5 to 8 years follow-up of knee chondral defects treated by PVA-H hydrogel implants.

AIM: Despite the various treatment options available, symptomatic articular cartilage defects continue to represent a therapeutic challenge for knee surgeons. This study has been developed in order to retrospectively evaluate and present long term results, from 5 to 8 years, of PVA-H hydrogel impants ("Cartiva") in the treatment of knee chondral focal defects. PATIENTS AND METHODS: Presented are the clinical and MRI evaluation of 18 patients with III and IV degree knee chondral or osteochodral defects treated by PVA-H hydrogel implants. Defects were no larger than 20 mm in diameter. Average age at time of surgery was 54 years. There were 11 male and 7 female patients. A total of 20 implants were implanted, 16 with 10 mm and 4 with 15 mm Cartiva implants. One patient was treated bilaterally. The majority (80%) of surgeries were performed arthroscopically. Patients have been assessed by IKDC, SF36 scores and by MRI imaging. RESULTS: All patients have shown improvement of knee function and knee scores, in many cases over 50 points of IKDC, except three. Of these, the first mantained a rather good quality of life for over 5 years with approximately the same level of functionality she enjoys now, after implant removal and knee replacement during 2008. The second case was a 43 year old female with a post-traumatic chondral defect in a valgus knee. The patient experienced post-op pain: the implant was removed among another institution at 6 months post-op and was converted to OATS. The third case was a 49 year old male with a severe arthritic pre-op knee and may not have been ideal candidate for Cartiva, but was too young for a total knee replacement at the time of operation and, despite a severe knee worsening during the last year that will need in the short future a knee replacement, has, at over 6 years follow-up, an IKDC score of 33.33 from a pre-op of 37.93. CONCLUSIONS: 5 to 8 yy follow-ups enable us to conclude that the use of PVA-H synthetic implants in knee chondral defects in middle aged patients can guarantee critical knee function improvement and severe pain reduction. Even the patients, that have needed a knee replacement, have well done for the first four-five years. Therefore, this mean that this type of treatment with the correct indications and future implant and instrumentation improvements, already in course, may guarantee a several year period of knee health and active life style.

Dynamics of the global tyrosine phosphorylation during capacitation and acquisition of the ability to fuse with oocytes in human spermatozoa.

Phosphorylation of tyrosine residues in cellular proteins represents a major event during sperm capacitaton, but its relationship with the acquisition of sperm-fertilizing ability is still unclear. In this study we explored the relationship between the kinetics of the global tyrosine phosphorylation, monitored with a flow cytometric assay, and the acquisition of the human sperm ability to fuse with oocytes, evaluated with the progesterone-enhanced hamster egg penetration test. Sperm tyrosine phosphorylation appeared to be an early event in the capacitation process, with a 3.6-fold mean increase within 1 h of capacitation, but at this time sperm-oocyte fusion was extremely poor compared with that observed at 5 h of capacitation. Capacitation in calcium-free medium produced a 2-fold mean increase in tyrosine phosphorylation compared with that seen in complete capacitation medium both at 1 h and 5 h of capacitation, whereas sperm-oocyte fusion significantly increased only at 1 h, remaining unchanged at 5 h of capacitation. The cAMP analog, N,2-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP), prevented the inhibitory effect of seminal plasma on tyrosine phosphorylation but not on sperm-oocyte fusion. In conclusion, these results suggest that the acquisition of sperm-fertilizing ability is always associated with an increase of the global tyrosine phosphorylation, but tyrosine phosphorylation does not necessarily reflect the acquisition of the sperm-fertilizing ability. Flow cytometry assay, a reliable technique to quickly quantify the global levels of the human sperm tyrosine phosphorylation, could be useful for a further elucidation of the biological meaning of this process, with the perspective of its clinical use as a measure of the sperm-fertilizing potential.

The inhibition of the human sperm phosphatidylinosytol 3-kinase by LY294002 does not interfere with sperm/oocyte interaction.

