Impact of repeated operations for progressive low-grade gliomas

BackgroundMaximal, aggressive resection of diffuse low-grade gliomas (DLGG) is well established as the standard of care in neuro-oncology. The role of repeat resection for tumor progression is unclear.ObjectiveTo assess the role of repeated operation for DLGG, and the effect on malignant transformation and survival.MethodsWe conducted a historical cohort study in which all patients undergoing multiple resections of DLGG between the years 1995–2019 were evaluated for overall survival (OS) and time to transformation (TTT). We then compared the outcome of this group with that of a matched control group comprised of patients who underwent only one operation despite being eligible for repeat surgery at tumor progression, but had received non-surgical oncological therapy or declined additional treatment.ResultsOf 607 patients in our departmental DLGG database, 93 patients underwent 2 or more surgeries and had sufficient follow-up and imaging data to be included in the study group. Thirty-eight patients were included in the matched control group. Early (less than 1 year) progression was associated with decreased survival and shorter TTT in the study group. Patients undergoing multiple resections had significantly longer TTT and OS compared to patients who underwent a single surgery. This effect was especially noted in patients who had radiological evidence of tumor transformation.ConclusionsRepeated resections of LGG are safe and offer survival benefit in select patients. Early progression following resection is associated with worse prognosis. Patients with evidence of radiological transformation may benefit the most from re-resection.     

原发性支气管粘液表皮样癌12例报告

作者于１９８０年１月～１９９４年１０月收治了１２例原发性支气管粘液表皮样癌，均经手术和病理证实。占同期原发性肺部恶性肿瘤的０．９９％（１２／１２１４）。３年生存率为８０．０％。作者根据临床资料并结合文献复习，认为此瘤是原发性支气管低度恶性肿瘤的一种，手术切除是唯一有效的治疗方法。     

The dose–volume interaction in adult supratentorial low-grade glioma: higher radiation dose is beneficial among patients with partial resection

Purpose To evaluate the hypothesis that adults with partially resected (PR<50% resection) supratentorial low-grade glioma (LGG) benefit from higher doses of radiation. Methods Patients receiving post-operative radiation for WHO grade I–II LGG at the University of Western Ontario between 1979 and 2001 were studied. Patient characteristics evaluated included: age, gender, symptom duration >30 days, seizures at presentation, Karnofsky performance status (KPS) <70, astrocytoma pathology (AS), and radiation dose. A Cox proportional hazard regression model was constructed to test the influence of radiation dose. Results One hundred and seven patients were analyzed. Patients who had PR were not significantly different from those with STR (subtotal/total resection) in terms of patient characteristics. Median survival (MST) of PR patients who received ≤50 Gy was 16.5 months while those who received >50 Gy had a MST of 109.2 months. The interaction of radiation dose and extent of resection was tested after controlling for other patient factors by Cox regression model. The interaction was highly significant for both OS and PFS (P=0.013 and P=0.003, respectively). This model remained significant after excluding six patients receiving doses <42 Gy (OS, P=0.024, and PFS, P=0.001). Conclusions The outcome for patients with LGG is dependent on extent of tumor resection and radiation dose. Patients with PR should be considered for higher radiation dose schedules (>50 Gy). Future trials on therapeutic strategies for LGG should consider stratification of patients by extent of tumor resection. Our data suggests that one dose does not fit all. An erratum to this article can be found at     

Phase II study of low-grade non-Hodgkin lymphomas with fludarabine and mitoxantrone followed by rituximab consolidation: Promising results in marginal zone lymphoma

