Time Of Recurrent Disease Research Articles

Investigating locations of recurrences with MRI after CRS-HIPEC for colorectal peritoneal metastases

PurposePatients with colorectal peritoneal metastases (PM) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are at high risk of recurrent disease. Understanding where and why recurrences occur is the first step in finding solutions to reduce recurrence rates. Although diffusion-weighted (DW) MRI is not routinely used in the follow-up of CRC patients, it has a clear advantage over CT in detecting the location and spread of (recurrent) PM. This study aimed to identify common locations of recurrence in CRC patients after CRS-HIPEC with MRI. MethodThis was a single-centre retrospective study of patients with recurrent PM after CRS-HIPEC performed between January 2016 and August 2020. Patients were eligible for inclusion if they had both an MRI preoperatively (MRI1) and at the time of recurrent disease (MRI2). Two abdominal radiologists reviewed in consensus and categorized recurrences according to their location on MRI2 and in correlation with previous disease location on prior imaging (MRI1) and the surgical report of the CRS-HIPEC. ResultsThirty patients were included, with a median surgical PCI of 7 (range 3–21) at the time of primary CRS-HIPEC. In total, 68 recurrent metastases were detected on MRI2, of which 14 were extra-peritoneal. Of the remaining 54 PM, 42 (78%) occurred where the peritoneum was damaged due to earlier resections or other surgical procedures (e.g. inserted surgical abdominal drains). Most recurrent metastases were found in the mesentery, lower abdomen/pelvis and abdominal wall (87%). ConclusionsMost recurrent PMs appeared in the mesentery, lower abdomen/pelvis and abdominal wall, especially where the peritoneum was previously damaged.

Staphylococcus aureus Skin and Soft Tissue Infection Recurrence Rates in Outpatients: A Retrospective Database Study at 3 US Medical Centers.

BackgroundStaphylococcusaureus skin and soft tissue infections (SA-SSTIs) are common in healthcare and community settings, and recurrences occur at variable frequency, even after successful initial treatment. Knowing the exact burden and timing of recurrent disease is critical to planning and evaluating interventions to prevent recurrent SSTIs.MethodsIn this retrospective study, SSTI cases in patients aged ≥18 years at 3 US medical centers (Columbia, Chicago, Vanderbilt) between 2006 and 2016 were analyzed according to a biennial cohort design. Index SSTIs (with or without key comorbidities), either microbiologically confirmed to be SA-SSTI or not microbiologically tested (NMT-SSTI), were recorded within 1 calendar year and followed up for 12 months for recurrent infections. The number of index cases, proportion of index cases with ≥1 recurrence(s), time to first recurrence, and number of recurrences were collected for both SA-SSTI and NMT-SSTI events.ResultsIn the most recent cohorts, 4755 SSTI cases were reported at Columbia, 2873 at Chicago, and 6433 at Vanderbilt. Of these, 452, 153, and 354 cases were confirmed to be due to S. aureus. Most cases were reported in patients without key comorbidities. Across centers, 16.4%–19.0% (SA-SSTI) and 11.0%–19.2% (NMT-SSTI) of index cases had ≥1 recurrence(s). In patients without key comorbidities, more than 60% of index SSTIs with recurrences had only 1 recurrence, half of which occurred in the first 3 months following primary infection.ConclusionsSA-SSTI recurrences are common among healthy adults and occur in at least 1 in 6 individuals during the 1 year following the primary event.

FOXO3a Mediates Both the Pro-Survival and Proapoptotic Effects of Glucocorticoids In Acute Lymphoblastic Leuekmia