It has recently been reported that the selective inhibition of phosphatidylinosytol 3-kinase (PI3K) enhances human sperm motility. However, little information exists on a possible role of PI3K in other sperm functions involved in the fertilization process. In this study, we investigated whether LY294002 could affect human sperm ability to fuse with oocytes, by means of the hamster egg penetration test (HEPT). The effect on acrosome reactions (AR) and on sperm/zona pellucida (ZP) binding was also evaluated. The pre-incubation with scalar doses of LY294002 (0.1, 1 and 10 microm) did not interfere with sperm ability to fuse with oocytes either in the conventional version of the HEPT or in the version enhanced with progesterone (P). No interference with the stimulatory effect on AR exerted by P or mannose-bovine serum albumin (mannose-BSA) was revealed. Finally, LY294002 had no effect on sperm/ZP binding. These results indicate that the inhibition of PI3K by LY294002 does not interfere with sperm interaction with oocytes. This is noteworthy in the view of a possible clinical use of LY294002 as an in vitro stimulator of the sperm motility of asthenozoospermic patients for assisted reproduction techniques.

A long-standing cystic lymph-node metastasis from occult thyroid carcinoma.

Here we report the case of a patient with a soft tissue mass of the neck. For more than 10 years it was thought to be a branchial cyst and was later diagnosed to be a cystic lymph node metastasis from an occult thyroid carcinoma.

Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers.

The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on approximately 95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only approximately 50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR for CEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 < 0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and/or disease monitoring.

[Unusual case of kidney rupture]. / Un raro caso di rottura di rene.

The Authors report a case of renal rupture in a patient 36 years with acute abdominal pain and progressive anaemia. The history of the patient shows no past signs and symptoms of either renal pathology or traumatic event. Radiological examinations demonstrates dislocation of the kidney through presence of large retroperitoneal formation interpretable as haematoma. Progressing bloodless, they proceeded to embolization of renal artery and successive nephrectomy. Only histological examination of the removed kidney demonstrates the presence of a renal clear cells adenocarcinoma.

Incidence of chromosomes 1 and 17 aneusomy in breast cancer and adjacent tissue: an interphase cytogenetic study.

BACKGROUND: Characterization of the biopathologic events underlying the early steps of breast carcinogenesis may have a dramatic impact on reducing breast cancer mortality. Genes involved in breast tumorigenesis are localized on chromosomes 1 and 17, and numeric aberrations of these chromosomes have been correlated with breast cancer tumorigenesis and progression. According to the field cancerization hypothesis, specific chromosome aberrations may be present in breast cancer and in normal-appearing adjacent tissue. The latter changes reflect the genomic damage that follows longterm carcinogenic exposure and precede the morphologically detectable neoplastic transformation. We hypothesize that detection of these aberrations in benign breast epithelium may provide a tool for molecular risk assessment. STUDY DESIGN: Using fluorescence in situ hybridization with centromere-specific probes, we determined the status of chromosomes 1 and 17 in fresh imprints of 28 samples of primary tumors and 54 samples of their surrounding uninvolved parenchyma taken from patients undergoing operations for breast carcinoma. Ten contralateral breast biopsy specimens collected from patients with previous breast carcinoma were also evaluated as a surrogate of a high-risk group to rule out the hypothesis that chromosomal aneusomy in tumor-adjacent tissue could be related to a paracrine effect of the primary tumor. Ten samples of benign breast tissue taken from patients at low risk were used as controls to define tolerance limits for aneusomy definition. RESULTS: Using threshold values of 40% of signal loss and 13% of signal gain to define chromosome aneusomy (ie, mean + 3 SDs of the control group signals), we found the following: 1) almost all primary breast tumors were aneusomic for chromosomes 1 and 17; 2) primary breast tumor and adjacent uninvolved parenchyma shared the same pattern of chromosomes 1 and 17 aneusomy in 66.7% of patients; and 3) chromosomes 1 and 17 aneusomies in contralateral benign breast samples from high-risk patients were not different from those in primary breast tumor or adjacent tissue samples. CONCLUSIONS: These results suggest that chromosomes 1 and 17 aneusomy may represent an intermediate biomarker of breast tumorigenesis potentially useful to detect patients at high risk of breast carcinoma who may benefit from preventive interventions.

Bilateral symptomatic adrenal myelolipoma.

