carcinoma of the bladder in Zambia

Carcinoma of the bladder is the third most important malignancy seen in Zambia, accounting for nearly 9% of all malignancies seen in the Department of Pathology at the University of Zambia. A review of 217 cases of carcinoma of the bladder seen in the department over a 5-year period revealed a preponderance of well-differentiated squamous cell carcinoma (75%). Of the 217 cases, 65% had concomitant schistosomiasis. These tumours tended to occur in a younger age group than that reported from England and North America. The pattern of pathology conforms with that reported from other parts of Africa with hyperendemic and endemic schistosomiasis. The aetiological role of schistosomiasis in bladder cancer is critically examined.     

Effects of incubation temperature on the energetics of embryonic development and hatchling morphology in the Brisbane river turtle Emydura signata

AIMS: To investigate the malignant potential of lichen sclerosus, a study using the cell proliferation marker Ki67 comparing lichen sclerosus with and without associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated carcinoma, and 31 cases without associated carcinoma, including 16 random cases, seven with epidermal thickening and eight with epidermal thinning, were examined by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67 reactivity was mostly seen in the basal and parabasal cells in both groups of lichen sclerosus and this pattern was similar to normal skin, squamous cell hyperplasia and analogous to that of one form of squamous cell carcinoma. There was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with associated squamous cell carcinoma; however, in squamous cell hyperplasia adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In lichen sclerosus without associated carcinoma, the random cases had a count of 53 per 100 basal cells, those with epidermal thickening 53 and those with thinning 42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION: The lack of qualitative differences of Ki67 expression in normal skin, in lichen sclerosus with and without carcinoma, in squamous cell hyperplasia and in one form of squamous cell carcinoma indicates that these conditions share a common localized pattern of cell proliferation and does not support or deny the malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened lichen sclerosus compared to thinned suggests that some or all of the cases of thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia or that lichen simplex chronicus superimposed on lichen sclerosus has a higher Ki67 expression or that the distinction between squamous cell hyperplasia and lichen simplex chronicus is only one of terminology.     

A comparison of three different dihydroartemisinin formulations for the treatment of acute uncomplicated falciparum malaria in Thailand

This study was aimed at assessing the response to electrochemotherapy with cisplatin of cutaneous tumour nodules in patients with malignant melanoma, squamous cell carcinoma and basal cell carcinoma. In 4 patients, 30 tumour nodules of different sizes were treated; five without treatment, one with electric pulses, five with cisplatin injected intratumorally and 19 with electrochemotherapy, i.e. intratumoral administration of cisplatin followed by delivery of electric pulses to the tumour nodule. After 4 weeks, a complete response (CR) in all 19 electrochemotherapy treated nodules was obtained. All electrochemotherapy treated nodules remained in CR (range 7-11 months), regardless of histological type, except for the metastasis of a squamous cell carcinoma that progressed after 9 months. CR was also obtained in two of five tumour nodules treated with cisplatin intratumorally, but the other three nodules progressed within 3-7 months. Exposure of the tumour nodule to electric pulses without cisplatin treatment had no effect on tumour growth. Electrochemotherapy was well tolerated by all patients and a good cosmetic effect was obtained, with only minimal scarring and a slight depigmentation of the skin. Electrochemotherapy with cisplatin has proved to be effective in patients with cutaneous tumour nodules. Furthermore, electrochemotherapy is easy to perform and can be carried out on an out-patient basis.     

Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an aortoesophageal fistula

Squamous cell carcinoma of the tonsil has a relatively poor prognosis. Aggressive surgery, radiation therapy and combinations of irradiation and surgery have been employed but there exists some controversy about the efficacy of these treatment modalities. The purpose of this paper is to compare the efficacy of treatment between the surgery followed by radiation therapy and the preoperative radiation therapy followed by surgical resection. The medical records of 33 patients treated for squamous cell carcinoma of the tonsil at the Department of Otolaryngology-Head and Neck Surgery, Korea University Hospital between 1989-1993 were reviewed retrospectively. None of the patients were stage I, but stage II, III, and IV were four, five, and 24 patients, respectively. There were 30 males and three females. The most common histopathology was moderately differentiated squamous cell carcinoma (20/33). The 13 patients treated initially with surgery had an overall three-year survival rate of 38.5%, and the rate for the 20 patients treated initially with radiation was 40%. The main pattern of treatment failure was a local recurrence and neck metastases, and pathologic differentiation thought to be an important prognostic factor. Complications are fewer in patients treated initially with surgery (23.1%) than patients initially treated with radiation (50.0%). There is no difference in the efficacy between the two therapeutic groups.     

