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Alcohol, immunomodulation, and disease.

Recent research findings point to a spectrum of alcohol-induced immune dysfunctions in animal models and humans. Use of alcohol in vivo causes abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity, including lymphocytes, Kupffer cells and other macrophages, as well as the endothelium of blood vessels and lymphatics. Regulatory cytokines and neuroendocrine factors can mediate some of these immunomodulatory effects which may be further re-phased, exaggerated or unbalanced by other drugs of misuse. A variety of animal models is available to study acute and chronic alcoholism, non-alcohol drug misuse, AIDS as well as other opportunistic infections, and neoplasias, which hold promise of clarifying the role of alcohol as an immunomodulator.

Acquired Immunodeficiency Syndrome↗

Lymphadenopathy as a primary presenting sign: a clinicopathological study of 228 cases.

A total of 228 cases of lymphadenopathy as a primary presenting sign are reported. Tissue diagnoses were divided into: metastatic carcinoma (41 per cent), lymphoma (19 per cent), a specific non-neoplastic condition (10 per cent) and non-specific hyperplasia and inflammation (30 per cent); thus the overall yield of positive tissue diagnosis was 70 per cent. Just 5 primary sites: breast, lung, gastrointestinal and genito-urinary tracts and skin (mainly melanomas) accounted for all but one case. Hodgkin's and non-Hodgkin's lymphomas were evenly distributed. In those with generalized malignant lymphadenopathy a surprisingly even proportion of 1 to 1.5 was found between carcinoma and lymphoma. In those with localized malignant disease metastatic carcinoma predominated. The overall incidence of primary lymphadenopathy in increased with age, due to an increase in malignancy. Less than half of patients with carcinomatous lymphadenopathy had symptoms and these tended to be organ specific, whereas three-quarters of patients with lymphoma had symptoms which were usually non-specific. A haematological screen, liver function tests and chest X-ray were frequently abnormal but were not diagnostic.

Adolescent↗

Pathosis of the hard and soft palate.

In this article a few of the more recently emphasized and pertinent conditions that may affect the hard and soft palate have been discussed. The purpose of the article is not to present in all-inclusive classification of lesions occurring the palate. Disease of the palate may be local in nature or may reflect a systemic condition. Dentists must be conscious of the palate as the site of many possible pathoses. The prosthodontist in particular must observe and carefully evaluate the palate and insure its good health before he can prescribe a prosthesis to cover it. Dentistry provides a health service which affects the entire human organism and not just the oral cavity. Therefore an understanding of the varied nature of pathosis as it relates to the oral cavity, and especially the palate, is essential. Continuous surveillance of the palatal regions insures that the dentist's obligation to detect oral abnormalities in patients is in large measure fulfilled.

Ameloblastoma↗

Transrectal aspiration biopsy versus transperineal core biopsy for the diagnosis of carcinoma of the prostate.

Transrectal aspiration and transperineal core biopsies were performed on 38 patients with suspicious prostatic examinations. The false negative rate was 14 per cent by the core method but no cancer was missed by the aspiration technique. There was insufficient material for diagnosis in 14 per cent of the biopsies obtained by the core technique but in only 3 per cent with the aspiration biopsy method. Malignant cells were confirmed by cytology in 1 patient who had had 2 normal core biopsies. The cytological grade was only moderately consistent with the Gleason sum. No complications developed after either procedure. Transrectal aspiration biopsy offers several advantages over conventional biopsy methods and should be used regularly to diagnose abnormalities of the prostate.

Adenocarcinoma↗

Fatal generalized BCG histiocytosis.

An infant was vaccinated at the age of 3 days with BCG vaccine. At the age of 3 years 10 months he developed an infection by Salmonella typhimurium. The infection persisted with recurrent episodes of fever, peri-nephritic abscess, abscesses of lymph nodes, hepatomegaly, splenomegaly and paravertebral and retro-peritoneal abscesses, from which Salmonella were isolated. At the age of 6 years and 2 months later. At post-mortem examination there were widespread histiocytic nodules in many organs, from which Mycobacterium bovis BCG were cultured. One previous case has been reported from Czechoslovakia. The mother of that child was the sister of the father of the child reported here. It was not possible to investigate the possibility of abnormalities of humoral or cellular immunity in the family.

BCG Vaccine↗

Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

Carcinoma, Non-Small-Cell Lung↗

Metastatic prostatic carcinoma to supradiaphragmatic lymph nodes. A clinicopathologic and immunohistochemical study.

