Second Surgery For Recurrence Research Articles

EP07.01-022 Analysis of Second Surgery for Recurrence in Malignant Pleural Mesothelioma (MPM) Patients (P)

MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. Recently immunotherapy have demonstrated survival benefit in first line. Currently there is no universally accepted surgical therapy for MPM and it remains unclear whether cytoreductive surgery prolongs survival. Some reports on selected patients demonstrated that, at the progressive disease, second round surgery is an effective strategy with minimal morbidity and promising survival rates.

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P<.001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P<.001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P<.001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.

Rate of conversion from unresectable to resectable metastatic colorectal cancer (mCRC) in real-world patients (RWP) treated with FOLFIXIRI ± bevacizumab: A population-based retrospective cohort study.

21 Background: Recent evidence from randomized trials suggests that FOLFOXIRI (5FU, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates with a potential for conversion of unresectable to resectable disease in mCRC. Yet limited evidence is available about efficacy and safety of this regimen in RWP with mCRC. The current study aims to evaluate conversion rate and safety of FOLFOXIRI ± bevacizumab in RWP with unresectable mCRC. Methods: Each year about 175 patients are diagnosed with mCRC in Saskatchewan. Patients who were diagnosed with unresectable mCRC between Jan 2015 to Dec 2018 and received FOLFOXIRI ±bevacizumab were assessed. Kaplan Meier survival methods and log rank test were performed. Logistic regression analysis was performed to assess factors correlate with conversion. Results: 28 eligible patients with median age of 51 yrs (IQR:39-60) and M:F of 11:16 were identified. 42% patients had a comorbid illness, and 43% had WHO performance status of 0. 39% had rectal cancer, 46% had extrahepatic disease and 46% had bilobar liver metastases. 58% patients had a positive response to therapy, 60% had grade 3/4 toxicity &amp; 32% required hospital admission. No treatment-related mortality was noted. 54% patients underwent metastasectomy (liver 73%, peritoneum and or ovaries 20%, lung 6%). 68% had primary tumor resection, 29% received rectal radiation, 21% had ablation and 18% had second surgery for recurrence. At 4 years 50% patients are alive. Median progression free survival of patients who underwent surgery is 18 (95%CI:11.3-24.7) vs. 11 months (4-18.1) without surgery (P = 0.28). Median overall survival of patients with surgery is 33 (17.5-48.5) vs. 16 months (8.3-23.7) without surgery (P = 0.03). Positive response to treatment is correlated with conversion (odd ratio 21.7, p = 0.002). Conclusions: In the real world setting younger patients with good performance status received FOLFIRINOX ± bevacizumab. Despite high rates of toxicity, more than half of patients were able to undergo surgery. A positive response to treatment significantly correlates with metastasectomy.

Clinicopathologic features of anaplastic myxopapillary ependymomas.

Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in a small subset. To our knowledge, only five anaplastic MPEs have been reported without consensus on diagnostic criteria. We retrieved 14 anaplastic MPEs from the pathology archives of six institutions. Each tumor included at least two of the following features: ≥5 mitoses per 10 high power fields, Ki-67 labeling index (LI) ≥10%, microvascular proliferation (MVP) and spontaneous necrosis. These features were typically encountered in the foci of hypercellularity and reduced mucin. There were eight male and six female patients (age range 6-57 years, median = 16.5). Ten tumors displayed anaplasia at initial resection, and 4 were anaplastic at a second surgery for recurrence (ranging from 9 months to 14 years following initial resection). The Ki-67 LI ranged between 8% and 40% in the anaplastic foci and <3% in the foci of classic MPE. There was documented cerebrospinal fluid (CSF) dissemination in seven cases, recurrence following an anaplastic diagnosis in three cases and bone or soft tissue invasion in two cases. One patient suffered lung metastases. Two cases evaluated by targeted next-generation sequencing and one evaluated by fluorescence in situ hybridization (FISH) showed nonspecific chromosomal gains. We conclude that although rare, anaplastic MPE occurs in both pediatric and adult patients, similar to other ependymomas. At a minimum, closer follow-up is recommended, given the concern for aggressive biologic potential. Further study is needed to determine WHO grading criteria and genetic indicators of tumor progression.

Examination of cases that required a second surgery for recurrence after tympanoplasty

Examination of cases that required a second surgery for recurrence after tympanoplasty

The paramedian supracerebellar-transtentorial approach to the entire length of the mediobasal temporal region: an anatomical and clinical study

The exploration of lesions in the mediobasal temporal region (MTR) has challenged generations of neurosurgeons to achieve an appropriate approach. To address this challenge, the extensive use of the paramedian supracerebellar-transtentorial (PST) approach to expose the entire length of the MTR, as well as the fusiform gyrus, was investigated. The authors studied the microsurgical aspects of the PST approach in 20 cadaver brains and 5 cadaver heads under the operating microscope. They evaluated the features, advantages, difficulties, and limitations of the PST approach and refined the surgical technique. They then used the PST approach in 15 patients with large intrinsic MTR tumors (6 patients), tumor in the posterior fusiform gyrus with mediobasal temporal epilepsy (MTE) (1 patient), cavernous malformations in the posterior MTR including the fusiform gyrus (2 patients), or intractable MTE with hippocampal sclerosis (6 patients) from December 2007 to May 2010. Patients ranged in age from 11 to 63 years (mean 35.2 years), and in 9 patients (60%) the lesion was located on the left side. In all patients with neuroepithelial tumors or cavernous malformations, the lesions were completely and safely resected. In all patients with intractable MTE with hippocampal sclerosis, the anterior two-thirds of the parahippocampal gyrus and hippocampus, as well as the amygdala, were removed selectively through the PST approach. There was no surgical morbidity or mortality in this series. Three patients (20%) with high-grade neuroepithelial tumors underwent postoperative radiotherapy and chemotherapy but needed a second surgery for recurrence during the follow-up period. In all patients with MTE, antiepileptic medication could be decreased to a single drug at lower doses, and no seizure activity has occurred until this point. The PST approach provides the surgeon precise anatomical orientation when exposing the entire length of the MTR, as well as the fusiform gyrus, for removing any lesion. This is a novel technique especially for removing tumors involving the entire MTR in a single session without damaging neighboring neural or vascular structures. This approach can also be a viable alternative for selective removal of the parahippocampal gyrus, hippocampus, and amygdala in patients with MTE due to hippocampal sclerosis.

