Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).

BACKGROUND: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking. METHODS: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011. Uni- and multivariable logistic models were fitted to study the association between major (Clavien-Dindo grade ≥ 3) complications and patient/surgery characteristics as well as outcome. The resected organ score, a method of standardizing the number of organs resected, as previously described by the TARPSWG, was used. RESULTS: The 681 patients in this study had a median age of 59 years, and 51.8% were female. The most common histologic subtype was de-differentiated liposarcoma (43%), the median resected organ score was 1, and 83.3% of the patients achieved an R0 or R1 resection. Major complications occurred for 16% of the patients, and the 90-day mortality rate was 0.4%. In the multivariable analysis, a transfusion requirement was found to be a significant predictor of major complications (p < 0.001) and worse overall survival (OS) (p = 0.010). However, having a major complication was not associated with a worse OS or a higher incidence of local recurrence or distant metastasis. CONCLUSIONS: A surgical approach to recurrent RPS is relatively safe and comparable with primary RPS in terms of complications and postoperative mortality when performed at specialized sarcoma centers. Because alternative effective therapies still are lacking, when indicated, resection of a recurrent RPS is a reasonable option. Every effort should be made to minimize the need for blood transfusions.

Analysis of Differentiation Changes and Outcomes at Time of First Recurrence of Retroperitoneal Liposarcoma by Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

BACKGROUND: Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differentiated (WD) and dedifferentiated (DD) RLPS are distinct entities with differing outcomes. A few reports suggest that WDLPS can recur as DDLPS and that DDLPS can recur as WDLPS. This study evaluates whether this change in differentiation from the primary tumor to the first local recurrence impacts long-term outcomes. METHODS: Retrospective review from 22 sarcoma centers identified consecutive patients who underwent resection for a first locally recurrent RLPS from January 2002 to December 2011. Outcomes measured included overall survival, local recurrence, and distant metastasis. RESULTS: A total of 421 RPLS patients were identified. Of the 230 patients with primary DDLPS, 34 (15%) presented WDLPS upon recurrence (DD → WD); and of the 191 patients with primary WDLPS, 54 (28%) presented DDLPS upon recurrence (WD → DD). The 6-year overall survival probabilities (95% CI) for DD → DD, DD → WD, WD → WD, and WD → DD were 40% (32-48%), 73% (58-92%), 76% (68-85%), and 56% (43-73%) (p < 0.001), respectively. The 6-year second local recurrence incidence was 66% (59-73%), 63% (48-82%), 66% (57-76%), and 77% (66-90%), respectively. The 6-year distant metastasis incidence was 13% (9-19%), 3% (0.4-22%), 5% (2-11%), and 4% (1-16%), respectively. On multivariable analysis, DD → WD was associated with improved overall survival when compared with DD → DD (p < 0.001). Moreover, WD → DD was associated with a higher risk of LR (p = 0.025) CONCLUSION: A change in RLPS differentiation from primary tumor to first local recurrence appears to impact survival. These findings may be useful in counseling patients on their prognosis and subsequent management.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Clinicopathologic Characteristics and Prognosis of Invasive Papillary Carcinoma of the Breast.

BACKGROUND: Invasive papillary carcinoma (IPC) of the breast is thought to carry a more favorable prognosis than invasive ductal carcinoma (IDC). The aim of this study is to investigate the clinicopathological characteristics between IPC and IDC and their prognosis using a large nationwide data set. METHODS: Female patients diagnosed with malignant IPC and IDC between 2005 and 2014 were analyzed. Patients with incomplete survival data, stage 0/IV, unknown stage, or recurrent disease were excluded. Five-year overall survival was compared between IPC and IDC. RESULTS: Among 308,426 patients, 1147 had IPC and 307,279 had IDC. IPC presented more in older postmenopausal women, black Americans, and people who had government insurance. IPC had larger tumor size, lower-grade, and earlier-stage disease, less node-positive disease, higher hormone positivity, and lower human epidermal growth factor receptor 2 amplification. Adjuvant radiation and chemotherapy rates were lower in IPC than those in IDC. IPC had a similar 5-year overall survival as compared with IDC overall (86.8% versus 88.7%) (P = 0.06). Age, pathologic stage, and radiation treatment were shown to be independent prognostic factors of IPC. CONCLUSIONS: IPC has a similar prognosis as IDC, suggesting that these patients should follow the same treatment protocols.

