Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Glomus Tumor of the Stomach: A Systematic Review and Illustrative Case Report.

INTRODUCTION: Glomus tumor (GT) is a rare mesenchymal neoplasm that can be found anywhere throughout the body, including the stomach. Our goal was to present a case and a systematic review of the literature, reporting clinical, radiological, surgical, and pathological features of the disease. METHODS: We reviewed Pubmed and SCOPUS for all case reports and case series published after 2000. Papers written in languages different from English and letters to the editor were excluded. Screening and data extraction were performed following the PRISMA guidelines. RESULTS: A total of 89 studies were included in the systematic review, consisting of 187 cases of gastric glomus tumor. Mean age was 52 (18-90); most patients were female (61%). The most common clinical presentation was epigastric pain (33.9% of cases). The gastric antrum was the most frequently involved site (75.3%). Mean tumor size was 2.82 cm (0.8-17). Preoperative diagnosis was achieved in 22 cases, mostly by endoscopic ultrasound (EUS)-guided biopsy. Wedge resection was performed in 62% of treated patients. Smooth muscle actin was expressed in all cases with available immunohistochemistry. Malignant GT was reported in 11 cases. DISCUSSION: Epigastric pain and bleeding were the most common symptoms at presentation in patients with diagnosis of glomus tumor. EUS-guided fine needle aspiration can be useful for preoperative diagnosis. Endoscopic elastosonography is a promising tool for the differential diagnosis of gastric submucosal lesions, including glomus tumors. The treatment of choice is wedge resection with adequate free margins. A laparoscopic approach is warranted when technically feasible. Since malignant gastric GTs have been described, long-term follow-up is suggested after surgical excision.

Preoperative monocyte-to-lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors.

BACKGROUND AND OBJECTIVES: Several inflammation markers were found to have a prognostic value in cancer. We investigated the significance of preoperative white cell ratios in determining gastrointestinal stromal tumors (GISTs) outcome. METHODS: Clinicopathological features of patients who underwent surgery for GIST were reviewed. The following peripheral blood inflammation markers were calculated: neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-white blood cell ratio (NWR), lymphocyte-white cell ratio (LWR), monocyte-white cell ratio (MWR), and platelet-white cell ratio (PWR). RESULTS: We analyzed 127 patients. Three- and five-year disease-free survival (DFS) were 89.7% and 86.9%, respectively. The univariate analysis selected tumor diameter (P = 0.003), gastric location ( P = 0.024), cell type ( P = 0.024), mitosis ( P < 0.001), MLR ( P = 0.014), NLR ( P = 0.016), and PLR ( P = 0.001) as the factors associated to DFS. The independent prognostic factors for DFS were mitosis ( P = 0.001), NLR ( P = 0.015), MLR ( P = 0.015), and PLR ( P = 0.031), with MLR showing the highest statistical significance and hazard ratio (HR) value. MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinen's risk class. A high value of MLR was associated with reduced DFS. CONCLUSION: MLR, NLR, and PLR are independent prognostic factors for DFS in GISTs. We first demonstrated the role of MLR as a predictor of recurrence in GIST. Its inclusion into clinical management may improve the recurrence estimation.

Role of surgery in the multimodal treatment of primary and recurrent leiomyosarcoma of the inferior vena cava.

BACKGROUND: The optimal treatment of leiomyosarcoma (LMS) of the inferior vena cava (IVC) is still unclear, especially in the metastatic and/or recurrent setting. We herein evaluated the long-term outcome after aggressive management. METHODS: Eleven patients underwent surgery for primary LMS of the IVC between 2000 and 2012. The clinical, pathological, and survival data were reviewed. RESULTS: The IVC was managed by graft replacement in four cases, primary repair in four, and ligation in three. The R0 resection rate was 64%. The median follow-up was 60 months. Nine patients developed distant relapse, two of them concomitant local recurrence; no exclusive local recurrence was observed. The 3- and 5-year distant recurrence free survival were 30% and 10%, respectively. The 3- and 5-year overall-survival (OS) were 77.8%. The presence of residual disease after surgery (P = 0.024) and the time to recurrence (P = 0.033) were associated with the OS in a univariate analysis. The time to recurrence was related to the post-metastases survival (P = 0.032). CONCLUSIONS: An adequate surgery minimizes the risk of local recurrence and remains the main treatment for primary LMS of the IVC. Nevertheless, the rate of distant metastases remains extremely high. An aggressive surgical policy may be of benefit to selected patients with metastatic disease. J. Surg. Oncol. 2016;114:44-49. © 2016 Wiley Periodicals, Inc.

