Unraveling the genetics of transformed splenic marginal zone lymphoma.

The genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P = .001; P = .042; and P = .007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event.

The scintigraphic index spleen/liver at 30 minutes predicts the success of splenectomy in persistent and chronic primary immune thrombocytopenia.

UNLABELLED: Splenectomy is considered the second-line of treatment in patients with chronic primary immune thrombocytopenia (ITP) in whom glucocorticoids have failed. Some patients do not respond to splenectomy or they have postoperative complications. Based on our previous experience using kinetic and scintigraphic parameters, we did a retrospective study with the aim of comparing all these parameters as a means of predicting the success of splenectomy in persistent and chronic primary ITP. Forty-one consecutive patients with chronic primary ITP refractory to prednisone, who had been splenectomized, were included in the study. The response to splenectomy was assessed by evaluating bleeding and platelet counts before and at different times after surgery. A complete platelet kinetic study was performed before the splenectomy using autologous (111) In-labeled platelets. The scintigraphic parameters measured included different indices between spleen/heart, liver/hearth, and spleen/liver. Thirty-six patients gave a complete response after splenectomy and five patients did not respond. A statistically significant difference between both groups was found with initial platelet recovery and with some scintigraphic indices which also showed a variable prediction value for the success of splenectomy. Among these indices, the spleen/liver at 30 minutes demonstrated a predictive value with a 100% of sensitivity and a 100% of specificity. CONCLUSION: some platelet kinetic parameters and scintigraphic indices, in particular the spleen/liver at 30 minutes, were useful to predict the outcome of splenectomy in persistent and chronic primary ITP and, therefore, they should be taken into account when deciding whether or not to perform a splenectomy.

Gn-RH antagonists in intrauterine insemination: the weekend-free protocol.

OBJECTIVE: To compare the results of intrauterine insemination (IUI) when GnRH antagonist was added-to avoid IUI on weekend-with those obtained with the standard IUI protocol. STUDY DESIGN: In an IUI program under ovarian stimulation with gonadotropins when one or more follicles of 15-16 mm were seen, if it was not possible for logistic reasons (weekend) to perform the insemination 72 h later, GnRH antagonist was administered until human chorionic gonadotropin (hCG) administration. The IUI was performed on Monday. We compared the results of this IUI "weekend-free'' group with our results in standard IUI cycles, where IUI was performed 36-38 h after reaching optimal follicular growth. RESULTS: Both groups were comparable regarding the main demographic parameters, except for higher estradiol levels, due to the prolonging ovarian stimulation. The per cycle pregnancy rate (PR) were very similar in both groups: 15.7% in the weekend-free IUI versus 16.5% in standard IUI. The multiple pregnancy rate and the hyperstimulation rate were also similar. A non-significant trend to higher high-order multiple pregnancy was observed in the weekend-free IUI. CONCLUSIONS: In IUI cycles under ovarian suprastimulation with gonadotrophins, the use of GnRH antagonist allows the manipulation of the follicular development in such a way that it is possible to avoid inseminations on the weekends, without apparently reducing the PR.

Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy.

OBJECTIVE: To estimate the risk of recurrence after administration of hormone replacement therapy (HRT) among women who have had endometriosis and who underwent bilateral salpingo-oophorectomy (BSO). DESIGN: Prospective randomized trial (115 women receiving HRT and 57 not receiving HRT). SETTING; Public university hospital. PATIENT(S): Women with a histologic diagnosis of endometriosis in whom BSO was performed; 91.8% had a total hysterectomy. INTERVENTION(S): Periodical clinical examination, vaginal ultrasound, and CA-125 levels; surgical evaluation and histologic study. MAIN OUTCOME MEASURE(S): Recurrence rate, prognostic factors, and a mean follow-up time of 45 months. RESULT(S): There was no recurrence among women who did not receive HRT, versus a 3.5% rate (4 out of 115), or 0.9% per year, in women who received HRT. Two recurrences required abdominal surgery. There was one additional patient who required surgery, but the relationship to the endometriosis recurrence was controversial. Among women receiving HRT, the following risk factors were detected: peritoneal involvement > 3 cm (2.4% recurrence per year vs. 0.3%) and incomplete surgery (22.2% per patient vs. 1.9%). CONCLUSION(S): Patients with a history of endometriosis in whom total hysterectomy and bilateral salpingo-oophorectomy have been performed have a low risk of recurrence when HRT is administered. In those patients, HRT is a reasonable option. However, in cases with peritoneal involvement > 3 cm, the recurrence rate makes HRT a controversial option; if HRT is indicated, it should be monitored closely.