Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule.

Introduction: Regorafenib is a tyrosine kinase inhibitor (TKI) approved in metastatic gastrointestinal stromal tumor (GIST), colorectal cancer, and hepatocarcinoma. Anyway, the toxicity profile of Regorafenib standard schedule is associated with poor compliance and a high rate of discontinuation. For this reason, there is a growing need for a Regorafenib personalized schedule emerging from the scientific community. Objective: The aim of this case series was to describe the experience of our sarcoma referral center with the continuous administration of Regorafenib as an alternative regimen to treat metastatic GIST patients. Methods: We retrospectively collected clinical, pathological, and radiological data of patients with metastatic GIST treated with daily personalized Regorafenib at a single tertiary referral center from May 2021 to December 2022. Results: We identified three patients fulfilling the inclusion criteria. The average follow-up since the start of Regorafenib was 19.1 months (12-25 months). All three patients had started a standard third-line Regorafenib schedule according to guidelines. The reasons for switching to a continuous schedule were as follows: exacerbation of symptoms during week-off treatment in the first patient, a serious adverse event (AE) in the second patient, and a combination of both conditions in the third. After switching, none of the patients reported severe AEs, and they improved control of tumor-related symptoms. Two of the patients experienced disease progression after 16 months (9 months of which is continuous schedule) and 12 months (8.1 months of which is continuous schedule) of Regorafenib, respectively; the third patient is still receiving continuous Regorafenib at the time of writing, with a progression-free survival of 25 months (14 months after the modified schedule start). Conclusion: With a similar efficacy and lower toxicities, a daily, personalized Regorafenib schedule seems to be a promising alternative to the standard regimen for metastatic GIST patients, including the frail ones. Further prospective analyses are needed to confirm the safety and efficacy of such regimen.

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.

Follow-up of patients with retroperitoneal sarcoma.

Retroperitoneal sarcomas (RPS) are rare malignancies that are potentially curable by complete surgical resection. A regular surveillance program is normally commenced following surgery due to the risk of local recurrence (LR), especially in low-intermediate grade disease, and distant metastases (DM), especially in high-grade RPS. Consensus guidelines usually advocate for more frequent imaging during the first 2-3 years and less intensive imaging over a prolonged period thereafter, reflecting the incidence pattern of LR and DM. Definitive evidence for the most effective imaging schedule has never been provided, and retrospective studies have not shown an association between follow-up intensity and survival. Improvement in the prediction of recurrence patterns has been sustained by prognostic dynamic nomograms, which are now capable of forecasting disease behaviour in each patient according to specific features. Incorporation of such tools in clinical practice may help to stratify patients and tailor ongoing surveillance to the risk of recurrence. This may help to relieve patients' anxiety while awaiting results of surveillance investigations, and also reduce the economic and environmental burden of repeated imaging. A randomized controlled study (SARveillance Trial) is proposed to shed light on this controversial topic, allowing clinicians to harmonize the follow-up protocol of patients undergoing surgery for RPS.

Safe-margin surgery by plastic reconstruction in extremities or parietal trunk soft tissue sarcoma: A tertiary single centre experience.

INTRODUCTION: Tertiary centers recruit a large proportion of locally advanced or recurrent soft tissue sarcomas (STSs) that may have been preoperatively irradiated. The objective of this study was to evaluate the results of oncoplastic surgery (OPS) for patients affected by extremities or parietal trunk STS. MATERIALS AND METHODS: This retrospective study includes patients who underwent a flap reconstruction after sarcoma resection between January 2018 and December 2020 at Institut Curie. The primary endpoint was the evaluation of the impact of OPS on the quality of surgical margins. The secondary endpoint was to quantify the morbidity of OPS and identify predictive factors for wound complications. RESULTS: Of 211 patients, 89 (42.2%) had a flap reconstruction. Surgery was realized on an irradiated field in 56 (62.9%) patients. Without OPS, all patients were candidates either for amputation (n = 9,10.1%) due to vessels/nerve infiltration, or R1/R2 resection (n = 80,89.9%). Seventy-two (80.0%) pedicle flaps and 18 (20.0%) free flaps were used. No R2 resections were performed. R0 and R1 margins were achieved in 82 (92.1%) and 7 (7.9%), respectively. The median closest margin was 3 mm (IQR 1-6 mm). Among R1 patients, 5 had positive margins along a preserved critical structure, 2 patients had well-differentiated liposarcomas. The surgical morbidity rate was 33.3% (30/90 flaps). The reoperation rate was 15.7% (14/89 patients). CONCLUSIONS: In a referral sarcoma center, the collaboration between the surgical oncologist and the plastic surgery team should be considered upfront in the surgical plan, allowing the most adequate wide oncological resection with acceptable postoperative morbidity.

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.

Emergency Retroperitoneal Sarcoma Surgery for Preoperative Rupture and Hemoperitoneum: A Case Report.

Retroperitoneal sarcoma (RPS) is a rare and heterogeneous tumor. A percutaneous core needle biopsy (PCNB) is required for obtaining a histological diagnosis of the condition and for planning the therapy. Surgery is the standard of care for RPS; it is a standardized procedure, and it should be performed in a referral sarcoma center. Sarcoma surgery is rarely performed on an urgent or emergent basis. In this report, we describe a case of a retroperitoneal leiomyosarcoma that presented with spontaneous rupture and hemoperitoneum, which required surgical treatment in an urgent manner. To our knowledge, this is the first case of hemoperitoneum due to RPS rupture to be reported in the literature.

Adhesive small bowel obstruction: Single band or matted adhesions? A predictive model based on computed tomography scan.

