MarginProbe® – Final results of the German post-market study in breast conserving surgery of ductal carcinoma in situ

The goal in breast conserving surgery (BCS) of ductal carcinoma in situ (DCIS) is removal of the tumor with a clear surgical margin. However, re-excision rates are regrettably high. To date, there are no adequate procedures for intraoperative margin assessment of DCIS. A multicenter, single arm study was conducted to evaluate the benefit of a novel device (MarginProbe^®) in intraoperative margin assessment during BCS of DCIS, the associated reduction of re-excisions and the cosmetic outcome of the treated patients. We present results of 42 patients enrolled in 3 German institutions. The device was used as an adjunctive tool to standard of care. The device use was associated with a reduction in re-excision rates by 56%, from 39% to 17% (p = 0.018).     

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations

IntroductionThe potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice.MethodsA panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach.ResultsAccording to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence).DiscussionThis review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values.Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.     

Intracystic papillary carcinoma of the breast: An in situ or invasive tumor? Results of immunohistochemical analysis and clinical follow-up

Intracystic papillary carcinoma (IPC) is regarded as an intraductal neoplasm, but recent evidence suggests that it could be invasive, as it often lacks myoepithelial lining. We evaluated myoepithelial cells and collagen IV, a basement membrane component, in 40 IPCs from 39 (35 female and 4 male) patients and assessed their clinical management and follow-up. The mean patient age at diagnosis was 68 years, and the mean tumor size was 1.8 cm. Thirteen cases were pure IPC, 8 cases were IPC with or without microinvasion, and 19 cases were IPC with invasive carcinoma (IPC+IC), including 1 mucinous and 1 cribriform carcinoma. Ductal carcinoma in situ associated more often with IPC+IC (84.2%) than with pure IPC (61.5%) or IPC with or without microinvasion (62.5%). Myoepithelial cells were completely absent in 33 of 40 (82.5%) IPCs, and only focal in the remaining 7 of 40 cases (17.5%). Collagen IV lining was discontinuous in most cases (89%). All tumors were estrogen receptor positive and HER2 negative; most were progesterone receptor positive (93%). Eleven patients underwent mastectomy and 28 lumpectomy; 3 of 27 (11%) patients had lymph node involvement. Fourteen of all patients treated with breast conservation received radiation, 10 hormonal treatment, and none chemotherapy. Four patients treated conservatively (3 with pure IPC and 1 with IPC+IC) recurred locally, including one who later developed bone metastasis. We conclude that IPC constitutes a spectrum of intraductal and IC, with predominance of the latter. IPC rarely involves lymph nodes and carries very good prognosis, but can recur locally. This type of tumor is strongly estrogen receptor positive and hormonal therapy should be pursued for its management, whereas the benefit of radiation after lumpectomy remains unclear.     

ACR Appropriateness Criteria® conservative surgery and radiation--stage I and II breast carcinoma: expert panel on radiation oncology: breast

Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long-term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments.     

Positive anterior margins in breast conserving surgery: Does it matter? A systematic review of the literature

Positive margins are associated with an increased risk of ipsilateral breast tumor recurrence (IBTR); therefore re-excision of positive margins is recommended. Involvement of anatomically non-breast margins, such as anterior margins, has been associated to a lower risk of IBTR than radial margins. Although many surgeons do not re-excise positive anterior margins (PAM); there is no consensus regarding this approach. The objective of this study is to find evidence that assesses this practice.A systemic literature review was performed through six databases from January 1995 to July 2014. Studies that discussed anatomical location of involved margins in BCS were included.Six studies were identified evaluating PAM. One study reported a 2.5% rate of IBTR in patients with non-negative margins treated with radiotherapy (of which 23% had a PAM). Another study showed 4% of residual disease after re-excision of PAM, but did not report IBTR rates. A later observational study reported that 87.5% of positive anterior and posterior margins were re-excised. One survey from America and one from the UK showed that 47% and 71% of surgeons would not re-excise PAM, respectively. A later survey in the UK reported that 43.8% of surgeons would not re-excise PAM in DCIS, whilst 29.2% would not for invasive carcinoma.Common surgical practices to not re-excise PAM contradict current guidelines that recommend obtaining negative margins to reduce the risk of IBTR. However, there is little evidence detailing the relationship between PAM and IBTR rates. Low residual disease after re-excision of PAM supports the limited benefit of re-excise this margin; however further studies are required to evaluate this topic.     