We identified 26 cases of metastatic prostatic carcinoma in supradiaphragmatic lymph nodes from 1972-1987. All involved nodes (15 supraclavicular, eight cervical, two axillary, and one mediastinal) were taken from the left side. Of those cases with available data, serum acid phosphatase was normal in five of 21 (24%). Seven of 20 (35%) had no evidence of bone metastases. Rectal examination was normal in eight of 19 cases (42%). While seven cases had a history of prostate cancer, the rest presented with enlarged nodes alone or with simultaneous urinary obstructive symptoms. Eighteen patients died following node biopsy (mean 19.8 months, range 1-46 months). Twenty-two of 26 metastases were high grade and often were not histologically suggestive of prostate carcinoma. In general, immunohistochemical staining for prostate-specific acid phosphatase (PSAP) was more intense than for prostate-specific antigen (PSA), in contrast to several other reports using these antisera. Metastatic prostate carcinoma should be ruled out by using immunoperoxidase for PSA and PSAP in all men over 45 presenting with carcinoma of unknown primary origin in left-sided supradiaphragmatic lymph nodes, even in the absence of bony disease, elevated serum acid phosphatase (SAP), abnormal rectal examination, and a histologic picture suggesting prostate carcinoma.

Aged↗

Distant metastases from lip and oral cavity cancer.

Distant metastases related to lip carcinomas occur very exceptionally (0.5-2%) and can be expected in cases of advanced tumors with advanced regional disease. Distant metastases from oral cavity carcinomas vary over a broad interval (8-17%) and depend also on the stage of disease. The knowledge of the presence of distant metastases is vital for the planning of further treatment. From a clinical point of view, patients with lip and oral cavity can be divided into a group where the risk of distant metastases is low, and into a high-risk one. In low-risk group patients (stages I, II and III) the risk of the incidence of distant metastases is 3%, and the diagnostic approach should consist of an X-ray of the lungs and liver tests. Further examinations are necessary if there are symptoms suggesting the presence of distant metastases or previous examinations are abnormal. The high-risk group (stage IV) and all patients with locoregional relapse have a risk of distant metastases of approximately 10% and the best treatment consists of a positron emission tomography (PET) scan. If a PET scanner is not available it is recommended to run a computed tomography scan of the lungs and liver tests. If any clinical investigation is abnormal further tests are necessary.

Bone Neoplasms↗

What to do if the lymph nodes are positive.

Lymph node metastases are common in patients with advanced bladder cancer. Survival rates have apparently improved from about 15% to 30% as management evolved from lymphadenectomy plus cystectomy to multimodal therapy, but investigators have not conclusively shown the benefit of adjuvant irradiation and/or chemotherapy. If clinical staging indicates nodal metastases, we recommend primary multiagent chemotherapy with subsequent exploratory laparotomy, lymphadenectomy, and possibly cystectomy for complete responders. Patients without clinical evidence of metastases undergo complete bilateral pelvic lymphadenectomy plus cystectomy if nodes are normal, or if grossly abnormal but resectable. Patients with nodal metastases may be candidates for adjuvant chemotherapy.

Combined Modality Therapy↗

Serum amylase in peptic gastroduodenal perforation. A study to determine the significance of abnormally high levels.

Elevated serum amylase is a frequent concomitant of perforated gastroduodenal ulcer. To determine if there might be significant correlation between an increase in amylase and some of the other factors associated with ulcer perforation, a study was made of the clinical records of 1,000 patients with perforation of gastroduodenal ulcers. Sixteen per cent of the patients had amylase levels of 200 Somogyi units or more. This rise in serum amylase comes about in cases of perforated peptic ulcer as a result of peritoneal lymphatic absorption of fluid containing pancreatic enzyme which is spilled through the perforation. Among patients with perforated ulcers and elevated serum amylase levels, the higher the amylase level, the higher the mortality rate. The factors of amount of abdominal fluid spill, the duration of the perforation before surgical closure, the size of the perforation, shock and recent ingestion of food were also studied for possible relationship with elevated serum amylase. All appeared to be statistical if not etiological associates of abnormal serum amylase levels. Because high amylase values so often occur in perforated ulcer, there is no amylase level that can be considered diagnostic of acute pancreatitis.

Amylases↗

p53 Protein overexpression in cholangiocarcinoma arising in primary sclerosing cholangitis.