The majority of patients with indolent lymphomas relapse due to minimal residual disease (MRD). In the present study, we sought to determine whether by using rituximab consolidation, for eradication of MRD, following induction chemotherapy with fludarabine and mitoxantrone (FN) combination could improve the outcome of indolent lymphomas. Patients with indolent lymphoma received fludarabine 25 mg/m² Day 1 - 3 and mitoxantrone 10 mg/m² on Day 1 every 28 days. Patients who attained a response (complete response, CR or partial response, PR) received four weekly doses of Rituximab 375 mg/m² 1 month and 3 months after completion of treatment. Forty-five patients were entered into this Phase II trial. The median follow-up time was 39 months. The median number of delivered cycles was 6. Fifty-three percent of patients attained a CR and 38% a PR for an overall response rate of 91%. One patient had stable disease, one had progression of the disease, whereas 2 were non-evaluable. After a median follow-up of 39 months, 32 of 46 patients (74%) are alive and disease-free. Grade III and IV toxicities included leucopenia (37%), neutropenia (28%), thrombocytopenia (7%), anemia (4%), and diarrhea (2%). Grade V toxicities included septic death in one patient and death due to hepatititis B reactivation 6 months after the last Rituximab dose in another patient. FN followed by R consolidation is a well-tolerated and active regimen in the treatment of patients with indolent lymphomas. Further follow-up is required to determine if these remissions are maintained.     

神经导航辅助幕上低级别脑胶质瘤的手术治疗

背景与目的：低级别胶质瘤在影像学上表现为界限不清,目前治疗仍以手术为主,本研究利用神经导航精确定位的优势。探讨神经导航系统在幕上低级别脑胶质瘤手术中的价值。方法：收集哈尔滨医科大学附属肿瘤医院应用神经导航系统辅助切除幕上低级别脑胶质瘤84例临床资料．并对神经导航应用于低级别脑胶质瘤切除手术的优越性、精确性和注意事项进行分析和总结。结果：本组病例中平均注册误差为1．6,2．9mm。术后近期复查MRI证实全组病例均达到影像学全切除。术后症状改善76例（95％）;症状无改善7例;加重1例,且在短时间内恢复。结论：神经导航系统可以精确定位并确定手术切除范围,有利于幕上低级别脑胶质瘤的全切除率及降低手术并发症的发生。     

An extraordinary case in whom gastrointestinal stromal tumor and low-grade malignant lymphoma are seen together in the stomach

Introduction Gastrointestinal system (GIS) is the most common site of involvement of all primary extranodal lymphomas. Gastric lymphoma constitutes 3–6% of all primary stomach malignancies. Stomach is also the commonest site of involvement of gastrointestinal stromal tumors (GIST). We would like to report these rare synchronous tumors in the same patient. Case A 68-year-old male was admitted to the internal medicine clinics with the complaints of abdominal distension. Physical examination was normal. On abdominal computed tomography a 12 × 14 × 22 cm sized giant tumoral mass was detected in left hypochondrium. A total gastrectomy was performed. Two distinct neoplasms were detected; one of which was located in the posterior wall of the stomach with the size of 24 × 16 × 13 cm, and the other one was localized in the fundus of the stomach and its size was 6 × 5 × 2 cm. Pathological evaluation revealed the diagnosis of GIST at the posterior wall and low-grade malignant lymphoma from the mass localized in the fundus of the stomach. Discussion Two primary tumors are not seen so often together in the stomach. Adenocarcinoma and associated tumors including gastric lymphoma (especially MALT lymphoma), carcinoid, leiomyosarcoma and rhabdomyosarcoma constitute most of the reported series. Rarely adenocarcinoma and associated GIST cases were reported. It is important to report concurrent gastric lymphoma and GIST case since it is extremely rare in the English literature.     

低级别胶质瘤的治疗

低级别胶质瘤占胶质瘤的15%～25%,生物学特性及临床预后相差较大。如何治疗低级别胶质瘤仍存在较大争议。根据大宗的文献资料,从循证医学的角度考虑,目前多数认为,手术切除肿瘤能够明确病理、缓解肿瘤的占位症状和延缓病情的进展,除症状不明显、全身情况差或肿瘤位于脑干等深部重要功能区的患者外,多宜行手术。手术应在最大限度保全神经功能的前提下尽可能彻底切除肿瘤,对切除肿瘤确有困难的也应尽可能做活检(包括立体定向活检)。术后应在72小时内复查MRI,明确肿瘤切除程度。放疗在低级别胶质瘤治疗中的作用逐渐被肯定。除年龄小于40岁,以癫痫为主要临床表现,且手术后影像学证明肿瘤切除彻底的患者外,其他低级别胶质瘤患者建议行术后放射治疗。在化疗方面,传统的PCV方案及不良反应较小的口服化疗药替莫唑胺,对低级别胶质瘤显示出一定的疗效,但仍需进行深入的研究。此外,分子靶向治疗及生物治疗等手段也被考虑应用于低级别胶质瘤的治疗,但还有待前瞻性的临床研究。     

