Brenner tumour of the ovary--an incidental histological finding.

Brenner tumours of the ovary are uncommon neoplasms and mostly benign. There is general agreement that Brenner tumors are derived from the surface epithelium of the ovary or the pelvic mesothelium through transitional cell metaplasia. It is essential to categorise these tumours as benign, borderline or malignant type as the biologic behaviour and choice of surgery differs in all of the three categories. The authors report a case of Brenner tumour that had only a single area with a beginning indistinct stroma vessel invasion. However the presence of characteristic epithelial nests, fibromatous stroma, and marked cytological metaplasia without atypia provided important clues to the correct diagnosis--proof of a benign tumour.

Presentation of a patient with in situ amelanotic melanoma of the vulva.

Amelanotic malignant melanoma of the vulva is extremely rare. The authors describe here a case of amelanotic malignant melanoma of the vulva, occurring in a 71-year-old woman without any clinical symptoms. The woman had a small nodular lesion in the left labia majora. Local excision was performed. Histological examination revealed an in situ malignant melanoma without any evidence of invasive disease. All suspicious lesions in the vulva region, even if there are no clinical symptoms, should be biopsied, and if an in-situ melanoma is identified, partial or total vulvectomy should be considered.

Coexpression of IL-6 and TNF-α: prognostic significance on breast cancer outcome.

Presented study was conducted to investigate the prognostic significance of the coexpression of serum interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in breast cancer, by correlating their presence with clinicopathological characteristics indicative of tumor progression and the overall survival of breast cancer patients. One hundred twelve consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of IL-6 and TNF-a were measured by quantitative sandwich enzyme immunoassay (ELISA). Median split was used to subdivide patients with low or high IL-6 and TNF-a levels. A positive association between the expression of the two cytokines was found. The coexpression of high IL-6 and TNF-α was independently associated with extended lymph node (>3) involvement (aOR, 7.8) and lymphovascular invasion (aOR, 14.1), increasing the prognostic significance of each cytokine separately; it also provided additional prognostic information regarding survival, defining a high-risk subgroup of patients with significantly shorter survival and higher risk of death compared to patients with both cytokines low (aHR, 4.45) and patients with only one cytokine high (aHR, 3.63). Our findings suggest that the coexpression of these two cytokines could be used clinically as a useful tumor marker for the extension and the outcome of the disease.

Avoiding appendectomy with an ultrasound probe.

Acute appendicitis is common in patients with right lower quadrant pain and affects all gender and age groups. Because clinical diagnosis of patients with right lower quadrant pain remains a challenge to emergency physicians and surgeons, imaging is of major importance. Ultrasound has well-established direct and indirect signs for diagnosing acute appendicitis and revealing the presence of an appendicolith. Appendectomy, which can be either open or laparoscopic, constitutes the basic treatment. However, the need for an appendectomy is debatable, particularly in high-risk patients. We report the case of a 42-year-old woman with no relevant medical history who was sent to the emergency department by her family physician with right lower quadrant pain of 18 hours' duration. Using ultrasound, the emergency physicians identified, inside the appendix, a 0.6cm appendiceal faecolith, migration of which was eventuated by manipulation of the ultrasound probe. The patient was then successfully treated non-operatively without any antibiotic prescription. Despite its rarity, migration of an appendiceal faecolith is possible. When migration of an appendicolith is perhaps actualised spontaneously or by ultrasound probe manipulation, the likelihood of an appendectomy decreases dramatically. This hypothesis provides patients who present an appendiceal faecolith with an alternative treatment approach that will lead to the avoidance of surgery, minimise morbidity and reduce hospitalisation costs.

Alterations in colonic transit time after laparoscopic versus open cholecystectomy: a clinical study.

PURPOSE: Postoperative enteral paresis constitutes a common problem for surgeons around the world. Evidence by many authors suggests that colonic inertia constitutes a major component of postoperative enteral paresis. This study aims at comparing the effect of laparoscopic versus open cholecystectomy on colonic transit time in humans. MATERIALS AND METHODS: In this study, were included a total of 29 patients suffering from cholelithiasis, divided into two groups, a laparoscopic cholecystectomy and an open cholecystectomy group. All patients ingested one capsule containing 24 radiopaque markers on the day of the operation, and plain abdominal films were obtained on the 3rd postoperative day. The number of remaining markers was counted, and the percentage of rejected markers was calculated. For the statistical analysis, SPSS for windows version 12 was used. RESULTS AND DISCUSSION: The study's results show a significant difference in postoperative colonic motility, in favor of the laparoscopic cholecystectomy group (P = 0,001). Causative interpretation of these results is difficult, mainly due to the multifactorial nature of postoperative colonic hypomotility. CONCLUSION: The present study suggests an advantage of laparoscopic cholecystectomy, as far as the duration of postoperative colonic paresis is concerned.