Painful ophthalmoplegia following treated squamous carcinoma of the forehead. Orbital apex involvement from centripetal spread via the supraorbital nerve

Intraneural and perineural spread of squamous carcinoma from the face to the cranial cavity is an important cause of delayed cranial nerve palsies after local excision of a skin tumour. As exemplified in reports of two cases, signs of this type of centripetal spread of squamous cell tumour along the branches and trunk of the supraorbital nerve are (i) severe unremitting orbital and forehead pain with associated hypoaesthesia, (ii) palpable or radiological evidence of thickening of the nerve at the supraorbital notch and (iii) evolution of ophthalmoplegia, blindness, and sensory loss in the first division of the trigeminal nerve. Appearance of severe supraorbital neuralgia months or years after excision of a skin tumour from the forehead should alert the clinician to extension of tumour cells along the supraorbital nerve. This may enable him to institute timely treatment before a complete orbital apex syndrome has developed.     

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

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

Nutritional status of participants in the Giessen Senior Long-Term Study with respect to antioxidant vitamins and selenium

The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression.     

Verrucous carcinoma of the oral cavity: management by radiotherapy and surgery

Verrucous carcinoma is a distinct nonmetastasizing variant of well differentiated squamous cell carcinoma. It is frequently found in the oral mucosa, often in association with the more common type of metastasizing squamous cell carcinoma. In many centres radiotherapy is not used to treat verrucous carcinoma because this tumour is thought to be radioresistant and because "anaplastic transformation" has been reported following such therapy. In a series of 37 patients, 30 received radiotherapy, either alone or combined with surgery. Anaplastic transformation was not encountered. The best results were obtained with aggressive treatment which included both surgery and radiotherapy.     

Bacterial production and purification of the fish pituitary hormone somatolactin

Paraffin sections from 29 lung carcinomas (28 primary and 1 metastatic) and 9 pleural malignant mesotheliomas were immunostained with antisera to human hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, met. For HGF/SF, immunoreactivity was demonstrated in all 9 mesotheliomas, 9 of 12 adenocarcinomas, and 7 of 10 squamous cell carcinomas. None of seven cases of small cell anaplastic carcinoma was positive. The adenocarcinomas frequently showed enhanced luminal staining, suggesting possible secretion of HGF/SF, and this pattern of staining was also seen occasionally in bronchial epithelium adjacent to the tumour. Stromal fibroblasts also showed immunoreactivity for HGF/SF in 6/8 cases of mesothelioma but in only 3/12 adenocarcinomas, 1/10 squamous cell carcinomas, and 1/4 small cell anaplastic carcinomas. All tumours stained for met, usually strongly. The staining was mainly cytoplasmic in nature, but some plasma membrane staining was usually evident. Adenocarcinomas showed strong luminal membrane staining, as did adjacent, histologically normal bronchial epithelium. This study demonstrates the presence of HGF/SF and met in most of the tumour types described, particularly mesotheliomas, and suggests that the HGF/SF/met signalling system may play a role in the development of these tumours, either by autocrine or by paracrine mechanisms.     

Photochemotherapy--psoralen + UV-A (PUVA)--increased risk of cancer?

Photochemotherapy with psoralens + ultraviolet (UV)-A light (PUVA) has been used for about 16 years to treat psoriasis. Some reports have indicated a higher frequency of cutaneous squamous cell carcinoma among treated patients. The results are not consistent, however, and are not generally conceded. Our material from Ullev?l Hospital comprises 585 patients who have been treated with PUVA from 1977 until 1991. Three patients developed cutaneous squamous cell carcinoma, but in one of them the tumour developed before start of PUVA treatment. The two others had received only very small doses. One of them had an intraepithelial cancer of the penis. In addition we registered various internal cancers in 25 patients. The Norwegian Cancer Registry compared our patient materiel with a matched control group as regards sex, age and age-specific incidence rate. There was no statistically significant difference in incidence between the patient and the control group.     