Accelerated partial breast irradiation with 3-dimensional conformal and image-guided intensity-modulated radiotherapy following breast conserving surgery – 7-Year results of a phase II trial

PurposeTo present the 7-year results of accelerated partial breast irradiation (APBI) using three-dimensional conformal (3D-CRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS).Patients and methodsBetween 2006 and 2014, 104 patients were treated with APBI given by means of 3D-CRT using 3–5 non-coplanar, isocentric wedged fields, or IG-IMRT using kV-CBCT. The total dose of APBI was 36.9 Gy (9 × 4.1 Gy) using twice-a-day fractionation. Survival results, side effects and cosmetic results were assessed.ResultsAt a median follow-up of 90 months three (2.9%) local recurrences, one (0.9%) regional recurrence and two (1.9%) distant metastases were observed. The 7-year local (LRFS), recurrence free survival was 98.9%. The 7-year disease-free (DFS), metastases free (MFS) and overall survival (OS) was 94.8%, 97.9% and 94.8%, respectively. Late side effects included G1 skin toxicity in 15 (14.4%), G1, G2, and G3 fibrosis in 26 (25%), 3 (2.9%) and 1 (0.9%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 10 (9.6%) patients. No ≥ G2 or higher late side effects occurred with IMRT. The rate of excellent/good and fair/poor cosmetic results was 93.2% and 6.8%, respectively.Conclusion7-year results of APBI with 3D-CRT and IG-IMRT are encouraging. Toxicity profile and local tumor control are comparable to other series using multicatheter interstitial brachytherapy. Therefore, these external beam APBI techniques are valid alternatives to whole breast irradiation and brachytherapy based APBI.     

Late gastrointestinal morbidity in patients with stage I–II testicular seminoma treated with radiotherapy

ObjectivesTo define the incidence and risk factors for late gastrointestinal (GI) morbidity in patients with testicular seminoma treated with radiotherapy (RT).Methods and materialsA retrospective review was conducted of 251 patients with stage I or II testicular seminoma treated with curative-intent RT at our institution from 1974 to 2009. All patients underwent orchiectomy and postoperative external beam RT to the involved nodal basin or at-risk nodal basin or both. Potential late GI morbidities that were assessed included endoscopically confirmed peptic ulcer disease (PUD), small bowel obstruction (SBO), and biopsy-confirmed malignancy of the GI tract. The probabilities of these GI morbidities were estimated with the Kaplan-Meier method. Univariate analyses were performed to examine for associated predictive factors using the Cox proportional hazards model.ResultsMedian age at diagnosis was 36 years (range 18–80). Clinical stage was I (n = 199) or II (n = 52). Median abdominopelvic RT dose was 26 Gy (interquartile range = 25–30). Median follow-up was 15 years (range = 0.1–38). PUD risk at 10, 20, and 30 years was 4%, 7%, and 9%, respectively. Age at diagnosis (per y, HR = 1.05, 95% CI 1.00–1.09, P = 0.04) and RT dose (per Gy, HR = 1.20, 95% CI 1.09–1.31, P<0.01) were associated with risk of PUD. SBO risk at 10, 20, and 30 years was 2%, 2%, and 3%, respectively. History of inflammatory bowel disease was associated with risk of SBO (HR = 43, 95% CI 7–325, P<0.01). GI second malignancy risk at 10, 20, and 30 years was 0.5%, 3% and 16%, respectively. Age at RT was associated with risk of GI malignancy (per y, HR = 1.07, 95% CI 1.02–1.14, P = 0.01).ConclusionsIn this patient population, late GI morbidity was relatively uncommon, but clinically significant. Refinements of treatment strategies may reduce this risk.     