Colorectal carcinoma: correlation between age, gender and subsite distribution.

BACKGROUND: Several studies have shown a migration in the occurrence of colorectal cancer (CRC) toward a proximal colonic location. The aim of this study was to examine the interrelationship between the anatomical distribution of CRC and gender, age at presentation, and incidence rates for the disease in the inhabitants of Thrace, Northern Greece. METHODS: A retrospective study was conducted on CRC cases diagnosed in a northern part of Greece (Evros region, 150.000 inhabitants), in the First Department of Surgery of the University General Hospital of Thrace, between 1982 and 1997. Two time periods were compared (1982-1989 and 1990-1997), at which age at diagnosis (28-88 years), gender, the incidence and subsite location of CRC were identified in the patients. Tumors were classified into right-sided cancers (from the cecum to and including the splenic flexure), left-sided cancers (located in the descending and the sigmoid colon), and rectal cancers (rectal lesions). The chi-square test and Fischer's exact test were used to compare the data. RESULTS: During the entire study period (1982-1997), 143 cases of CRC were identified in our department. This cohort comprised 71 males and 72 females, with mean ages of 66 years and 64.7 years, respectively. The population remained almost stable during this time period. The incidence of CRC was significantly higher in the latter part of the study (1990-1997 compared to 1982-1989) for both genders (p < 0.001), with this increase being higher among the female patients with CRC (by 17.32%, p = 0.474). The analysis also revealed that the disease occurred at a significantly higher frequency at a later age (p = 0.002), especially in patients with RC (p = 0.001). A proximal migration of CRC was observed in the latter part of the study (p = 0.495), with the frequency of right-sided cancers increasing significantly among the females (by 119%, p = 0.025). CONCLUSIONS: The incidence of CRC has increased in our region. In addition, a proximal migration of tumors over time was identified, especially in older and female individuals, which was linked to a decrease in the incidence of left colon cancer. These findings have important implications for the choice of CRC screening strategies.

Increased B7H4 tissue expression correlates with high CA19.9 serum levels and a worse prognosis of pancreatic adenocarcinoma.

Pancreatic cancer (PC) is a leading cause of cancer death worldwide, especially in Western societies. Its aggressive nature and poor prognosis increase the need for identifying new and more accurate diagnostic and prognostic tools. We studied 41 patients who had undergone radical surgical resection for PC, investigated B7H4 protein expression in the PC tissue specimens of these patients by immunohistochemistry and analyzed several clinical and pathological features. The positive expression of the B7H4 antigen was associated with a negative impact of chemotherapy with gemcitabine on patient survival and also correlated with high CA19.9 serum levels and poorly differentiated tumors. Moreover, patients that overexpressed B7H4 antigen had worse prognosis compared to the ones that did not overexpress B7H4. B7H4 antigen is a negative prognostic marker for PC patients and also seems to express resistance of PC patients to chemotherapy with gemcitabine.

Proliferative breast disease: epidemiologic aspects, and cytologic diagnosis.

PURPOSE: The aim of the present study is to describe the prevalence of proliferative breast lesions in cases of benign and malignant tumors of the breast as well as to assess the contribution of rapid intraoperative imprint cytology in the diagnosis of proliferative breast disease. METHODS: Frozen section and intraoperative imprint cytology were performed on breast tissue biopsies from 486 breast cancer patients who underwent primary surgical treatment. Imprints were stained either by the Papanicolaou (Pap) or the May Grünwald-Giemsa (MGG) or the Hematoxylin eosin (HE) technique. Cytologic diagnoses were compared to the histopathologic ones from paraffin sections. RESULTS: Sclerosing adenosis was the most common finding in benign breast biopsies while in breast cancer the prevalence of the lesion was reduced by half. On the other hand, atypical hyperplasias in malignant biopsies were almost twice as many as in benign ones. Imprint cytology presented high sensitivity and specificity (99% and 96% respectively) in distinguishing benign proliferative from malignant lesions as a whole, but regarding atypical hyperplasias the specificity was significantly reduced (76% vs 96%). CONCLUSION: Clarification of cytologic diagnostic criteria and expertise in cytologic interpretation could show off intraoperative imprint cytology as a useful and inexpensive diagnostic tool providing the surgeon with prompt and accurate information regarding the nature of breast lesions.