Prognostic value of mitotic count in leiomyosarcoma: A comprehensive monocentric retrospective study.

BACKGROUND: Leiomyosarcomas (LMSs) include heterogeneous entities with different clinical courses not entirely predicted by known prognostic factors. In particular, the value of mitotic count as independent prognostic factor in LMS has been poorly investigated. METHODS: We retrospectively analyzed all patients with a diagnosis of LMS who accessed to our Institution from June 1999 to May 2022 for which mitotic count was numerically expressed within the pathology report. Univariate and multivariate analyses were conducted to explore the prognostic value of mitotic count along with other clinical and histological variables. RESULTS: We identified 121 eligible patients, with a median follow-up of 91.03 months (range 0.62-275.2 months). Median progression-free survival (mPFS) was 16.7 months, and median overall survival (mOS) was 105.6 months. In univariate analysis, mitotic count showed a significant impact on PFS and OS, with an hazard ratio per mitotic unit of 1.03 (1.01-1.04, p < 0.001) and 1.03 (1.01-1.04, p = 0.007), respectively. Similar results were found for locally advanced and metastatic patients, separately. Other significant prognostic factors for PFS were stage at diagnosis, performance status, tumor size and Ki-67, while differentiation, necrosis, grade, stage at diagnosis, tumor size, performance status and age at diagnosis were identified for OS. In multivariate analysis, the only significant factors were mitotic count and the presence of metastases at diagnosis for PFS, whereas the same two factors plus age at diagnosis were identified for OS. CONCLUSION: Mitotic count represented the most important histological prognostic factor for OS and PFS in localized and metastatic LMS.

Exploring the CXCR4/CXCR7/CXCL12 Axis in Primary Desmoid Tumors.

BACKGROUND: Desmoid tumors have an extremely variable natural history. The uncertainty behind desmoid behavior reflects the complexity, which subtends its development and non-linear advancement. Apart from Wnt- ßcatenin mutation, estrogen receptors, and COX-2 overexpression, little is known about the ability of desmoids to grow and recur while being unable to metastasize. Several tumors have been shown to express the CXCR4/CXCR7/CXCL12 axis, whose functions are essential for tumoral development. AIMS: This study aimed to investigate the expression of the CXCR4/CXCR7/CXCL12 axis in primary desmoid tumors and discuss the potential role of this key-signaling as an antiangiogenic therapeutic strategy. METHODS: In this study, 3 µm-thick consecutive sections from each formalin-fixed and paraffin-embedded tissue block were treated with mouse monoclonal antibodies developed against CD34, CXCR4, CXCR7, and CXCL12. RESULTS: Two distinct vessel populations: CXCR4+ and CXCR4- vessels, have been found. Similarly, chemokine receptor CXCR7 expression in the entire desmoid tumor series positively stained a portion of tumor-associated vessels, identifying two distinct subpopulations of vessels: CXCR7+ and CXCR7- vessels. All 8 neoplastic tissue samples expressed CXCL12. Immunohistochemical positivity was identified in both stromal and endothelial vascular cells. Compared to CXCR4 and CXCR7, the vast majority of tumor-associated vessels were found to express this chemokine. CONCLUSION: It is the first time, as per our knowledge, that CXCR4/CXCR7/CXCL12 axis expression has been identified in a desmoid type-fibromatosis series. CXCL12 expression by neoplastic cells, together with CXCR4 and CXCR7 expression by a subgroup of tumor-associated vessels, was detected in all desmoid tumor tissue samples examined. Since chemokines are known contributors to neovascularization, CXCR4/CXCR7/CXCL12 axis may play a role in angiogenesis in this soft-tissue tumor histotype, thereby supporting its growth.

Optimal Predictors of Postoperative Complications After Gastrectomy: Results from the Procalcitonin and C-reactive Protein for the Early Diagnosis of Anastomotic Leakage in Esophagogastric Surgery (PEDALES) Study.