AbstractAbstract 1822Synthetic glucocorticoids (GCs) such as dexamethasone and prednisone are the mainstay of acute lymphoblastic leukemia (ALL) therapy. However, in spite of extensive use of these compounds in treating lymphoid malignancies, the molecular events that lead to cell death upon GC exposure are only poorly understood. Elucidation of these events is crucial to decipher the mechanisms of resistance to GC seen commonly at the time of recurrent disease as well as in older patients diagnosed with ALL and to design therapy targeted to overcome GC resistance. We investigated the molecular events leading to cell death in a panel of ALL cell lines with varying sensitivity to dexamethasone induced cell death. Dexamethasone induced cell death in sensitive cell lines was caspase dependent, preceded by mitochondrial membrane depolarization and cytochrome C release. Since the mitochondrial integrity is controlled by the members of the BCL2 family of proteins, we evaluated the expression of various pro- and anti-apoptotic BCL2 family proteins in ALL cell lines treated with dexamethasone and found a consistent upregulation of Bim, a BH3-only proapoptotic BCL2 family protein. This was accompanied by accumulation of non-phosphorylated FOXO3a, a member of the forkhead transcription factors known to be involved in transcriptional regulation of Bim expression. This accumulation of non-phosphorylated FOXO3a was associated with increased reporter activity in a FOXO-responsive luciferase construct, increased luciferase reporter activity in the Bim promoter containing the canonical foxo response element, and increased occupancy of FOXO3a in the Bim promoter as demonstrated by chromatin immunoprecipitation. However, shRNA mediated partial knock-down of FOXO3a did not rescue ALL cells from dexamethasone induced cell death. Indeed, this partial reduction in FOXO3a levels resulted in sensitization of ALL cells to dexamethasone induced cell death. Similar to the parental or control transfected cells, dexamethasone induced cell death in ALL cells with reduced FOXO3a expression could be inhibited by the pan-caspase inhibitor z-VAD-fmk. Further, the partial reduction in FOXO3a expression did not interfere with Bim up-regulation in response to GC exposure. In addition to modulating apoptosis by transcriptional regulation of molecules like Bim, FOXO family members are also involved in regulating cellular reactive oxygen species (ROS), by transcriptional regulation of molecules like manganese-superxode dismutase involved in ROS scavenging pathways. We therefore measured ROS by dihydroethidium staining in control and FOXO3 shRNA transfected ALL cell lines in the presence or absence of dexamethasone exposure. We found no difference in the ROS levels in the non-treated cells. However, upon exposure to dexamethasone, cells with lower FOXO3a levels demonstrated higher accumulation of ROS when compared to the control cell lines. We conclude that accumulation of non-phosphorylated, active FOXO3a in response to GC exposure mediates both the pro-survival and proapoptotic response in ALL cells and that selective abrogation of the antioxidant, pro-survival functions of FOXO3a might provide a feasible strategy to sensitize ALL cells to GC mediated cell death. Disclosures:No relevant conflicts of interest to declare.

Biphasic metaplastic sarcomatoid carcinoma of the breast

Background: Breast biphasic metaplastic sarcomatoid carcinoma (MSC) is rare and aggressive. We analyzed 100 patients treated at M. D. Anderson Cancer Center (MDACC) with 213 MSC and 98 carcinosarcoma patients identified through the Surveillance, Epidemiology and End-Results (SEER) database to describe clinical and pathologic characteristics.Patients and methods: We searched the MDACC (1985–2001) and SEER databases (1988–2001) for breast MSC and carcinosarcoma patients.Results: We identified 100 MDACC MSC patients: 66% had node-negative disease and 6% distant metastases at presentation. Median recurrence-free survival (RFS) of 94 patients with stages I–III disease was 74 months (range 3–74), with 52% 5-year RFS [95% confidence interval (CI) 0.42–0.63]. Median overall survival in these patients was not reached, with 64% 5-year survival (95% CI 0.54–0.75). The initial stage of the tumor, but not use of adjuvant chemo- or radiotherapy, had a strong association with outcome. The pathologic complete response rate to neoadjuvant chemotherapy was 10%. Median survival from the time of recurrent disease was 14 months (range 1–55). Tumors were usually hormone receptor- and HER2/neu-negative. SEER data were consistent with MDACC findings.Conclusions: Breast MSC and carcinosarcoma are aggressive, treatment-refractory tumors with shared clinical features and outcome similar to poorly differentiated receptor-negative adenocarcinomas. New therapeutic agents are needed.

Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal?