K statistic as a measure of quality control in cervicovaginal cytology.

Quality assessment schemes are widespread in most branches of pathology but are uncommon in the more subjective areas of histopathology and cytology. Researchers in many fields have become increasingly aware of the observer as an important source of measurement error. The validity of any method of reporting evidence of an abnormal process in cellular material is based on the degree of correlation with the actual disease process as it exists in the tissue and its reproducibility. Correlations can be tested in retrospective studies in which diagnoses based on cellular evidence are matched against the disease process present in biopsy specimens. Correlations can also be tested by examination of a set of unknown cellular preparations obtained in the presence of proven disease. While reproducibility is indirectly related to correlation, it is meant to imply satisfactory utilization of the method by other groups of cytotechnologists and cytopathologists. While cytopathology will continue to play an important role as a screening technique for the detection of cancer of the uterine cervix, its usefulness in the study of the early manifestations of the disease process is yet to be realized on a universal basis.

Spontaneous abortions with increased CD5 positive cells in the placental tissue during the first trimester of gestation.

Most spontaneous abortions occur before 12 weeks' gestation, and most are due to chromosomal errors in the conceptus. Relatively few truly spontaneous abortions take place between 12 and 20 weeks' gestation. Thereafter, between 20 and 30 weeks another type of premature spontaneous termination due to ascending infection becomes prevalent. The number of cells expressing the various lymphocytic markers changes throughout pregnancy. In the present study, we investigated the immunohistochemical expression of mononuclear infiltrations in paraffin-embedded placentas, from fetuses after spontaneous abortion (8th, 10th, and 12th week of gestational age), and those after therapeutic abortion at the same time, using a panel of monoclonal antibodies for the identification of leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26), T-lymphocytes (CD45RO/UCHL1) and CD5 cells. Immunologic factors in human reproductive failure are plausible mechanisms of infertility and spontaneous abortion. Approximately 25% of cases of premature ovarian failure appear to result from an autoimmune etiology. Unfortunately, current therapeutic options for these women are limited to exogenous hormone or gamete substitution. Local inflammation at the sites of endometriosis implants are postulated to mediate the pain and reduce fecundability associated with this clinical syndrome. The recruitment of immune cells, particularly monocytes and T cells, neovascularization around foci of invading peritoneal lesions, and the possible development of antiendometrial autoantibodies support an immunologic basis of this disorder. To date, treatment of pain and infertility associated with endometriosis is primarily surgical, although immune-based adjuvants are theoretical possibilities for the future. Finally, although hypotheses supporting immunologic mechanisms of recurrent pregnancy loss have been popular over the past decade, most clinical investigations in this area do not provide compelling evidence for this position. Reputable specialists in reproductive medicine use experimental immunotherapies judiciously in selected cases of repetitive abortion. For example, the use of anticoagulation therapy can be beneficial in cases with documented antiphospholipid antibodies. At present, however, efficacious immunotherapy protocols for general application have not been established. Despite these caveats, continued strides in our understanding of human reproductive immunology, should yield considerable future progress in this field. We conclude that, 1) maternal cells, probably CD45RO/UCHL1 positive cells, cross the maternofetal barrier and participate in spontaneous (involuntary) abortions, 2) a small proportion of maternal cells (approximately 30%), probably CD5 positive cells, also cross the maternal fetal barrier and cause growth delay and recurrent reproductive failure. The results were statistically significant (p < 0.0001, Student's t-test).

Expression of fibrillar proteins and vimentin in developing chorionic villi is related to fetal maturation.