Management of minor cervical cytological abnormalities: a systematic review and a meta-analysis of the literature

BACKGROUND: A significant number of women are diagnosed with a low grade cytological abnormality on cervical screening. Many authorities recommend surveillance as spontaneous regression might occur. However, protracted attendance for cytological follow-up decreases with time and might put some women at risk of developing invasive disease. The aim of this review was to assess management options for women with minor cervical disease. METHODS: An electronic literature search was conducted. All randomised controlled studies comparing immediate colposcopy to cytological surveillance in women with cervical atypia/borderline nuclear changes or low-grade lesions were included. The main outcomes studied were the default rates from the colposcopy clinic and the histological status of biopsies within immediate management protocols compared to biopsies taken on completion of surveillance. Pooled relative risks and 95% confidence intervals were calculated using a random-effect model and inter-study heterogeneity was assessed with Cochrane's Q-test. RESULTS: Three randomised controlled trials identified from the literature search with different surveillance periods were combined. The analysis revealed that compliance with follow-up declines over time and reaches significance at the end of 24 months of surveillance (RR: 74.10 [10.36, 529.79]). There was a significantly higher incidence of HPV and CIN 1 in those women referred to immediate colposcopy/treatment compared to those at the end of 24 months surveillance period (32% vs 21%) (RR 1.49, 95% CI 1.17-1.90) and (21% vs 8%) (RR 2.58, 95% CI 1.69-3.94), respectively, possibly explained by spontaneous regression of clinically non-important lesions. Finally, there was no significant difference in the incidence of CIN2 or worse at initial colposcopy compared with the observation group (24 months) (RR 1.72, 95% CI 0.85-3.48). CONCLUSION: Cytological surveillance puts women at risk as many show poor compliance and such women might have occult high grade abnormalities. A general policy should be immediate colposcopy for all women after a single low grade cervical smear.     

Regression of follicular lymphoma with Devil’s Claw: coincidence or causation?

Background

Cancer patients frequently use alternative therapies. Two follicular lymphoma patients who had objective tumour regression after taking Devil’s Claw without cytotoxic therapy are reported here.

Methods and Results

Patient 1 presented with coexistent immunoglobulin G plasma cell dyscrasia and stage iiia lymphoma (nodes 5 cm in diameter). Computed tomography scan 10 months later showed partial regression. On enquiry, it was learned that the patient was taking Devil’s Claw and Essiac (Essiac Products Services, Pompano Beach, FL, U.S.A.). This patient later developed overt myeloma, at which time he stopped the herbal supplements and underwent high-dose chemotherapy and stem cell transplantation, since which no lymphoma progression has occurred. Patient 2 presented with stage iiia lymphoma (nodes 2.5 cm in diameter). He learned of patient 1 through our lymphoma patient support group and started Devil’s Claw. Computed tomography scan 11 months later showed decreased adenopathy and splenomegaly, which has been sustained for 4 years.

Discussion and Conclusions

Devil’s Claw tuberous root has anti-inflammatory properties, probably through suppression of cyclooxygenase 2 (cox-2) and inducible nitric oxide synthase expression. There are no prior reports of anticancer activity. Inhibition of cox-2 has a role in colon cancer prevention, has been implicated in lymphomagenesis, and is associated both with lymphoma stage and with response to treatment. However, spontaneous regression in lymphoma has been reported in 16% of patients in one series, of whom none were on herbal medications or cox-2 inhibitors. The key issue in both these patients is whether disease regression was “spontaneous” or causally related to therapy with Devil’s Claw. The timing of the response suggests a positive effect. Further investigation is warranted, preferably with a cox-2 inhibitor of known purity.     

