Disruptions in antigen processing and presentation machinery on sarcoma.

BACKGROUND: The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients. METHODS: We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001-2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used. RESULTS: All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit ß2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS. CONCLUSION: Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit ß2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

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.

Prognostic Indicators in Stage IV Surgically Treated Gastric Cancer Patients: A Retrospective Multi-Institutional Study.

INTRODUCTION: The role of gastric resection in treating metastatic gastric adenocarcinoma is controversial. In the present study, we reviewed the short- and long-term outcomes of stage IV patients undergoing surgery. METHODS: A retrospective review was conducted that assessed patients undergoing elective surgery for incurable gastric carcinoma. Short- and long-term results were evaluated. RESULTS: A total of 122 stage IV gastric cancer patients were assessed. Postoperative mortality was 5.7%, and the overall rate of complications was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19% respectively; the median survival was 14 months. Improved survival was observed for the factors age less than 60 years (p = 0.015), site of metastases (p = 0.022), extended lymph node dissection (p = 0.044), absence of residual disease after surgery (p = 0.001), and administration of adjuvant chemotherapy (p = 0.016). Multivariate analysis showed that residual disease and adjuvant chemotherapy were independent prognostic factors. CONCLUSIONS: The results of this study suggest that surgery combined with systemic chemotherapy in selected patients with stage IV gastric cancer can improve survival.

Total vs proximal gastrectomy for adenocarcinoma of the upper third of the stomach: a propensity-score-matched analysis of a multicenter western experience (On behalf of the Italian Research Group for Gastric Cancer-GIRCG).

BACKGROUND: The aim of this study is to compare surgical outcomes including postoperative complications and prognosis between total gastrectomy (TG) and proximal gastrectomy (PG) for proximal gastric cancer (GC). Propensity-score-matching analysis was performed to overcome patient selection bias between the two surgical techniques. METHODS: Among 457 patients who were diagnosed with GC between January 1990 and December 2010 from four Italian institutions, 91 underwent PG and 366 underwent TG. Clinicopathologic features, postoperative complications, and survivals were reviewed and compared between these two groups retrospectively. RESULTS: After propensity-score matching had been done, 150 patients (75 TG patients, 75 PG patients) were included in the analysis. The PG group had smaller tumors, shorter resection margins, and smaller numbers of retrieved lymph nodes than the TG group. N stages and 5-year survival rates were similar after TG and PG. Postoperative complication rates after PG and TG were 25.3 and 28%, respectively, (P = 0.084). Rates of reflux esophagitis and anastomotic stricture were 12 and 6.6% after PG and 2.6 and 1.3% after TG, respectively (P < 0.001 and P = 0.002). 5-year overall survival for PG and TG group was 56.7 and 46.5%, respectively (P = 0.07). Survival rates according to the tumor stage were not different between the groups. Multivariate analysis showed that type of resection was not an independent prognostic factor. CONCLUSION: Although PG for upper third GC showed good results in terms of survival, it is associated with an increased mortality rate and a higher risk of reflux esophagitis and anastomotic stricture.

Early Versus Delayed Source Control in Open Abdomen Management for Severe Intra-abdominal Infections: A Retrospective Analysis on 111 Cases.

BACKGROUND: Time to source control plays a determinant prognostic role in patients having severe intra-abdominal infections (IAIs). Open abdomen (OA) management became an effective treatment option for peritonitis. Aim of this study was to analyze the correlation between time to source control and outcome in patients presenting with abdominal sepsis and treated by OA. METHODS: We retrospectively analyzed 111 patients affected by abdominal sepsis and treated with OA from May 2007 to May 2015. Patients were classified according to time interval from first patient evaluation to source control. The end points were intra-hospital mortality and primary fascial closure rate. RESULTS: The in-hospital mortality rate was 21.6% (24/111), and the primary fascial closure rate was 90.9% (101/111). A time to source control ≥6 h resulted significantly associated with a poor prognosis and a lower fascial closure rate (mortality 27.0 vs 9.0%, p = 0.04; primary fascial closure 86 vs 100%, p = 0.02). We observed a direct increase in mortality (and a reduction in closure rate) for each 6-h delay in surgery to source control. CONCLUSION: Early source control using OA management significantly improves outcome of patients with severe IAIs. This damage control approach well fits to the treatment of time-related conditions, particularly in case of critically ill patients.

Learning curve in retroperitoneal sarcoma surgery.