Myelolipomas of the adrenal gland were first described in 1905. They are rare cortical, nonfunctioning, benign neoplasms, generally unilateral, usually discovered by accident or at autopsy. Thus they are often classified as 'incidentaloma'. These tumors are more frequent in males 40-60 years old. Most adrenal myelolipomas are small (diameter < 4 cm) and asymptomatic (70%), but larger tumors may cause local symptoms secondary to mechanical compression. Very large bilateral adrenal myelolipomas are exceedingly rare. They generally require no treatment; however, if symptomatics or if diagnosis is in doubt, surgery is needed. Usually only monolateral adrenalectomy is performed, even in the presence of bilateral tumors, to preserve adrenal function. We present a case of bilateral, symptomatic giant myelolipoma in a young woman, treated with bilateral adrenalectomy.

Vulvar squamous carcinoma: prognostic role of DNA content.

DNA nuclear content was evaluated on 46 paraffin-embedded blocks of vulvar cancer by means of flow cytometry. Fifteen of 44 evaluable samples (34%) were found to have an aneuploid DNA pattern. Aneuplody showed a statistically significant relationship with tumor grading (P = 0.0004) and defined a subset of patients who have pathological characteristics of high risk, such as advanced stage of disease, deepest stromal invasion, or positive inguinal nodes. However, when a multivariate regression model was used, ploidy status did not have any prognostic role, while FIGO staging system was confirmed to be the strongest independent prognostic factor (P = 0.009). The integration of a panel of cell kinetic parameters with traditional features is worth investigating on a larger population.

[The anterior commissure of the larynx in the subperichondral functional surgery of the glottic plane: critical evaluation on the basis of a serial section study in normal and neoplastic laryngeal specimens]. / La commissura anteriore della laringe nella chirurgia funzionale sottopericondrale del piano glottico: considerazioni critiche sulla base di uno studio istologico seriato in laringi normali e neoplastiche.

It is a well-known fact that the clinical growth of laryngeal cancer varies according to the site of its origin. A number of macro and microscopy studies have attempted to explain the various routes it follows in spreading. The anatomical features of the anterior commissure, the conus elasticus and posterior commissure condition the direction and extent of tumour spreading as do the blood supply in the glottis and the distribution of mucous glands in the glottis and subglottis. Of the various regions of the larynx, the anterior commissure has provided perhaps the greatest challenge to investigators in that its boundaries as well as its morphology are still not clear. The possible spreading of glottic cancers exceeding these anatomic structures is very difficult to evaluate using two dimensional picture given by laryngoscopy as well as the images provided by TC and NMR which justifies a different behavior of same stage. Therefore these elements, in addition to the absence of a universally accepted clinical definition of the boundaries of AC, justify the diagnostic, pathologic, and therapeutic problems linked to AC carcinoma. Eight normal adult larynges were studied by microdissection and serial section after fixation in 10 percent formalin followed by decalcification. These specimens were dissected according to the stages of "evisceratio laryngis" performed in our Department for the treatment of T1a, T1b tumors. Our observations confirm that the island located at the anterior insertion of the thyroarytenoid muscle, easy reached during subperichondral dissection, cannot be identified with the so-called tendon described by Broyles. The specimens shown circumstantiate the fact that this fibrous-cartilagineous island act as a barrier and that when the neoplasia does start to spread into this segment, this fibrous area forces it to spread mainly along the surface. Our observations were confirmed by histologic examination of 6 surgical specimens after "evisceratio laryngis" performed on T1a, T1b tumors. Clinical positive results in subjects treated employing "evisceratio laryngis" appear to further confirm of our interpretation to these morphological observations.

Spontaneous canine mammary tumors. A model for monoclonal antibody diagnosis and treatment of human breast cancer.

BACKGROUND: The increasing availability of monoclonal antibodies to human breast tumor-associated antigens offers a new means to evaluate whether antigenic similarities exist between human and animal breast tumors. The study of the biology of spontaneous mammary tumors in the dog, one of the most frequent neoplasias in this domestic animal, may be of interest in providing an experimental model for the clinical management of human breast cancer. EXPERIMENTAL DESIGN: In order to assess whether antigenic similarities do occur between human and canine breast cancer, in the present study we have evaluated the immunohistochemical reactivity of two normal mammary glands and 62 benign and malignant canine breast tumors with a panel of six MoAbs, (HMFG2, MBr1, B72.3, B6.2, X-10, B1.1) recognizing distinct human breast tumor-associated antigens. RESULTS: The results of the present study indicate that mammary neoplasias in dogs display an antigenic phenotype comparable to that observed in female and male human breast lesions. As has already been demonstrated in humans, only three among the six monoclonal antibodies tested (B72.3, B6.2, and X-10) appear to discriminate benign from malignant canine mammary tumors. CONCLUSIONS: These findings demonstrate that (a) this veterinary tumor may represent a suitable model for imaging and immunotherapy studies of human breast carcinoma and (b) the triplet of reagents capable of distinguishing selectively transformed glandular epithelium may be useful in the immunocytochemical presurgical diagnosis of these canine neoplasias.