BACKGROUND: Preoperative identification of the cause of adhesive small bowel obstruction (ASBO) is crucial for decision making. Some computed tomography (CT) findings can be indicative of single adhesive bands or matted adhesions. Our aim was to build a predictive model based on CT data to discriminate ASBO due to single adhesive band or matted adhesions. METHODS: A retrospective single center study was conducted, covering all consecutive patients with a preoperative CT scan, undergoing urgent surgery for ASBO between January 1, 2005, and December 31, 2017. Preoperative CT scans were blindly reviewed, and all the CT findings indicative of single adhesive band or matted adhesions described in literature were recorded. According to intraoperative findings, ASBOs were retrospectively classified into single band and matted ASBO. All observed CT findings were compared between the two groups. A predictive model based on logistic regression was developed, and its ability was quantified by discrimination and calibration. Internal cross-validation was conducted by bootstrap resampling. RESULTS: A total of 116 patients were analyzed (males, 53.5%; median age, 68 years; single band ASBO in 65.5% of cases). The odds of single band ASBO were increased four times in presence of complete obstruction (odds ratios, 4.19; 95% confidence interval, 1.49-12.56) and seven times in presence of fat notch sign (odds ratios, 7.37; 95% confidence interval, 1.83-40.03). The predictive model combining all CT findings had an accuracy of 86% in single band ASBO prediction. Accuracy decreased to 79% in the internal validation. Sensitivity, specificity, and positive and negative predictive values were calculated at different cut-points of the predicted risk: using a 0.70 cut-point, the specificity is 80%, the sensitivity is 68%, and the positive and negative predictive values are 87% and 57%, respectively. CONCLUSION: The proposed predictive model based on combination of specific CT findings may elucidate whether ASBO is caused by single bands or matted adhesions and, consequently, influence the clinical pathway. LEVEL OF EVIDENCE: Prognostic study, level IV.

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.

Is the outcome after hepatectomy for transitional hepatocholangiocarcinoma different from that of hepatocellular carcinoma and mass-forming cholangiocarcinoma? A case-matched analysis.

Hepatocholangiocarcinoma (HCC-CC) is a rare malignancy containing features of both hepatocellular carcinoma (HCC) and mass-forming cholangiocarcinoma (MFCCC), of which the outcome after hepatectomy remains to be clarified. The aim of this study was to analyze the characteristics and outcomes of patients with transitional HCC-CC and compare them with those of patients with HCC and MFCCC. Our prospectively maintained database was queried, and 14 transitional HCC-CC patients were identified over a total of 406 consecutive hepatic resections. A 1:1:1 match was performed with HCC and MFCCC patients operated in the same period. A total of 42 patients were matched according to tumor stage (T1-2-3, N0, M0), number of tumors, R0 resection, no 90-day mortality, and follow-up. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Disease-free survival rates at 1-, 3-, and 5-year were 71.4%, 57.1%, 35.7% for transitional HCC-CC patients; 85.7%, 40.4%, 10.1% for HCC patients; 85.1%, 34.0%, 22.7% for MFCCC patients (5-year DFS: HCC-CC vs. HCC, p = 0.575; HCC-CC vs. MFCCC, p = 0.766, respectively). Similarly, OS rates at 1-, 3-, and 5-year were 92.9%, 71.4%, 64.3% for transitional HCC-CC patients; 100%, 64.3%, 41.7% for HCC patients; 100%, 54.5%, 43.6% for MFCCC patients (5-year OS: HCC-CC vs. HCC, p = 0.891; HCC-CC vs. MFCCC, p = 0.673, respectively). When accurately matched with respect to tumor burden, transitional HCC-CC patients show similar outcomes to those of HCC and MFCCC patients. Further evaluations of differences in tumor biology are necessary to better characterize the prognosis of transitional HCC-CC patients.

Intrahepatic cholangiocellular carcinoma with radiological enhancement patterns mimicking hepatocellular carcinoma.

Non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhotic patients requires demonstration of wash-in and wash-out on contrast-enhanced imaging. Recent studies have reported misclassification of mass-forming intrahepatic cholangiocarcinoma (MFCCC) as HCC. We aimed to analyze the contrast enhancement patterns of MFCCC, focusing especially on lesions mimicking HCC. We retrospectively evaluated all consecutive patients with MFCCC who underwent surgery between 2007 and 2017. Patients with mixed HCC-MFCCC were excluded. Two expert radiologists reviewed preoperative CT and MRI. Full-nodule hyperenhancement in the arterial phase in conjunction with hypoenhancement in the portal/late phase was classified as an "HCC-like pattern". Imaging of MFCCCs with an HCC-like pattern was reviewed by an additional radiologist blinded to clinical data. Ninety-two patients were analyzed. All patients were investigated with multiphase CT and 85 with MRI. Twelve tumors (13%) showed full-nodule arterial hyperenhancement. Of these, four were hypoenhancing in the portal/late phase. Overall, 4/92 (4%) MFCCCs (4/45 in patients with cirrhosis/hepatitis, 9%) showed an HCC-like pattern accounting for misclassification as HCC on imaging review. HCC-like MFCCCs accounted for 9% of single tumors ≤ 50 mm. All HCC-like MFCCCs occurred in patients with cirrhosis or hepatitis, whereas only 47% of non-HCC-like MFCCCs did so (p = 0.053). After a median follow-up of 29 months, all patients with HCC-like MFCCCs are alive and disease free (median 64 months). In conclusion, MFCCC was misdiagnosed as typical HCC in 4% of all cases and in 9% of patients with single tumors ≤ 50 mm or with cirrhosis/hepatitis. The risk of misdiagnosis should be considered prior to treatment planning.

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.

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.