BACKGROUND: The aim of this study was to define whether procalcitonin (PCT) is an earlier and more accurate predictor than C-reactive protein (CRP) for anastomotic leakage (AL) and major infective complications (MICs). METHODS: This was a prospective multicentric observational study conducted in three Italian centers, including all patients undergoing gastrectomy from May 2016 to April 2021. The endpoint was the assessment of the discrimination and accuracy achieved by the PCT and CRP values measured from POD1 to POD7 for predicting the occurrence of AL and MICs. Accuracy was assessed by calculating the area under the receiver operating curve (AUROC) values and Youden's statistics. Two charts were created for risk stratification during the postoperative course. RESULTS: The rate of AL was 4.6%, with a median day of occurrence on POD5 (range 3-26). The overall rate of major infective complications was 19.9%, with a median day of occurrence on POD6 (range 2-30). PCT showed a significant association with AL on POD6 and POD7 and a significant association with MICs on POD2, while CRP values showed a significant association with AL on POD4 and a significant association with MICs on POD1. No difference in the prediction of AL was observed between PCT and CRP, while CRP was found to be a superior predictor of major infective complications on POD5 (p = 0.024) and POD7 (p = 0.035). CONCLUSIONS: PCT was not superior to CRP as an early predictor of AL and major infective complications after gastrectomy. CRP should be used as the reference screening postoperative marker.

Prophylactic Ureteral Catheter Placement Appears to Reduce Intraoperative Ureteric Injury During Resection of Primary Retroperitoneal Liposarcoma.

Background: Prophylactic ureteral catheters placement (PUCP) was advocated as an effective strategy for decreasing ureteral morbidities in colorectal surgeries. However, whether it should be routinely used prior to primary retroperitoneal liposarcoma (PRLS) surgeries remains unknown. Methods: It was a retrospective study, conducted at a tertiary sarcoma center. Medical records of patients with PRLS undergoing surgeries from January 2015 through December 2018 were reviewed. Primary endpoint was the rate of ureteral morbidities during and after retroperitoneal liposarcoma resection procedures. Univariate and multivariate analyses determined risk factors associated with ureteral injury (UI) in patients undergoing surgeries. Results: A total of 55 patients of PRLS were included. Fourteen (25.5%) patients underwent PUCP, with 1 UI (7.1%) identified. In 41 patients with no PUCP, 15 (36.6%) exhibited UIs during and post surgeries. There were significant improvements of UIs in group PUCP, compared with patients without PUCP (P < .05). Resection surgeries combined with colectomy and tumor-ureter relationship were 2 risk factors significantly associated to UIs (P < .01). Conclusions: PUCP might be an effective way of preventing UIs in patients with PRLS. It could be suggested especially in patients with ureter encased by tumor or anticipated colectomy during the surgical process.

Measuring the impact of complications after surgery for retroperitoneal sarcoma: Is comprehensive complication index better than Clavien-Dindo Classification?

BACKGROUND: To compare the Clavien-Dindo classification (CDC) and the Comprehensive Complication Index (CCI) in retroperitoneal sarcoma (RPS) surgery in assessing the real burden of post-operative complications on both post-operative length of stay and total costs of hospitalization (PLOS and TCH, respectively). STUDY DESIGN: A series of 417 procedures for both primary and recurrent RPS between January 2000 and December 2017 was analyzed. Complications were classified according to both CDC and CCI. Univariable linear regressions were used to assess predictors associated with PLOS and TCH. Multivariable linear regression models were constructed to identify the factors independently associated with PLOS and TCH. RESULTS: Median PLOS was 10 days (interquartile range [IQR] 7-16); median TCH was 7033.5€ (IQR 1350-305.900). Post-operative complications occurred in 170/417 (40.7%) of the procedures and in 75/417 (17.9%) of the procedures CDCs >3 were identified. Sixty-four (15.34%) patients had more than one complication. Univariable linear regression showed that both PLOS and TCH were significantly associated to both CDC and CCI among other factors. Multivariable linear analyses selected CDC and CCI as independent prognostic factors for both PLOS and TCH. According to the AIC and BIC, models including CCI performed better (5559.53 and 5598.18, respectively, compared with 5561.31 and 5599.95 for CDC models). CONCLUSION: The CCI resulted to perform better than the CDC in describing the overall burden of complications after RPS surgery, both for clinical and economic purposes.