Drug resistance to 5-aza-2''-deoxycytidine, 2'',2''-difluorodeoxycytidine, and cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine deaminase cDNA into murine cells

Squamous metaplasia can be demonstrated in about 4% of all invasive carcinomas of the breast. Primary squamous cell carcinomas of the breast are rare, since they occur in less than 1% of all primary invasive breast carcinomas. In order to classify a breast tumor as a primary squamous cell carcinoma one must exclude an epidermal origin, especially from the nipple region and the possibility of metastatic infiltration of the breast by a squamous cell carcinoma from a different location. Causative and formal pathogenesis of primary squamous cell carcinoma of the breast is not clear. A pluripotent embryonal stem cell origin is discussed, considering the phylogenetic descent of the mammary gland from skin appendages. Squamous metaplasia is also suggested to be a precursor of squamous cell carcinoma. Here endocrine stimulation and chronic inflammation may both play an inductive role. The number of published cases of squamous cell carcinomas developing years and decades after implantation of silicon prostheses has increased in recent years. These tumors probably develop on top of squamous metaplasia induced by the inflammatory pseudocapsule. Estimating the prognosis and therapeutic management in patients with squamous cell carcinoma of the breast should follow the same guidelines as for other squamous cell cancers.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Changes in pain sensitivity during neurosis in rats]

OBJECTIVE: Few cases of verrucous carcinoma of the penis with foci of invasive squamous cell carcinoma have been reported and denominated "hybrid tumors". The accuracy of this term is discussed in this paper. METHODS/RESULTS: A huge penile mass in a patient that had undergone three previous operations for lesions diagnosed as verrucous carcinoma is reported. Partial penectomy was performed. Histological examination showed a very well-differentiated squamous cell carcinoma. PCR (polymerase chain reaction) did not detect any type of human papillomavirus (HPV) in the tumor. CONCLUSIONS: Verrucous carcinoma is a strictly-defined lesion with a different biological behaviour from that of squamous carcinoma. Preoperative deep biopsy may miss the squamous cell carcinoma. Definitive diagnosis can only be achieved by histological examination of the surgical specimen. In future, DNA studies could possibly support preoperative diagnosis of this lesion.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.     

Genomic imprinting in the brain

Biopsies of cervix uteri from 166 patients with benign and malignant lesions (12 normal, 48 inflammatory lesion, 6 adenocarcinoma, 2 adenosquamous carcinoma and 98 from squamous cell carcinomas) were studied histochemically. The stains used were PAS with/without diastase, AB/PAS (pH 2.5) and OR/AB. In inflammatory lesions neutral mucin was predominent which was replaced by sialomucin and sulphomucin in endocervical polyps. In malignant lesions sulphomucin was predominent. Seventeen percent cases of squamous cell carcinomas needed reclassification after mucin staining. Of the fourteen large cell non-keratinizing squamous cell carcinomas, 12 were reclassified as squamous cell carcinoma with mucin secretion and 2 as adenosquamous carcinoma. One case of small cell non-keratinizing squamous cell carcinoma was reclassified as moderately differentiated adenocarcinoma. None of the keratinizing carcinomas had evidence of mucin secretion. Mucin histochemistry should be done routinely on non-keratinizing squamous cell carcinomas to pick up more cases of carcinoma with evidence of mucin secretion which can be missed on routine haematoxylin and eosin stains. Such carcinomas are known to pursue a more aggressive clinical course and have a poorer prognosis than non-mucin secreting type of squamous cell carcinoma.     

Localized amyloidosis in squamous cell carcinoma of uterine cervix: electron microscopic features of nodular and star-like amyloid deposits

An ultrastructural study of amyloid deposits in four cases of squamous cell carcinoma of uterine cervix was performed. The amyloid deposits reacted with anti-keratin antiserum on frozen sections. Amyloid deposits showed nodular (4 cases) and star-like forms (3 cases). Nodular amyloid deposits were composed of slightly whorled fibrils, measuring 7-10 nm in width. Some of them contained cellular debris and thicker, more electron-dense filaments than amyloid fibrils. In three cases, filamentous tumour cells and filamentous masses were observed together with amyloid. Star-like amyloid deposits were composed of bundles of straight amyloid fibrils. Some of the tumour cells in contact with star-like amyloid deposits had deep cytoplasmic invaginations, where closely packed amyloid fibrils were arrayed in parallel fashion. In addition, a few tumour cells had membrane-bound amyloid fibrils in the cytoplasm. It is suggested that nodular amyloid deposits are derived from the tumour cells through filamentous degeneration. Amyloid fibrils in star-like amyloid deposits are thought to be formed within the cytoplasm or in the vicinity of invaginated cytoplasmic membranes of the tumour cells.