Using an immunocytochemical technique, the extracellular matrix components fibronectin, vimentin, laminin and collagen type IV were investigated in human chorionic villi of various stages of development. Fibronectin and laminin were consistently positive throughout embryonic development. Vimentin and collagen type IV were negative in first and second trimester chorionic villi, but became positive in term placentas. With the exception of laminin, all extracellular matrix molecules were detected in the villous stroma and, with the exception of vimentin, they were localized in the basement membranes. Our data suggest that fibronectin and laminin are essential components of the villous structure, while the presence of vimentin and collagen type IV in the chorionic villi should be regarded as an indicator of fetal maturation.

Expression of laminin, type IV collagen and fibronectin molecules is related to embryonal skin and epidermal appendage morphogenesis.

Basement membrane zones are specialized sheets--like arrangements of extracellular matrix proteins and glycosaminoglycans, and act as an interface between parenchymal cells and support tissue. They separate epithelium, endothelium, muscle cells and Schwann cells from adjacent connective tissue stroma, and also from a limiting membrane in the central nervous system. They are involved in several cellular and biological processes, including adhesion, migration and cellular differentiation. Basement membranes have five major components: collagen type IV, laminin, heparan sulfate, entactin, and fibronectin. In addition, there are numerous minor and poorly characterized protein and glycosaminoglycan components. The various components of the basement membranes of the skin (collagen type IV, proteoglycans--heparan sulfate, laminin, entactin and fibronectin) are products of the epithelial (epidermal) cells. We studied immunohistochemically the origin, the first appearance and distribution of the adhesive extracellular glycoprotein laminin and the fibrillar proteins of the extracellular matrix collagen type IV and fibronectin in the basement membranes of fetal human skin between 12 to 21 weeks of gestational age. Additionally, we studied the expression of vimentin in the extracellular matrix of the epithelial/mesenchyme junction of the skin. This study demonstrates clearly that the expression of the antigens laminin, collagen type IV and fibronectin starts in the germinative epithelial cells of the skin at the bulbs of the hair follicles (12th week for fibronectin and 19th week for laminin and collagen type IV), and migrating progressively involves the epithelial epidermal cells of the covering skin, as well as, the basement membrane at the dermal-epidermal junction in that region (between 20 to 21 weeks of gestational age).

γ -H2AX: A Novel Prognostic Marker in a Prognosis Prediction Model of Patients with Early Operable Non-Small Cell Lung Cancer.

Cancer is a leading cause of death worldwide and the prognostic evaluation of cancer patients is of great importance in medical care. The use of artificial neural networks in prediction problems is well established in human medical literature. The aim of the current study was to assess the prognostic value of a series of clinical and molecular variables with the addition of γ -H2AX-a new DNA damage response marker-for the prediction of prognosis in patients with early operable non-small cell lung cancer by comparing the γ -H2AX-based artificial network prediction model with the corresponding LR one. Two prognostic models of 96 patients with 27 input variables were constructed by using the parameter-increasing method in order to compare the predictive accuracy of neural network and logistic regression models. The quality of the models was evaluated by an independent validation data set of 11 patients. Neural networks outperformed logistic regression in predicting the patient's outcome according to the experimental results. To assess the importance of the two factors p53 and γ -H2AX, models without these two variables were also constructed. JR and accuracy of these models were lower than those of the models using all input variables, suggesting that these biological markers are very important for optimal performance of the models. This study indicates that neural networks may represent a potentially more useful decision support tool than conventional statistical methods for predicting the outcome of patients with non-small cell lung cancer and that some molecular markers, such as γ -H2AX, enhance their predictive ability.

A dose escalation study of pegylated liposomal Doxorubicin (caelyx) in combination with capecitabine (xeloda) in patients with refractory solid tumors.

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) and capecitabine (CAP) have separately shown significant antitumor activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. PATIENTS AND METHODS: Fifteen patients with histologically confirmed inoperable solid neoplasms were enrolled. The patients' median age was 65 years, 10 were male, and 12 had a performance status score (WHO) of 0-1. PLD was administered on day 1 as a 1-hour intravenous infusion at escalated doses ranging from 35 to 40 mg/m(2). CAP was administered on days 1-14 per os, at escalated doses ranging from 1,600 to 1,800 mg/m(2), given as two daily divided doses. Treatment was repeated every 3 weeks. RESULTS: At the dose of PLD 40 mg/m(2) and CAP 1,800 mg/m(2), all 3 enrolled patients presented DLTs [2 patients grade 3 palmar-plantar erythrodysesthesia (PPE) and 1 patient grade 3 asthenia] and thus, the recommended MTD for future phase II studies is PLD 40 mg/m(2) and CAP 1,700 mg/m(2). A total of 57 treatment cycles were administered. Grade 2/3 neutropenia complicated 9 (17%) cycles and 1 patient was hospitalized for febrile neutropenia. There was no septic death. The main nonhematologic toxicity was PPE grade 2 in 3 (19%) patients and grade 3 in 4 (27%). PPE was the reason of treatment interruption for 3 patients. Other toxicities were mild and easily manageable. Two patients (16%) with partial response suffering from gastric cancer and 5 patients with (42%) stable disease were observed among 12 evaluable patients. CONCLUSIONS: The results of this phase I study demonstrate that PLD and CAP can be combined at clinically effective and relevant doses. However, PPE is a common side effect and further investigation is warranted to define its precise role in the treatment of solid malignancies.