The role of postoperative radiation therapy in stage I–III male breast cancer: A population-based study from the surveillance,epidemiology, and End Results database

BackgroundThis study aimed to investigate the role of postoperative radiation therapy in a large population-based cohort of patients with stage I–III male breast cancer (MaBC).MethodsPatients with stage I–III breast cancer treated with surgery were selected from the Surveillance, Epidemiology, and End Results cancer database from 2010 to 2015. Multivariate logistic regression identified the predictors of radiation therapy administration. Multivariate Cox regression model was used to evaluate the predictors of survival.ResultsWe identified 1321 patients. Age, stage, positive regional nodes, surgical procedure, and HER2 status were strong predictors of radiation therapy administration. There was no difference between patients who received radiation therapy and those who did not (P = 0.46); however, after propensity score matching, it was associated with improved OS (P = 0.04). In the multivariate analysis of the unmatched cohort, the factors associated with better OS were administration of radiation therapy and chemotherapy. In the subset analysis of the unmatched cohort, postoperative radiation therapy was associated with improved OS in men undergoing breast-conserving surgery (BCS), with four or more node-positive or larger primary tumours (T3/T4). Furthermore, we found no benefit of radiation therapy, regardless of the type of axillary surgery in mastectomy (MS). In older MaBC patients with T1-2N1 who underwent MS, radiation therapy showed no significant effects, regardless of chemotherapy.ConclusionPostoperative radiation therapy could improve the survival of MaBC patients undergoing BCS, with four or more node-positive or larger primary tumours. Moreover, it should be carefully considered in patients undergoing MS and older T1-2N1 patients.     

Grade 2 chondrosarcoma: stage I or stage II tumor?

We analyzed chondrosarcomas of bone to assess whether Grade 2 tumors are more appropriately grouped with Grade 1 chondrosarcomas or Grade 3 and dedifferentiated chondrosarcomas (Musculoskeletal Tumor Society Stage I or Stage II). A retrospective chart review identified 109 patients who presented with nonmetastatic chondrosarcoma. Data were gathered on each tumor's histologic grade, extent (intracompartmental versus extracompartmental), resection margin status, and site (axial versus appendicular). The cohort included 60 males and 49 females with a mean age of 50 years. Forty tumors were located in the axial skeleton and the remainder were distributed throughout the appendicular skeleton. Fifty-three tumors were Grade 1, 40 tumors were Grade 2, eight tumors were Grade 3, and eight tumors were dedifferentiated. Statistical analysis established grade as the only significant variable for this group of patients; extracompartmental tumor spread also correlated with outcome, but not independent of the grade. Margin status and site were not statistically significant with respect to outcome. Chi-square analysis also established that Grade 2 tumors are grouped more appropriately with the Grade 1 chondrosarcomas as Musculoskeletal Tumor Society Stage I neoplasms. These data should be considered when developing the surgical plan, particularly for patients with Grade 2 appendicular chondrosarcomas.     

Adult primary teratoma of the testis – report on 5 cases in clinical stage I disease

Objectives:Testis pure teratoma accounts for 2.7% to 3% of all germcell tumors in adult where it behaves as a malignant neoplasm. Pureteratoma of the testis presents in clinicalstage I disease in 44% of thepatients whose risk of having pathologicalstage II disease is 16.7% to19.2%. Herein we report on 5 casesof adult pure teratoma of the testispresenting itself in clinical stage I disease.Materials and methods: From September 1976 to February 2000, 75patients underwent orchidectomy for clinical stage I nonseminomatous germcell cancer of the testis. Testis pure teratoma was detected in 5 patients(7%). Testis tumor markers wereevaluated in all cases. Patients underwentimaging examination to detect the clinical stage of the disease. Treatmentoptions after orchidectomy included retroperitoneal lymph node dissection(RPLND) in 4 patients and surveillance in 1.Results: The average age of the patients was 31 years (range 24–45).The tumor was on the left sided in 3 cases(60%) and right in 2 (40%).Tumor average size was 3.2 cm (rang 1–6).Histopathology detected thefollowing subtypes: mature teratoma in3 cases (60%), immature teratomain 1 (20%) and teratoma with malignanttransformation in (20%). Allpatients were at clinical stage I disease. Germ cell cancer microscopicmetastatic disease including embryonal carcinoma was detected in 1dissected lymph node of 1/4 patients (25%).Average follow up was 166months (range 93–249). All patients werealive and disease free and norelapses were detected during the follow up period.Conclusions: Primary pure teratoma of the testis does not respond tochemotherapy nor does it to radiation therapy. The disease treatmentoptions after orchidectomy for patients withclinical stage I disease includeRPLND or surveillance with their relativerisks and benefits. RPLND is thechosen treatment because it is both staging and treating. A close a longterm follow up is required since pure teratoma metastatic disease mayclinically develop after more than 10 years.     