Current concepts in the evaluation and management of WHO grade II gliomas

Over the past two decades, the accumulated clinical and research experience has improved our understanding the biology of WHO grade II gliomas (G2G). While there have been relatively few randomized clinical trials in this population, those that exist and the experience from clinical reports have enhanced our understanding of how these tumors progressively increase in size, accumulate additional genetic mutations and ultimately transform into high-grade lesions. Our ability to reliably predict the time sequence of this transformation remains a challenge; however, recent findings have started to clarify selection criteria for adjuvant treatment. G2G remain a fatal disease for many patients. Continued investigation into the biology of these lesions will likely provide the information needed to select more appropriate therapy based on biological and genetic differences in these unique lesions. Some of this information will be derived from the study of high-grade lesions. However, experience has shown that much of the work on high-grade lesions is also applicable to low-grade lesions.     

The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

Purpose In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. Patient and methods Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. Results LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. Conclusion LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits. This study was supported by Schering Plough Nederland and the Kapteijnfonds.     

Correlation between MIB-1 staining indices and recurrence in low-grade astrocytomas

Although low-grade astrocytomas are histologically benign, some of them recur frequently. We retrospectively investigated the relationship between MIB-1 staining index (SI) and recurrence in 47 low-grade astrocytomas that were treated in Keio University Hospital from 1981 to 1991. We found a correlation between SI and recurrence. MIB-1 SIs recurrent low-grade astrocytomas have been shown to be almost similar to those of astrocytoma grade 3. We concluded that it was very important to examine MIB-1 SI in all astrocytomas especially in low-grade astrocytomas, because MIB-1 SI is one of the factors from which we could predict recurrence and decide whether radiotherapy or chemotherapy should be performed.     

Effectiveness of novel combination chemotherapy, consisting of 5-fluorouracil, vincristine, cyclophosphamide and etoposide, in the treatment of low-grade gliomas in children

Low-grade gliomas (LGG), which account for about 30% of brain tumors in children, are usually treated with surgical excision and/or radiotherapy. For patients who have significant residual tumor after resection or relapse after radiation, the proper chemotherapy regimen has not yet been identified. Thirteen children diagnosed with LGG outside the cerebellum between January 1999 and December 2004, all of whom had significant residual tumor after surgical resection, relapsed after radiation or showed visual deterioration, were treated for 18 months with a multi-drug regimen of vincristine, etoposide, cyclophosphamide and 5-fluorouracil. Of the 7 patients who completed chemotherapy, 1 showed complete response (CR), 5 showed partial response (PR), and 1 had stable disease (SD). In 5 patients, chemotherapy was prematurely discontinued; 4 of these patients showed tumor progression and 1 had SD. One patient is still undergoing treatment. The side effects of chemotherapy were manageable. The median time to tumor response was 34 months (range, 2–82 months). The progression free survival was 67.3%. Pediatric LGG patients with residual tumor after surgery or who undergo relapse(s) may be successfully treated using our combination chemotherapy regimen.     

Radical surgery after chemotherapy: a new therapeutic strategy to envision in grade II glioma

While surgery is proned in low-grade glioma (LGG), the invasion of functional areas frequently prevents a complete resection. We report the first case of a patient operated on for a left frontal LGG, diagnosed because of seizures, with partial resection due to an invasion of the controlateral hemisphere. Chemotherapy enabled a regression of this controlateral extension. Postchemotherapy surgery performed with intraoperative functional mapping then allowed a complete resection, without sequelae. The patient has a normal socio-professional life, with no seizure. No other treatment was given. There was no recurrence, with a follow-up of 2 years since the second surgery (3.5 years since the first symptom). We propose a new therapeutic strategy in unresectable LGG, with preoperative chemotherapy, to make a radical surgery possible in a second step, while preserving the quality of life.