Primary mesenteric sarcomas: Collaborative experience from the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

BACKGROUND: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function. OBJECTIVES: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS. METHODS: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019. RESULTS: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery. CONCLUSION: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging.

Outcomes of patients with invasive mucinous and tubular carcinomas of the breast.

Invasive tubular carcinoma (ITC) and invasive mucinous carcinoma (IMC) of the breast are rare histologic subtypes of breast cancer associated with favorable prognoses. The aim of our study was to investigate the outcomes for these rare subtypes using the National Cancer Database. Female patients diagnosed with ITC or IMC between 2005 and 2014 were analyzed. The primary outcome was overall survival (OS), and we analyzed its association with adjuvant therapy. 2735 patients with ITC and 5602 patients with IMC were identified. ITC presented in younger patients (57 vs. 67 years), had smaller tumors (size <1 cm, 63.1% vs. 25.4%), earlier stage, and less node-positive disease (5% vs. 8.6%), compared with IMC. Older age, government insurance, lower income, treatment in a community cancer program, large tumor size, positive nodal status, and without endocrine therapy were associated with worse OS with either subtype on multivariate analysis. No OS benefit was found for node-positive ITC that received adjuvant chemotherapy compared with those who did not. (5-year OS of 96.0% vs. 91.3%, p = 0.17).OS was improved for IMC that received adjuvant chemotherapy (10-year OS: 82.5% vs. 60.1%, p = 0.008) and endocrine therapy (10-year OS: 86.6% vs. 81.2%, p < 0.001). We concluded that ITC has favorable clinicopathological characteristics and prognosis, even with node-positive disease. ITC and IMC may need to be evaluated independently when administering adjuvant treatment plans.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Completion lymph node dissection in patients with sentinel lymph node positive cutaneous head and neck melanoma.

BACKGROUND: Relatively few cutaneous head and neck melanoma (CHNM) patients with were included in the multicenter selective lymphadenectomy trial II (MSLT-II). Our objective was to investigate whether immediate completion lymph node dissection completion of lymph node dissection (CLND) was associated with survival benefit for sentinel lymph node (SLN) positive CHNM using the National Cancer Database. METHODS: SLN positive patients with CHNM from 2012 to 2014 were retrospectively analyzed. Patients were divided into two groups: those who underwent SLN biopsy (SLNB) only versus those who underwent SLNB followed by CLND (SLNB + CLND). The primary outcome was 5-year overall survival (OS). RESULTS: Among 530 SLNB + patients, 342 patients underwent SLNB followed by CLND (SLNB + CLND). The SLNB only group had fewer positive SLN, less advanced pathologic stage, and a lower rate of adjuvant immunotherapy. There was no significant difference in 5-year OS between the two groups (51.0% vs 67%; P = .56). After adjusting for pathologic stage, there remained no difference in 5-year OS among patients with stage IIIA (63.0% vs. 73.6%, P = 0.22) or IIIB/IIIC disease (39.1% vs 57.8%; P = .52). Conclusions Using a large nationwide database, CLND was not shown to be associated with improved OS for patients with SLNB positive CHNM, validating the results of MSLT-II.

Clinical significance of SLN benign capsular nevi in patients with melanoma.

BACKGROUND: Benign capsular nevi (BCN) are not infrequent in sentinel lymph nodes (SLN) of patients with melanoma. Their prognostic significance is unknown and the literature is limited. This study evaluated the clinical significance of incidentally found BCN in these patients. METHODS: A multi-institutional retrospective review of patients undergoing SLN biopsy for cutaneous melanoma between 2000 and 2016. Patients were divided into the following groups: (a) negative SLN and no BCN, (b) negative SLN and presence of BCN, (c) positive SLN seen only on immunohistochemistry (IHC), and (d) positive SLN via hematoxylin and eosin (H&E). Outcomes measured were overall survival and any recurrence. RESULTS: A total of 1253 patients were identified (group 1 = 978, group 2 = 56, group 3 = 32, and group 4 = 187). Fifty-seven percent were male and the mean age was 59.3 years. BCN was identified in 77 patients (6.2%), of which the majority was in the node-negative group (72%). Multivariable analysis showed that BCN was associated with lower recurrence rates, though not statistically significant (hazard ratio [HR] = 0.5; P = .06). IHC- and H&E-positive SLNs were associated with a higher risk of recurrence (HR = 2.4; P = .02 and 2.0, P < .0001, respectively). CONCLUSION: Patients with BCN and negative SLN had lower recurrence rates than patients with negative SLN and no BCN. Our data suggest a possible protective effect against recurrence.