Biologic and clinical correlations among ploidy, cell kinetics, and the tumor-associated glycoprotein-72 tissue expression in colorectal cancer. Preliminary findings.

PURPOSE: The aim of this study was to evaluate the possibility of identifying biologically aggressive subgroups of patients, combining several biologic parameters such as the tumor and normal mucosa values from the ploidy, the S-phase cell percentage, and tumor-associated glycoprotein-72 (TAG-72) expression. METHODS: One hundred five colorectal cancer patients were studied to analyze the possible prognostic role of ploidy and cell kinetics in multiple fresh specimens from the tumor and normal mucosa. Since the presence of TAG-72 in the colonic mucosa has been correlated to neoplastic transformation, the correlations between these parameters and the quantitative tissue expression of the TAG-72 were analyzed in a subgroup of 53 cases. RESULTS: A significantly lower five-year disease-free survival rate (21.4 percent) was observed in patients with multiploid tumors, when compared with that observed in patients with diploid or single aneuploid tumors (67.5 percent) (P = 0.03). The quantitative tissue TAG-72 expression contributed in identifying a particular patient subgroup (20 percent), characterized by S-phase percentage and TAG-72 values from the normal mucosa that were unexpectedly higher than 12.1 percent and 7.5 U/mg of proteins, respectively. In particular, when the 25 Dukes B patients were analyzed, similar results were observed. In fact, 14 (56 percent) cases showed high tumor cell proliferation and, surprisingly, a high tissue TAG-72 content in the normal mucosa was found in 4 (28.6 percent) of these patients. CONCLUSIONS: Other than multiploidy, the biologic aggressiveness of colorectal cancer might be successfully assessed introducing the evaluation of new biologic parameters, such as the TAG-72 content and S-phase percentage values of the normal mucosa, suggesting the possibility of further stratifying this patient population.

The transdural extension of gliomas.

The extraneural spreading of gliomas is an infrequent occurrence which is not necessarily related to either tumor histology or site. This paper reports two cases, a glioblastoma and an oligodendroglioma, both presenting extradural diffusion. In the first case, where there was severe intracranial hypertension, the tumor found its way out from the neurocranium, far from the site of the operation, perforating the dura and the bone of the cranial base. In the second case, the operation may have facilitated the extraneural invasion. This unusual behaviour of glial tumors is probably less rare than presumed. It may go unnoticed if the attention is concentrated on the usually severe neurological syndrome which is present in these patients.

[The recurrent multifocal pleomorphic adenoma]. / Le recidive multifocali di adenoma pleomorfo.

Pleomorphic adenoma (P.A.), the most common tumor of the salivary gland, demonstrates a peculiar clinicopathological behaviour for numerous reasons: the high recurrence rate following primary surgery (up to 50%), the appearance of malignancy (2-9%), the reported number of distant metastases histologically identical to the primary P.A. From among 71 cases of benign parotid tumors treated from Nov. 89 to Nov. 92 in the ENT Department of "Regina Elena", the National Cancer Institute in Rome, six particular cases showed multiple force of P.A. recurring after primary surgery performed from 3 to 32 years previously and are object of discussion in this study. All of these six cases had multiple recurrences, usually manifest as nodular clusters in the parotid area, while in three cases appeared as well a recurrence in the soft tissue of the neck, far removed from the parotid space, with no involvement of neck nodes as was revealed through histological examination following neck dissection. A hypothetical mechanism of diffusion is discussed. The Authors agree with the opinion which holds the surgeon's inability to successfully eradicate primary tumors responsible for the high frequency of recurrences. The surgical technique of "enucleation" is, in fact, inadequate in P.A. excision owing the high risk of mishandling or rupturing the tumor capsule with a consequent seeding of the tumor onto the surgical bed. Lateral lobectomy, with identification of the facial nerve, or total conservative parotidectomy (for deep lobe adenoma) are correct techniques in treating primary P.A.. The Authors also discuss management of recurrent P.A. in relation to facial nerve involvement. Preservation of the seventh nerve with eventual post-operative radiation should be considered an alternative to nerve sacrifice in selected cases of recurrent pleomorphic adenoma.

