Bernt Boeryd

Ovarian endometrioid carcinomas simulating sex cord-stromal tumors : A study using inhibin and cytokeratin 7

SummaryWe have investigated the use of inhibin and cytokeratin-7 (CK-7) in distinguishing endometrioid ovarian carcinomas (both typical and sex cord-like) from granulosa cell and Sertoli cell-containing ovarian tumors. Immunohistochemical staining with inhibin, CK-7. and epithelial membrane antigen (EMA) was performed on 6 endometrioid carcinomas simulating sex cord-stromal tumors, 5 typical endometrioid carcinomas, 14 adult granulosa cell tumors (AGCTs), 3 Sertoli-Leydig cell tumors (SCLTs), and I sex cord tumor with annular tubules (SCTAT). All AGCTs and SLCTs as well as the SCTAT were inhibin-positive. In contrast, all of the endometrioid carcinomas (both typical and those mimicking sex cord-stromal tumors) were inhibin-negative. CK-7 expression was not observed in the granulosa cell tumors and it was noted only in retiform areas in SLCTs. All 5 typical endometrioid carcinomas and 5 of the 6 sex cord-like endometrioid carcinomas were CK-7 positive. EMA was positive in all carcinomas but negative in the SCTAT, AGCTs. and SLCTs. Inhibin can distinguish between sex cord-stromal tumors (whether granulosa or Sertoli-Leydig type) and endometrioid carcinomas. CK-7 is also helpful in differentiating between AGCTs and most endometrioid carcinomas, and may also aid in separating SLCTs from sertoliform carcinomas. The addition of inhibin to an antibody panel is important because it provides a positively-staining marker for sex cord-derived cells.

Correlation of DNA ploidy and S‐phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma

DNA ploidy and S‐phase fraction were measured by flow cytometry in the tumour tissue of 87 patients with disseminated malignant melanoma, who had been classified either as responders or with progressive disease in a study of the effects of 2 chemotherapeutic regimens. The patients had been randomized to receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or without addition of cisplatin (Platinol). Tumour tissue was obtained from both the primary tumours and the last histologically verified metastases, but in some cases only the primary tumours or the last metastases could be evaluated. There was a significantly higher mean S‐phase value in melanoma metastases from patients with complete or partial responses compared with patients with progressive disease. Neither the S‐phase fraction of the primary tumour, nor the DNA ploidy of the primary tumour or of the last histologically verified metastases taken before inclusion into the study were associated with therapeutic response. In the multivariate analysis, both the anatomical location of the metastases and the S‐phase fraction measured on the last metastases remained significant prognostic factors of response. In the univariate survival analysis, there was an association between high S‐phase fractions of the metastases and longer survival. In the multivariate survival analysis, the S‐phase fraction, the number of involved metastatic sites and the treatment response were independent predictive factors. We conclude that, in disseminated melanoma treated with chemotherapy, a high S‐phase fraction measured in the last histologically verified metastases is associated with a higher response rate and a longer survival. Our results clearly support the role of S‐phase measurement as a potential tool for selecting patients for treatment.

Increased anal resting pressure and rectal sensitivity in Crohn's disease

PurposeAnal pathology occurs in 20 to 80 percent of patients with Crohn’s disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn’s disease compared with healthy controls. METHODS: Twenty patients with Crohn’s disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations. RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025). CONCLUSIONS: This study demonstrates how patients with Crohn’s disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.

DNA ploidy and S-phase in primary malignant melanoma as prognostic factors for stage III disease

In 82 patients with stage III malignant melanoma, the primary tumours were investigated by DNA flow cytometry. The tumours were classified as DNA diploid (n = 36), tetraploid (n = 11) and aneuploid (n = 35). By univariate analysis a significant correlation with post-recurrence survival was found for time to first metastasis, DNA-ploidy and S-phase fraction. By multivariate analysis, significant prognostic variables were found to be the time to first metastasis (P = 0.006), and ploidy (P = 0.011). Patients with diploid melanomas and a long recurrence-free interval had a median post-recurrence survival time of 45 months compared to 18 months in patients with DNA aneuploid tumours and an early recurrence. The S-phase could be estimated in 47 primary melanomas and was found to be a significant prognostic variable (P = 0.017). The median survival was 45 months for patients with melanomas with a S-phase fraction below 5%, and 19 months for melanomas with S-phase above 10%. The prognostic value of the S-phase remained significant even after adjustment for recurrence-free interval and DNA ploidy.

Tumor necrosis factor-α expression in human primary malignant melanoma and its relationship to tumor infiltration by CD3+ cells

Optimal conditions for immunohistochemical staining of tumor necrosis factor‐A (TNF‐A) in paraffin‐embedded tissue sections were established to investigate TNF‐A expression in human primary malignant melanomas. Seventeen malignant melanomas of the nodular (NMM) and superficially spreading (SSM) subtypes were analyzed. Twelve of these were TNF‐A+, while 5 did not stain for the cytokine. To evaluate how TNF‐A expression affected the immune response to the tumors, infiltration by CD3+ and mac387+ cells was investigated in NMM. TNF‐A expression seemed to selectively affect the capability of T cells to infiltrate the tumors since TNF‐A+ tumors were found to have significantly lower levels of infiltrating CD3+ cells, while there was no difference in numbers of mac387+ cells. These results demonstrate that TNF‐A is variably expressed in primary malignant melanoma in vivo and that the T‐cell response to TNF‐A‐expressing NMM is inhibited.

Endoscopic Total One-Piece Medial Meniscectomy: Its Effect on the Medial Collateral Ligament

Meniscus specimens from 10 patients subjected to endoscopic total medial meniscectomy were examined for remnants of the collateral ligament. Very small amounts were found in the postero-medial area of the specimens. None exceeded 2 mm in length or breadth and could be formed in only one of the sections. With our technique for endoscopic total meniscectomy the integrity of the medial collateral ligament is not violated and ligamentous instability can be avoided.

Arthralgia and Crystal Deposits in Crohn's Disease

Ten patients with Crohns disease and recurrent pain in the knee joints were subjected to arthroscopy. Biopsies obtained from the synovial membrane were examined under polarizing light microscopy. The arthroscopy revealed crystalline deposits in 7 patients and the microscopic examination of the synovial membrane demonstrated positively birefringent crystals in 4 patients. The crystals with positive birefringence had the rod or rhomboid shape typical of pyrophosphate crystals. As arthroscopy crystals in 7 patients and polarizing microscopy revealed crystals in one further patient, crystal deposits were thus found in 8 patients altogether. All patients had normal serum uric acid values. The crystal deposits were interpreted as pyrophosphate and their possible connection with the recurrent arthralgia in Crohns disease is discussed.