Trends in utilization of sentinel node biopsy and adjuvant radiation in women ≥ 70.

BACKGROUND AND OBJECTIVES: Omission of routine axillary staging and adjuvant radiation (XRT) in women ≥ 70 years old with early stage, hormone receptor-positive, clinically node-negative breast cancer has been endorsed based on several landmark studies. We sought to determine how much omission of axillary staging/XRT has been adopted. METHODS: Using the National Cancer Data Base, we selected malignant breast cancer cases in women ≥ 70 with ER + tumors, ≤2 cm with clinically negative lymph nodes who underwent breast conservation and had known XRT status in 2005-2015. The use of sentinel lymph node biopsy (SNB) and XRT status was summarized by year to determine trends over time. RESULTS: In total, 57 230/69 982 patients underwent SNB. Of the 12 752 patients in whom SNB was omitted, 6296 were treated at comprehensive community cancer programs. Regarding XRT, 33 891/70 114 received adjuvant XRT. There were no significant trends with regards to patients receiving SNB or those receiving XRT. CONCLUSION: Since 2005, there has been no change in SNB or XRT for early stage ER + breast tumors. However, there was a difference in omission of SNB based on facility type and setting. Future monitoring is needed to determine if these trends persist following the recently released Choosing Wisely® recommendations.

Sexual dimorphism in the incidence of human cancers.

BACKGROUND: Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers. METHODS: We analyzed four sets of cancer incidence data from the SEER (USA, 1975-2015), from the Cancer Registry at Mayo Clinic (1970-2015), from Sweden (1970-2015), and from the World Cancer Report in 2012. RESULTS: We found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant. CONCLUSIONS: Sexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.

Intraoperative fluid restriction in hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Multiple studies highlight the importance of liberal fluid administration in cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Over-resuscitation can delay recovery and wound healing. We report an intraoperative protocol that restricts fluid administration and minimizes morbidity. MATERIALS AND METHODS: Retrospective analysis of 35 patients that underwent CRS-HIPEC for curative intent under fluid restriction protocol from June 2015 to July 2017 was performed. Protocol consists of continuous infusion of vasopressin 0.02 units/h and maintaining urine output at 0.5 mL/kg/h via crystalloid and colloid. Endpoint was Clavien-Dindo ≥3 events within 30 d of CRS-HIPEC. RESULTS: Median age was 56 y; 71% were female. Malignancies treated: appendix (49%), colon (31%), and other (20%). Median peritoneal cancer index was 15, complete cytoreduction was achieved in 91% of patients. Median time for return of bowel function was 5 d, median length of hospital stay was 7 d. There were 28 bowel anastomoses. Median intraoperative crystalloid, colloid, and packed red blood cells were (1900, 1500, and 700 mL), respectively. Clavien-Dindo grade 3-4 events occurred in five patients. There were no deaths 30 d after surgery. CONCLUSIONS: A fluid restriction protocol appears to be safe and feasible in the setting of CRS-HIPEC for curative intent.

Multiply recurrent retroperitoneal liposarcoma.

Retroperitoneal liposarcomas (RPLPS) are rare tumors that represent at least 50% of all retroperitoneal sarcomas. Surgical resection remains the standard of care. Unfortunately, many RPLPS patients will develop a local recurrence and subsequently die in the absence of distant metastasis. This review outlines the factors that predict local recurrence and influence the management of first and subsequent multiply recurrent RPLPS.

Effect of nephrectomy for retroperitoneal sarcoma on post-operative renal function.