Major vascular resection in retroperitoneal sarcoma surgery.

Major blood vessels may be invaded either by primary sarcomas arising from the vessel wall or by secondary infiltration of a retroperitoneal sarcoma. The involvement of major blood vessels is not considered to be an absolute contraindication for surgical resection. The main issue when evaluating a possible major vascular resection is to balance the possible surgical morbidity with the expected survival benefit. This is strictly related to the tumor's biology and clinical behavior and to the patient's performance status and comorbidities. A multidisciplinary approach in a specialized center is mandatory when approaching a possible oncovascular resection for retroperitoneal sarcoma, given the rarity and the heterogeneity of these tumors.

Event-free survival in Desmoid-Type fibromatosis (DTF): A pre-post comparison of upfront surgery versus wait-and-see approach.

BACKGROUND: Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF. METHODS: We analyzed 87 consecutive patients with histologically-proven sporadic primary DTF, first recurrence or residual disease managed at our institution between 2000 and 2018. Patients and tumor-related variables were reviewed and analyzed. Two different treatment strategies were adopted according to different time periods: in the "early period" (2000-2010) patients underwent surgical treatment irrespective of the clinical presentation, whereas in the "late period" (2012-2018) asymptomatic patients used to undergo a wait-and-see strategy. The event-free survival (EFS) was compared trough a pre-post comparison. RESULTS: In the early period, surgery was performed in 51 (94.4%) patients and watchful waiting in 3 (5.6%). In the late period, the watchful waiting group accounted for 24 (72.7%) patients and the surgical group for 9 (27.3%). No statistically independent prognostic factors were found. EFS did not show statistically significant differences between early and late period groups. CONCLUSION: Wait-and-see policy has shown to be equivalent to upfront surgery in terms of EFS; therefore, a conservative approach is recommended in asymptomatic patients diagnosed with DTF that can be followed through watchful waiting.

Adoption of a Newly Introduced Dermal Matrix: Preliminary Experience and Future Directions.

INTRODUCTION: Acellular dermal matrix (ADM) products are adopted in the management of injuries to soft tissues. ADMs have been increasingly employed for their clinical advantages, and they are acquiring relevance in the future of plastic surgery. The aim of our study is to evaluate the application of ADMs in our patients who could not undergo fast reconstruction. MATERIALS AND METHODS: We performed a retrospective study on 12 patients who underwent ADM placement for scalp and limb surgical reconstructions at the Humanitas Research Hospital, Rozzano (Milano), Italy. Wounds resulted from 9 tumor resections and 3 chronic ulcers. The ADM substrate used to treat these lesions was PELNAC™ (Gunze, Japan), a double-layered matrix composed of atelocollagen porcine tendon and silicon reinforcement. All patients underwent a second surgical operation to complete the treatment with a full-thickness skin graft to cover the lesion. RESULTS: In this study, 12 patients were treated with PELNAC™: 11 out of 12 patients showed a good attachment over a median time of 21.3 days (range 14-27). After almost 23 days, all patients were ready to undergo a full-thickness skin grafting. CONCLUSION: This study assesses the benefits of PELNAC™ and proposes this method as an alternative to traditional approaches, especially in situations where the latter techniques cannot be applied.

Multimodality imaging of adult rhabdomyosarcoma: the added value of hybrid imaging.

Rhabdomyosarcoma (RMS) represents more than 50% of paediatric soft tissue tumours. Conversely, it is extremely rare among adults, where it shows peculiar biological and clinical features that are still poorly investigated. RMS patients should be referred to a Sarcoma Centre, where the contribution of experienced radiologists plays a relevant role in the diagnostic assessment of the disease, including precise localisation, staging, image-guided biopsy, response evaluation after treatment and follow-up. Besides CT and MRI, hybrid imaging including positron emission tomography (PET)/CT and PET/MRI are giving an increasing contribution to provide functional insights about tumour biology and to improve the diagnostic accuracy of the imaging work-up. This review paper provides a revision of the pathology, clinical and radiological features of adult RMS, with a particular focus on the growing role of hybrid PET-based imaging.

How Should We Measure the Quality of Lymphadenectomy for Gastric Cancer? Anatomical Versus Numerical Criterion.