INTRODUCTION: Retroperitoneal sarcoma (RPS) surgery poses unique challenges. This retrospective study aimed to analyze the learning curve (LC) in RPS surgery, assessing the relationship between surgical experience and outcomes. MATERIALS AND METHODS: Cumulative sum (CUSUM) analysis was used to analyze 62 RPS surgeries performed by a single surgeon between 2016 and 2022 at our center. RESULTS: The number of cases where the surgeon acted as first operator increased from 3 in 2016 to 13 in 2022. The surgeon operated with his mentor in 66.7 % of cases in 2016, whereas in 7.7 % of cases in 2022. LC consisted of 3 phases. Phase 1 (16 cases), with a negative slope, represented shorter operative time (OT) and fewer number of resected organs (RO). Phase 2 (30 cases) was the plateau phase. Phase 3 (16 cases), with a positive slope, indicated longer OT and more RO. Statistically significant differences were observed in terms of size (p = 0.003), presentation (p = 0.048), number of resected organs (p = 0.046), pattern of resection (p = 0.033), OT (p = 0.006), and length of stay (p = 0.026) between the three phases. CONCLUSION: This study focused on the critical role of LC in RPS surgery, emphasizing its influence on outcomes. We identified three phases, highlighting the surgeon's evolution. This offers a framework for educating sarcoma surgeons and ensuring exposure to increasing surgical complexity. In discussions on sarcoma referral centers and the correlation between case volume and outcomes, this study underlines the importance of evaluating LC to distinguish surgeons qualified to manage sarcoma cases within a referral center.

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.

Mesenchymal Tumor Management: Integrating Surgical and Non-Surgical Strategies in Different Clinical Scenarios.

Mesenchymal tumors originate from mesenchymal cells and can be either benign or malignant, such as bone, soft tissue, and visceral sarcomas. Surgery is a cornerstone treatment in the management of mesenchymal tumors, often requiring complex procedures performed in high-volume referral centers. However, the COVID-19 pandemic has highlighted this need for alternative non-surgical approaches due to limited access to surgical resources. This review explores the role of non-surgical treatments in different clinical scenarios: for improving surgical outcomes, as a bridge to surgery, as better alternatives to surgery, and for non-curative treatment when surgery is not feasible. We discuss the effectiveness of active surveillance, cryoablation, high-intensity focused ultrasound, and other ablative techniques in managing these tumors. Additionally, we examine the use of tyrosine kinase inhibitors in gastrointestinal stromal tumors and hypofractionated radiotherapy in soft tissue sarcomas. The Sarculator tool is highlighted for its role in stratifying high-risk sarcoma patients and personalizing treatment plans. While surgery remains the mainstay of treatment, integrating advanced non-surgical strategies can enhance therapeutic possibilities and patient care, especially in specific clinical settings with limitations. A multidisciplinary approach in referral centers is vital to determine the optimal treatment course for each patient.

Updates on surgical management of advanced gastric cancer: new evidence and trends. Insights from the First International Course on Upper Gastrointestinal Surgery--Varese (Italy), December 2, 2011.

Between the Ninth International Gastric Cancer Congress (IGCC) in South-Korea (Seoul, 2011) and the Tenth IGCC in Italy (Verona, 2013), the Insubria University organized the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011), with the patronage of Italian Research Group for Gastric Cancer (IRGGC) and the International Gastric Cancer Association (IGCA). The Course was intended to be a comprehensive update and review on advanced gastric cancer (GC) staging and treatment from well-known international experts. Clinical, research, and educational aspects of the surgeon's role in the era of stage-adapted therapy were discussed. As highlighted in the meeting, in this final document we summarize and thoroughly analyze (with references only for well-acquired randomized control trials) the new and old open problems in surgical management of advanced GC. Between the Ninth (Seoul, 2011) and the Tenth (Verona,2013) International Gastric Cancer Congress, the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011) was organized by the University of Insubria. This congress received the patronage of the International Gastric Cancer Association and the Italian Research Group for Gastric Cancer. The aim was to discuss open issues in surgical management of advanced gastric malignancies. We considered the opinions of several recognized experts in the field from both the Eastern and Western world, focused on definition problems and oncological and technical issues to define the current principles of advanced gastric cancer (GC) surgery.

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.

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.

Quality of life and patient satisfaction in outpatient thyroid surgery.

In the last three decades surgeons have begun to perform outpatient thyroid surgery (OTS). Important outcome measures of a day-hospital procedure are the patient's quality of life (QoL) and satisfaction, but information on these issues in the OTS setting is scanty. The aim of this pilot study was to explore how early discharge after thyroidectomy affects patients' QoL and satisfaction. Postoperative QoL and satisfaction were assessed retrospectively by giving each patient a self-report questionnaire specifically created in our center for OTS and derived from the post-discharge surgical recovery (PSR) scale to assess physical and mental well-being. Twenty-three of 24 patients (96%), 16 women and 7 men with a median age of 48 years (range 16-72), completed the questionnaire, answering 92% of the questions. QoL based on this scale gave a median score of 81.8% (range 62-98.8%). No major or minor complications occurred in the study group. Regarding QoL eight patients (35%) reported feeling "tired all the time" and six patients (26%) reported mild pain, which in two cases resolved spontaneously. Regarding patient satisfaction two-thirds of patients judged OTS positively while the remaining one-third would not recommend it. Our study showed very good uptake by patients of a new questionnaire dedicated to OTS as a possible aid in the identification of areas for improvement of OTS management. However, to be considered a safe procedure with maximum patient compliance and satisfaction, OTS was found to require considerable effort by hospital staff and patients' caregivers compared to inpatient thyroid surgery.

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.

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.