The protein encoded by the p53 tumour suppressor gene plays an important part in the regulation of cell growth. Abnormalities of this gene represent one of the most common genetic changes in the development of human cancers. This study investigated the expression of p53 protein in cholangiocarcinoma arising in association with primary sclerosing cholangitis (PSC). Of the 14 patients with cholangiocarcinoma studied, 13 had underlying PSC. The expression of p53 protein was detected immunohistochemically in paraffin wax embedded liver specimens, after microwave pretreatment. The expression of p53 protein was shown in the cholangiocarcinoma tissue of 11 of 14 (78.5%) patients. In five of 10 patients, the accumulation of p53 protein highlighted the presence of neoplastic cells in biliary tissue separate from the main tumour. These cells were mainly located in the septal bile ducts or in the accessory glands, or both, but occasionally also in large portal areas at the periphery of nerves and lymphatics, and in one case in the mucosa of an extrahepatic bile duct. No p53 protein was detectable in liver tissue obtained at the time of transplantation in 15 patients with PSC but not cholangiocarcinoma. These results show that cholangiocarcinoma development in PSC is commonly associated with abnormalities of p53 and that these occur at a late stage in the development of the malignant process. Staining for p53 protein could represent an additional criterion for the diagnosis of cholangiocarcinoma development in patients with PSC.

Adult↗

Carcinoma of the skin with perineural invasion.

PURPOSE: To evaluate the outcome and patterns of relapse in patients treated for skin carcinoma of the head and neck with either microscopic or clinical perineural invasion. METHODS AND MATERIALS: Radiotherapy alone or combined with surgery was used to treat 135 patients with microscopic or clinical evidence of perineural invasion of skin carcinoma. All patients had at least 2 years of follow-up. RESULTS: The 5-year local control rates without salvage therapy were 87% with microscopic perineural invasion and 55% with clinical perineural invasion. Overall, 88% of the local failures occurred in patients with positive margins. Almost half of the recurrences in patients with microscopic perineural invasion were limited to the first-echelon regional nodes. However, only 1 of 11 patients with basal cell carcinoma with microscopic perineural invasion had a nodal failure. Ninety percent of recurrences in patients with clinical perineural invasion occurred at the primary site. Cranial nerve deficits rarely improved after successful treatment of the primary disease. Radiographic abnormalities remained stable 30% of the time when patients had clinical evidence of progressive disease. CONCLUSIONS: Radiotherapy in patients with skin cancer with clinical perineural invasion should include treatment of the first-echelon regional lymphatics. The risk of regional node involvement is also relatively high for patients with squamous cell carcinoma with microscopic perineural invasion. In patients with clinical perineural invasion, the poor local control rates with conventional radiotherapy suggest a need for dose escalation with or without concomitant chemotherapy.

Adult↗

Bone scintigraphy in testicular tumors.

PURPOSE: Testicular tumors do not occur frequently. Primary treatment is surgical, and radiotherapy and chemotherapy can play important roles in cases of metastatic disease. Bone scintigraphy is used largely for early detection of skeletal metastases from several tumors, and conventional radiographic studies are less sensitive than the nuclear technique for such a purpose. The aim of this study was to identify the role of bone scintigraphy in cases of testicular tumors, regardless of the grade. MATERIALS AND METHODS: The authors examined 28 patients (8 to 52 years old) with proved testicular tumors using Tc-99m MDP (750 MBq; 20 mCi) injected intravenously. Whole-body images were obtained 2 hours later, at 500,000 counts per image. Radiographic studies were obtained to investigate abnormal areas noted on scintigraphy. RESULTS: The results of bone scintigraphy were abnormal in seven cases, consisting of variable but diffuse uptake in the iliac bone on the same side as the affected testicle. MDP uptake was substantial in five of these patients (four seminomas, one nonseminoma; only two radiographic studies were abnormal), and the two other patients had moderate uptake of the radiopharmaceutical (two seminomas; radiographic studies were normal). Metastases were confirmed by biopsy in three cases. DISCUSSION: Early metastases from seminomas can occur through the lymphatic drainage toward the iliac lymph node chain. This could explain these findings. The scintigraphic aspects of the affected iliac bones seem characteristic. CONCLUSIONS: Early detection of metastases is very important to ensure the efficacy of radiotherapy and chemotherapy. Bone scintigraphy may play an important role in such cases and seems to be more sensitive than conventional radiography. Testicular tumor metastases should be considered when iliac involvement is observed. Paget's disease should be included in a differential diagnosis.

Adolescent↗