AIM: To compare anatomical with numerical criterion to measure the quality of lymphadenectomy for gastric cancer. PATIENTS AND METHODS: We analyzed 447 gastric cancer patients with resectable tumor stage (R0 resection) with at least 16 examined lymph nodes. RESULTS: Of 447 patients, 82.6% underwent D2 lymphadenectomy for a median of total examined lymph nodes of 28. The 7-year disease-specific survival rate for the whole sample was 71.4%. Survival was significantly different between patients treated with D2 and D1 lymphadenectomy (77.4% versus 44.3%; p < 0.001) and between patients with total examined lymph nodes ≥ 28 and < 28 (74.5% versus 62.3%; p = 0.041). Anatomical criterion significantly differentiated 7-year survival in patients stratified according to a numerical parameter. CONCLUSION: We should still consider the anatomical criterion as the best item to measure the quality of lymphadenectomy for gastric cancer.

Italian consensus conference on management of uterine sarcomas on behalf of S.I.G.O. (Societa' italiana di Ginecologia E Ostetricia).

BACKGROUND: Uterine sarcomas are very rare tumours with different histotypes, molecular features and clinical outcomes; therefore, it is difficult to carry out prospective clinical trials, and this often results in heterogeneous management of patients in the clinical practice. AIM: We planned to set up an Italian consensus conference on these diseases in order to provide recommendations on treatments and quality of care in our country. RESULTS: Early-stage uterine sarcomas are managed by hysterectomy + bilateral salpingo-oophorectomy according to menopausal status and histology; lymphadenectomy is not indicated in patients without bulky nodes, and morcellation must be avoided. The postoperative management is represented by observation, even though chemotherapy can be considered in some high-risk patients. In early-stage low-grade endometrial stromal sarcoma and adenosarcomas without sarcomatous overgrowth, hormonal adjuvant treatment can be offered based on hormone receptor expression. In selected cases, external beam radiotherapy ± brachytherapy can be considered to increase local control only. Patients with advanced disease involving the abdomen can be offered primary chemotherapy (or hormonal therapy in the case of low-grade endometrial stromal sarcoma and adenosarcoma without sarcomatous overgrowth), even if potentially resectable in the absence of residual disease in order to test the chemosensitivity (or hormonosensitivity); debulking surgery can be considered in patients with clinical and radiological response. Chemotherapy is based on anthracyclines ± ifosfamide or dacarbazine. Palliative radiotherapy can be offered for symptom control, and stereotactic radiotherapy can be used for up to five isolated metastatic lesions. CONCLUSIONS: Treatment of uterine sarcoma should be centralised at referral centres and managed in a multidisciplinary setting.

Did outcomes improve in retroperitoneal sarcoma surgery?

In the last decades, the deeper understanding of the biological basis of the disease, along with the advances of surgical techniques and oncologic multimodal treatments, have led to an overall increase of survival of cancer patients. However, significant amelioration of the prognosis of rare and under-investigated tumors such as soft tissue sarcoma is less evident. In this review, main changes in the surgical management of retroperitoneal sarcoma (RPS) are discussed in order to figure out whether actual improvement in RPS outcome has been occurred in the last years.

Short-term outcomes after duodenal surgery for mesenchymal tumors: a retrospective analysis from a single tertiary referral center.

Duodenal resections are sometimes necessary for radical surgery. We analyzed technical aspects and post-operative outcomes in patients with RPS and GIST involving duodenum. We identified patients who underwent duodenal resection for RPS and GIST at our Institute between 2000 and 2016. Clinical, pathological and treatment variables were analyzed. Thirty patients were treated: 15 for GIST, 15 for RPS. Sixteen duodenal wedge resections (WR) and 14 segmental resections (SR) were performed. Multi-organ resection was frequently performed (63.4%). Median time to flatus was 3 days (range 1-6), to oral refeeding 4.5 (range 2-15). Overall postoperative morbidity rate was 53% (16/30): Clavien Dindo grade ≤ II: 10; duodenum-related complication rate was 33% (10/30), Clavien Dindo grade ≤ II: 9. Morbidity rates were higher in SR than WR. Duodenal resections for RPS and GIST have significant morbidity rate and whenever it is possible, WR is preferable to SR because of the lower morbidity rate.