The efficacy of 'Radio guided Occult Lesion Localization' (ROLL) versus 'Wire-guided Localization' (WGL) in breast conserving surgery for non-palpable breast cancer: A randomized clinical trial – ROLL study

Background

The gold standard for assessment of intraabdominal pressure (IAP) is via intravesicular pressure measurement (IVP). This accepted technique has some inherent problems, e.g. indirectness. Aim of this clinical study was to assess direct IAP measurement using an air-capsule method (ACM) regarding complications risks and agreement with IVP in patients undergoing abdominal surgery.

Methods

A prospective cohort study was performed in 30 patients undergoing elective colonic, hepatic, pancreatic and esophageal resection. For ACM a Probe 3 (Spiegelberg^®, Germany) was placed on the greater omentum. It was passed through the abdominal wall paralleling routine drainages. To compare ACM with IVP t-testing was performed and mean difference as well as limits of agreement were calculated.

Results

ACM did not lead to complications particularly with regard to organ lesion or surgical site infection. Mean insertion time of ACM was 4.4 days (min-max: 1–5 days). 168 pairwise measurements were made. Mean ACM value was 7.9 ± 2.7 mmHg while mean IVP was 8.4 ± 3.0 mmHg (n.s). Mean difference was 0.4 mmHg ± 2.2 mmHg. Limits of agreement were -4.1 mmHg to 5.1 mmHg.

Conclusion

Using ACM, direct IAP measurement is feasible and uncomplicated. Associated with relatively low pressure ranges (<17 mmHg), results are comparable to bladder pressure measurement.     

EUSOMA criteria for performing pre-operative MRI staging in candidates for breast conserving surgery: hype or helpful?

Ongoing debate regarding the value of pre-operative MRI in staging patients with newly diagnosed breast cancer has resulted from the lack of evidence on its clinical efficacy, which contrasts MRIs capability for detecting additional disease (occult on conventional imaging) in the cancerous breast. We undertook a validation study of EUSOMA criteria that recommend selection of breast conserving surgery (BCS) candidates to pre-operative MRI. We examined whether these criteria were associated with a differential likelihood of a recommendation for mastectomy. In a cohort of 200 subjects, recommended for BCS following mammography (M) and ultrasound (US), and who also subsequently had pre-operative MRI, the proportions recommended for mastectomy based on MRI, where the criterion was present versus absent were: invasive lobular cancer (17.9% versus 17.4%; p=0.87); high familial risk (14.7% versus 18.1%; p=0.82); M/US tumour size discrepancy >1cm (32.1% versus 15.1%; p=0.05); and for any of these criteria versus none (21.6% versus 14.3%; p=0.24). These findings suggest that EUSOMA criteria for selection to pre-operative MRI may be inefficient as they do not appear to differentiate those at risk of having more extensive disease and likely to receive a mastectomy recommendation, with the exception of M/US tumour size discrepancy.     

Laparoscopic one-stage resection of right and left colon complicated diverticulitis equivalent to hinchey stage I–II

Purpose  

The safety and effectiveness of laparoscopic surgery is well established for recurrent, uncomplicated diverticular disease, but not for complicated diverticular disease. Using the Hinchey classification, we compared laparoscopic colon resection (LAPH) with conventional open colon resection (OPH) for the treatment of complicated diverticulitis equivalent to Hinchey stage I–II.