BACKGROUND AND OBJECTIVES: Surgical resection of retroperitoneal sarcomas (RPS) often involves removal of the ipsilateral kidney. We evaluated the long-term post-operative renal function in patients who underwent a nephrectomy as part of their en-bloc resection of RPS. METHODS: Retrospective review of an institutional database identified RPS patients who underwent nephrectomy for curative intent from 1990 to 2014. The primary outcome measured was chronic kidney disease (CKD) calculated by the glomerular filtration rate (GFR). RESULTS: Of the 47 patients in our study, 19 (40%), 18 (38%), and 10 (21%) patients had a preoperative CKD stage 1, 2, and 3, respectively. The GFR decreased by an average of 33.4 mL/min/1.73 m2 with 66% of patients demonstrating mild progression of their renal impairment. Only three (6%) patients progressed to CKD stage 4 or 5, one of which required life-long dialysis. CONCLUSION: Nephrectomy as part of an en-bloc resection is associated with a decrease in GFR that is not clinically significant. Fear of kidney failure should not prevent a surgeon from performing a nephrectomy in the treatment of RPS.

The Influence of Breast Density on Preoperative MRI Findings and Outcome in Patients with a Known Diagnosis of Breast Cancer.

BACKGROUND: The role of breast density as an indication for preoperative breast magnetic resonance imaging (MRI) for surgical planning in women with breast cancer is unknown. METHODS: We retrospectively reviewed breast cancer patients diagnosed from 2007 to 2011 who underwent preoperative MRI. We obtained clinical and pathological data and grouped patients by mammographic breast density, with Breast Imaging Reporting and Data System (BI-RADS) density A and B considered low density, and C and D considered high density. We analyzed local recurrence rates by breast density. RESULTS: Among 683 patients, 66.6% had high breast density. We noted MRI abnormalities in the ipsilateral breast in 41.8% high-density and 30.7% low-density breasts, while contralateral abnormalities were noted in 24.9% high-density and 13.8% low-density breasts. Biopsy was recommended for MRI findings in a similar number of patients regardless of density cohort. While more abnormalities were found in high-density breasts, the rate of additional cancer found was not significantly different (ipsilateral: 32 vs. 23%; contralateral: 6.2 vs. 3.2%) for high-and low-density patients, respectively (both p > 0.15). With a median follow-up of 89 months, and similar rates of adjuvant systemic and radiation therapy, no difference in local recurrence rates existed when stratified according to density classification (p > 0.53). CONCLUSION: While more abnormalities were identified on MRI in dense breasts, there was no statistically significant difference in the number of cancers identified or in recurrence rates. These findings question the routine use of preoperative breast MRI in women with newly diagnosed breast cancer based solely on breast density.

Trends in Sexual Function After Breast Cancer Surgery.

PURPOSE: Sexual dysfunction is assumed to be common, but understudied, in breast cancer patients. Herein, we use the validated female sexual functioning index (FSFI) to evaluate changes in female sexual function after breast cancer surgery. METHODS: The FSFI assesses sexual function in six domains (desire, arousal, lubrication, orgasm, satisfaction, pain) on a 36-point scale, with scores >26.6 indicating better sexual function. We identified 226 women with unilateral breast cancer undergoing surgery at our institution from June 2010-January 2015. All completed the FSFI preoperatively and at a median of 13 months postoperatively. We quantified declines in FSFI scores and considered p-values <0.05 statistically significant. RESULTS: Overall, 119 women had breast-conserving surgery (BCS), 40 had unilateral mastectomy (UM), and 67 had UM plus contralateral prophylactic mastectomy (CPM). All women had similar baseline FSFI scores (medians: BCS, 26.3; UM, 25.2; UM+CPM, 23.7; p = 0.23). At follow-up, sexual function had declined significantly in BCS (23.5; p < 0.001) and UM (17.4; p = 0.010), but was unchanged in UM+CPM (22.8; p = 0.74) women. Interestingly, all women maintained their desire for sex (p = 0.17). BCS and UM women demonstrated significant declines in all other subscale domains (all p < 0.045). UM+CPM women demonstrated no decline in any subscale domain, yet did not exhibit superior sexual function to those having UM or BCS (medians: BCS, 23.5; UM, 17.4; UM+CPM, 22.8; p = 0.21). CONCLUSIONS: Baseline sexual dysfunction exists in women diagnosed with breast cancer. Surgery negatively impacts sexual function. Patients who choose mastectomy do not exhibit superior sexual function over those having BCS at 13 months following surgery.