Concurrent administration of Docetaxel and Stealth liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection.

The substantial augmentation of the radiation sequelae during chemo-radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo-radiotherapy scheme with Stealth liposomal doxorubicin (Caelyx and Docetaxel (Taxotere in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere was 20 mg m(-2) week and of Caelyx was 15 mg m(-2) every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere/Caelyx was, thereafter, increased to 20/25 (five patients) and 30/25 mg m(-2) (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The 'in-field' radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere/Caelyx chemo-radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the 'in-field' toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer.

Emergency operations for carcinoma of the colon.

The aim of this retrospective clinical study was to record and analyse the immediate and long term results obtained from emergency operation for carcinoma of the large bowel. In a 12-year period (1991-2003), 154 patients were operated on for carcinoma of the colon. In 29 patients (19%; 11 males, 18 females, m.a. 72.8 years and 67.5 years respectively), the operation was performed urgently. In 21 (72.5%) there was a complete obstruction located in 17 (81%) at the sigmoid, in 2 (9.5%) in right flexure and in 2 (9.5%) in left flexure. Five patients (17%) had developed peritonitis due to perforation proximal to the tumour and three patients (10.5%) had developed necrotic colitis and haemorrhage due to the obstruction. In 23 patients (79.5%) a radical curative operation was feasible [11 (38%) subtotal colectomies with ileo-rectal anastomosis, seven (24%) Hartman's, three (10%) right hemicolectomy and two (7%) on table bowel lavage plus colectomy with ileo-rectal anastomosis] and in six (11%) only palliative operations could be done (transverse loop colostomy). In all cases the postoperative period was uneventful. Three patients with palliative operation were submitted to a radical curative operation 2 months later and the other three patients died 6 months later from causes irrelevant to the primary disease. It is concluded that in this series of patients radical curative operations for carcinoma of the large bowel even under urgent conditions were feasible in the cases without additional complications, eliminating the necessity for reoperations later on.

The contribution of rapid intraoperative cytology to the improvement of ovarian cancer staging.

OBJECTIVE: The goal of this work was to evaluate the use of intraoperative cytology in the improvement of ovarian cancer staging. METHODS: Fifty-two patients with clinical stage IA-IIB ovarian cancer underwent peritoneal washing (PW) cytology and imprint cytology performed on retroperitoneal lymph node samples, during primary surgical treatment. Cytologic specimens were stained by the May-Grünwald-Giemsa (MGG) and hematoxylin-eosin (HE) techniques. Pertinent histologic sections of the ovarian lesions, cell blocks prepared from PW sediments, and lymph node samples were studied and compared with the cytologic findings. RESULTS: Our study reveals that, when malignant cells are present in the peritoneal cavity, PW cytology has 84.6% sensitivity and 94.7% specificity in detecting them. Imprint cytology performed on lymph node samples presented 94.1% sensitivity and 94.1% specificity in the diagnosis of retroperitoneal metastasis of ovarian cancer. Only 7 patients (13.4%) were upstaged with either cytologic method. PW cytology alone upstaged 6 more patients, while imprint cytology alone upstaged 11 more patients. This corresponds to a total of 17 patients (32.6%) who benefit from the combined performance of both cytologic methods. HE stain presents lower values of sensitivity and specificity compared with MGG. CONCLUSION: Cytologic evaluation of intraperitoneal and retroperitoneal spread of ovarian cancer by use of PW cytology and imprint cytology performed on lymph node samples contributes to the improvement of ovarian cancer staging.