We report the long-term follow-up of 31 patients with cavernous sinus meningiomas who were treated either with surgery and radiotherapy (RT) or with RT alone. This retrospective review was undertaken to compare long-term efficacy and morbidity of RT with or without previous surgery versus complete, aggressive surgical removal. Between 1980 and 1997, we performed a retrospective study of 31 patients harboring cavernous sinus meningiomas. The patient group comprised 25 women and 6 men. Patients were divided into two therapeutic categories: patients treated with surgery and RT (Group I, 17 patients) and patients treated with RT alone (Group II, 14 patients). Twenty-five patients (14 in Group I and 11 in Group II) were treated for primary tumors, and 6 patients (3 in Group I and 3 in Group II) were treated for recurrent disease. All three patients who were treated by RT alone at the time of recurrent disease had had previous surgery as initial treatment. Tumor control, treatment morbidity, and functional outcomes were evaluated for all patients. Twenty-eight patients were alive at the time of analysis, with a median follow-up period of 6.1 years. The progression-free survival rate was 92.8% at 10-year follow-up. Only two patients exhibited tumor progression after initial treatment. One of the patients who experienced tumor regrowth 4 years after surgery and RT benefited from additional conventional external beam radiation, and this patient exhibited no evidence of tumor progression at the last follow-up examination 6 years later. Two patients experienced cranial nerve impairment after surgery, and no patients developed late radiation toxicity. Follow-up status as measured by the Karnofsky Performance Scale deteriorated in 7% of patients and was the same or improved in 93% of patients. The results of combined surgery and RT or RT alone indicated a high rate of tumor control and a low risk of complications. Complete aggressive surgical removal of cavernous sinus meningiomas is associated with an increased incidence of morbidity and mortality and does not demonstrate a better rate of tumor control. Conventional external beam radiation seems to be an efficient and safe initial or adjuvant treatment of these lesions, and these findings should serve as a basis for evaluating new alternatives such as radiosurgery or stereotactic RT.

Secondary Surgery in Ovarian Cancer: A 5-Year Experience

To evaluate the feasibility and role of secondary surgery in ovarian cancer, a retrospective chart review was conducted on 98 patients treated for ovarian carcinoma at our institution between 1992 and 1996. Overall, 80 surgical procedures were performed in 68 patients: 4 patients (5%) underwent reassessment surgery following inappropriate primary surgical procedure; 20 patients (25%) in complete or partial response after first-line chemotherapy underwent interval debulking surgery; 42 patients (52%) without clinical evidence of disease at the completion of first-line chemotherapy underwent second-look laparotomy, and 14 of them received some kind of cytoreduction; 14 patients (18%) underwent cytoreductive surgery at the time of recurrent disease. Secondary surgery in its different forms is feasible in ovarian carcinoma and is associated with a low rate of complications. The proper indication for each of the multiple options for secondary surgery in ovarian carcinoma, however, still remains to be elucidated. (J GYNECOL SURG 14:169, 1998)

Special report. Steroid receptors in breast cancer.

Knowledge of the steroid receptor content of human breast cancer is important for proper diagnosis and for deciding the proper treatment for metastatic disease. Few patients whose breast cancers lack estrogen receptor will benefit from endocrine therapy, while more than half of patients with estrophilin-rich cancers will obtain objective remissions. The probability of objective response to endocrine therapy increases with an increase in the quantity of estrogen receptor in the cancer. Furthermore, patients whose cancers have both estrogen and progestin receptors have a better probability of response than patients whose lesions have only one of the receptors present, although even in such cases the response rate is higher than that seen in patients whose tumors lack both receptors. The data currently available suggest that receptor assays carried out on the primary tumor can be used for prediction of subsequent response to endocrine therapy, even at a later time of recurrent disease. Nonetheless, while sequential assays of receptors in lesions from the same patients are likely to be in agreement, when changes occur they tend to be reductions in amount of receptor or loss of receptor during disease progression . Breast cancer patients with receptor-positive tumors appear to have longer disease-free intervals and prolonged survival when compared with patients whose cancers lack ER, but clearly a part of the prolonged survival relates to response to endocrine therapies. Receptor positivity is frequently associated with well-differentiated tumors, while more poorly differentiated cancers, as well as medullary tumors, in general, and possibly cancers with significant lymphocytic infiltration, are more likely to be receptor negative. While there are some problems reproducing the exact quantitative receptor results among various laboratories assaying the same breast cancer, standard biochemical assays are still the only clinically proven and generally accepted procedure for assessing receptor status of a tumor. Histochemical assays based both on the steroid content of a tumor or using steroid-protein fluorescein complexes, while showing some correlation with standard biochemical assays for estrogen receptor, do not appear to detect receptor protein itself and can not be used instead of standard receptor assays. With the recent availability of monoclonal antibodies to the estrogen receptor, newer assays based on immunochemical procedures are under development and can be expected to provide simpler, less expensive, and more useful biochemical as well as immunohistochemical methods for receptor determination.(ABSTRACT TRUNCATED AT 400 WORDS)