The association of Helicobacter pylori infection with low levels of urea and pH in the gastric juices.

Fifty-four gastric biopsies and their relative gastric juices were analyzed for the presence of Helicobacter pylori with both cultural and microscopic methods. Thirty-one samples were positive and twenty-three were negative. These data were therefore employed as references for the subsequent comparisons. Furthermore, the gastric juices were later tested to establish the urea concentration and the pH level. In addition, the sediment obtained after centrifugation was microscopically observed for the possible presence of other bacterial flora in the sample (unstained smears). The urease test on the bioptic specimens has also been evaluated. The presence of H pylori was strictly related to urea levels of less than 15 mg/dl and pH less than 3.5. Furthermore, H pylori was generally not associated with the presence of other bacterial flora (only 1 out of 12 samples). The latter instead, was almost exclusively present in high pH samples (with the exception of one). On the basis of these results, a simple diagnostic scheme was constructed to identify carrier subjects. All patients (14/14) with urea levels of more than 15 mg/dl were found to be negative as well as those presenting a pH of more than 3.5 (7/9) or evidence of other bacteria in the juices (8/9). The remaining subjects (30/31 or 29/31, respectively) presented H pylori in the gastric juices. The final classification was 96.3% (or 94.4%) correct.

Basophil-bound and serum immunoglobulin E directed against Helicobacter pylori in patients with chronic gastritis.

The immunoglobulin (Ig) E immune response in patients with Helicobacter pylori-associated chronic gastritis has been evaluated. Of 26 patients with H. pylori infection, 22 (84%) tested positive for basophil-bound specific IgE (determined by the histamine release test) and 18 (69%) for serum specific IgE (determined by an enzyme-linked immunosorbent assay). In contrast, only 1 of 17 persons in whom the bacterium was not detected presented cell-bound and serum specific IgE. In the 4 histamine release test--positive but enzyme-linked immunosorbent assay--negative patients, removal of antibody from the basophil surface by acid elution showed that histamine release occurred through an IgE-dependent mechanism. When normal basophils, passively sensitized with serum from IgE-positive patients, were exposed to the H. pylori antigen, a significant release was observed, confirming the class specificity of the response. Inhibition experiments with bacteria other than H. pylori showed that the IgE antibody was specifically directed against this organism. The percentage of antigen-induced histamine release did not correlate with serum specific IgE level. However, the response of basophils to antigenic challenge was proportional to IgE-dependent cellular releasability. This finding suggests that target cell sensitivity may be the most important factor in determining the entity of biological response to the antigenic challenge. The ability of H. pylori to induce a specific IgE immune response could answer key questions regarding the mechanisms inducing gastric inflammation.

[Hip prosthesis: idea, indications, development]. / Le artroprotesi dell'anca. L'idea, le indicazioni, l'evoluzione.

The authors describe the evolution and the successive stages that were necessary until the present total substitution of the hip joint could be worked out. The earliest attempts were made in 1923, but only in 1953, professor Marino Zuco, of Rome University Orthopedic Department started to carry out operations of arthroplasty, after 3 years of experimental research. In 1960, Charnley introduced the use of cement (methyl methacrylate), thus initiating the practice of total hip substitution. This surgery is indicated in a variety of joint pathologies of which osteoarthritis is the most frequent one. The implant of a cemented or non cemented prosthesis is conditioned both by the patient's age and by bone structure. Differences between the two types of prostheses are illustrated as well as the causes of failure or subsequent pathology and their diagnosis.

[Carcinoma of the endometrium in young women]. / II carcinoma dell'endometrio nella donna giovane.

Eighteen cases of endometrial cancer under 45 years were clinically and pathologically reviewed. Epidemiological analysis confirmed obesity as an effective risk factor for this neoplasia. In only three cases the association of adenomatous hyperplasia with endometrial cancer was discovered. These data support the theory that in young women endometrial cancer is not an endocrine related neoplasia.