Giant Pituitary Adenomas

Giant pituitary adenomas, with diameter ≥4 cm, were formerly considered rare and not surgically approachable. Few United States-based series exist. We reviewed our 10-year experience with these tumors and identified 17 patients, 11 male and 6 female, aged 27 to 65 years. Twelve of 17 cases were either gonadotroph or null cell adenomas and 5 were giant prolactinomas. By neuroimaging, all invaded the cavernous sinus(es) and tumors in 13 patients invaded the skull base. Despite massive size, only 5 showed apoplectic clinical and neuroimaging features. When present, this feature occasionally prompted preoperative consideration of craniopharyngioma. Transsphenoidal surgical excision was possible in all patients, with 3 undergoing planned second-stage reoperations and 2 requiring a second surgery for recurrence (both at 6-year intervals). Despite the aggressive features of massive size and cavernous sinus invasion, mitotic rates and immunohistochemistry (IHC) labeling for p53 and MIB-1, features alleged to be associated with atypical adenomas, were minimally increased. Absence of a role for TP53 and cell cycle markers was further verified on a subset of our cases by microarray and quantitative reverse transcription polymerase chain reaction analyses. Five giant gonadotroph adenomas were compared with 7 nonaggressive, nongiant gonadotroph cell adenomas, and no statistically significant changes in transcript levels of MIB-1 (MKI67) or TP53 were observed. A number of other genes, however, did show differential gene expression. In conclusion, most giant pituitary adenomas are gonadotroph cell adenomas or giant prolactinomas in men. Microarray profiling validates the IHC impression that MIB-1 and p53 IHC do not correlate with aggressive features in the most common type of giant adenoma.

O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications.

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

Near total thyroidectomy is an optimal treatment for graves’ disease

Surgical management of Graves' disease is still debated. We report our current experience with thyroidectomy for Graves' disease at a tertiary center. A retrospective database of 132 patients who underwent surgery for Graves' disease from January 1985 to December 2008 was collected. During that period, 16 patients underwent subtotal thyroidectomy and 116 patients underwent near total thyroidectomy. Eighty-seven patients (66%) underwent surgery for recurrent disease after medical therapy. Forty-five patients (34%) had surgery as a primary treatment, the indications were large goiter size in 22 (17%), patient preference in 19 (14%), and associated cold nodule in 3 (2%). The incidence of cancer was 4.4%. Permanent hypoparathyroidism was observed in one patient who underwent a second surgery for recurrence. Unilateral transitory vocal cord palsy was observed in nine patients (7%), bilateral transitory vocal cord palsy was observed in one patient, and no definitive vocal cord palsy was observed. Two patients (1.5%) experienced post-operative hemorrhagia requiring surgical revision. Near total thyroidectomy for Graves' disease provides an immediate and definitive treatment with a low complication rate. Near total thyroidectomy offers an appropriate treatment for coexisting malignancy. This procedure can be safely recommended as a primary treatment, in experienced hands.

8705 Change in MGMT methylation status between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications

8705 Change in MGMT methylation status between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications

Change in MGMT methylation status between first and second surgery for recurrence: Clinical implications

2027 Background: MGMT promoter methylation status is known to be a potent prognostic factor in newly diagnosed glioblastoma (GBM) patients (pts). However, it is not yet clear whether and, if so, how MGMT methylation status may change; nor is it known whether the prognostic role of this epigenetic feature is retained during the disease course. Methods: A retrospective analysis was made using a database of 614 GBM pts treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age ≥18; PS 0–2; two distinct surgical procedures; histological diagnosis of GBM both at first and at second surgery for recurrence; postoperative treatment consisting of: a) radiotherapy (RT) followed by temozolomide (TMZ) until 2005, and b) TMZ concurrent with and adjuvant to RT after 2005; a time interval ≥3 month between first and second surgery. The study aim was to evaluate changes of MGMT status during the course of GBM. The log-rank test was employed to evaluate the significance of the prognostic variables. The percentages of MGMT methylated cases at first and second surgery were compared using the McNemar test. Results: MGMT status, evaluated at first and second surgery in all 44 pts (M:F 32:12, median age: 49 years, range: 27–67), was assessable in 38 (86.4%) cases: MGMT promoter was methylated in 13 (34.2%) pts at first surgery. MGMT methylation status, unchanged in 63.2% of second surgery samples, changed more frequently in methylated than in unmethylated pts (61.5% vs 24%, p = 0.03). The median survival was 24.3 months (95% CI: 20.8–27.7), being 35.2 months (95% CI: 10.1–60.2) and 21.9 months (95% CI: 17.3–26.5) for pts with methylated and unmethylated MGMT assessed at first surgery, respectively (p = 0.04). However, MGMT status at second surgery was no longer prognostic for survival (p = 0.1). Conclusions: Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. Moreover, while MGMT methylation status is prognostic at first surgery, it appears to be of no prognostic utility at the time of second surgery. No significant financial relationships to disclose.