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Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13-106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13-18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival.

Aim: To investigate the impact of natremia in metastatic colorectal cancer (mCRC) patients treated with aflibercept plus folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRI). Patients & methods: A total of 84 mCRC patients receiving aflibercept plus FOLFIRI as second-line treatment were enrolled and divided into two groups based on their median sodium value. Progression-free survival and overall survival were analyzed. Results: Patients with sodium levels ≥140 mEq/l had significantly longer median progression-free survival (4.1 vs 2 months; p < 0.01) and median overall survival (12 vs 7.3 months; p < 0.01) compared with those with lower levels. Conclusion: This study suggests that higher pretreatment serum sodium levels are associated with improved outcomes in mCRC patients receiving aflibercept and FOLFIRI, potentially serving as a prognostic marker to aid treatment management.

The phase III MPACT trial demonstrated the superiority of gemcitabine plus nab-paclitaxel (NABGEM) versus gemcitabine alone in previously untreated patients with metastatic pancreatic cancer (mPC). The aim of this study was to evaluate the responses in terms of efficacy and safety in patients treated with more than 6 cycles of chemotherapy. From January 2015 to December 2018, patients with mPC receiving first-line treatment with NABGEM were included in a multicentre retrospective observational study. Exploratory analyses of efficacy and safety were performed. The cohort included 153 patients with performance status of 1. The median overall survival and progression-free survival were 20 months (hazard ratio [HR] 0.28, 95% confidence interval [CI]: 0.17-0.44) and 10 months (HR 0.24 95% CI: 0.16-0.38) respectively, in patients who received >6 cycles compared to 9 and 5 months in those treated with ≤6 cycles ( p  < 0.001). The disease control rate was 100% versus 56% in patients receiving >6 and ≤6 cycles, respectively. No progression of disease was recorded in patients who received >6 cycles. Grade 1 neuropathy and grade 3 neutropenia were more frequent in patients treated with >6 cycles compared to patients receiving ≤6 cycles ( p  = 0.01; p  = 0.03, respectively). Dose reduction was necessary for 70.1% and 53.4% of patients treated with >6 or ≤6 cycles, whereas treatment interruption occurred in 37.1% and 21.6%, respectively. Our results confirmed the efficacy and safety of NABGEM in untreated mPC. In particular, we highlighted significant clinical efficacy in patients who received >6 cycles of chemotherapy compared to those who received ≤6 cycles, with manageable toxicity profile.

Background: With the availability of multiple treatment options for metastatic castration-resistant prostate cancer (mCRPC), new real-world data on disease management and drugs' performance are needed., Methods: We described characteristics, management and clinical outcomes of patients receiving first-line mCRPC treatment within the Italian cohort of the real-world, prospective, international Prostate Cancer Registry. Patients were enrolled consecutively (2013-2016) in 32 Italian sites and followed for 3 years., Results: 238 patients were included: 157 received first-line abiraterone acetate plus prednisone ("abiraterone" thereafter) and 70 first-line docetaxel; 11 patients receiving other treatments were not considered. Compared with docetaxel-treated patients, those receiving abiraterone were significantly older (age ⩾75: 63.7% vs 38.6%), less frequently had a Gleason score >8 (48.2% vs 67.6%, p<0.005) at initial diagnosis, and more frequently an ECOG score ⩾1 (52.7% vs 36.2%, p<0.05) and comorbidities (76.4% vs 57.1%, p<0.05) at baseline; they reported a lower analgesic use (15.3% vs 30%, p<0.005). In the abiraterone group (median follow-up 22.1 months), median time to progression (TTP) and progression-free survival (PFS) were, respectively, 14.4 months (95% confidence interval, CI, 10.6-18.0) and 13.0 months (95% CI, 9.1-16.8); median overall survival (OS) was not reached, and 3-year OS was 59.1%. In the docetaxel treatment group (median follow-up 25.3 months), median TTP, PFS and OS were, respectively, 8.2 months (95% CI, 6.1-10.3), 8.2 months (95% CI, 5.8-10.3) and 33.2 months (95% CI, 19.2-not estimable)., Conclusion: This investigation provided valuable information on the overall mCRPC treatment pattern and the effectiveness of first-line abiraterone and docetaxel in a population representative of everyday practice.

Background: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. This study evaluated the prognostic role of serum alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT) in metastatic PC patients. Materials & methods: 153 patients with metastatic PC receiving first-line treatment with nab-paclitaxel/gemcitabine were retrospectively enrolled in a multicenter study and stratified according to ALP (≤ or >260 U/l) and GGT (≤ or >45.5 U/l) levels. Results: Improved overall survival was recorded in patients with GGT levels ≤45.5 U/l (p < 0.05). In patients with liver metastasis, overall survival was significantly lower in patients with high ALP (p = 0.01) and GGT (p = 0.02). Conclusion: High levels of ALP and GGT were related to a poor prognosis in PC patients with liver metastasis receiving nab-paclitaxel/gemcitabine.

Background: Gastro-entero-pancreatic neuroendocrine tumors are gradually seeing their incidence increase, probably due to their low-rate mortality. Surgery and subsequent medical therapy through octeotride and somatostatin analogues is the recommended approach for hypersecretive hormonal forms, showing an effective control of symptoms and improved survival outcomes., Aim: The present study aims to evaluate the occurrence of gallbladder lithiasis, and its complications, in patients underwent upfront surgery for neuroendocrine tumors and subsequent long-term administration of somatostatin analogues., Material of Study: We included four adults affected by neuroendocrine (gastric, appendiceal and ileal) tumors and without previous evidence of gallbladder stones, who needed an emergency cholecystectomy after long-term somatostatin treatment., Results: The patients showed complicated conditions sustained by cholelithiasis, such as acute cholecystitis, gangrenous cholecystitis, or intestinal occlusion, which required emergency surgery., Discussions: Somatostatin analogues may influence the cascade of enzymes that guarantee the gallbladder motility, and consequently cause the precipitation of cholesterol and calcium bilirubinate crystals. Therefore, higher and sustained levels of somatostatin may result in higher rates of gallstone development., Conclusions: The prophylactic cholecystectomy, during upfront surgery for neuroendocrine tumors, might prevent an emergency cholecystectomy for gallstones complications., Key Words: Gallbladder stones, Neuroendocrine tumors, Somatostatine analogues.

Background: Although the prognostic value of the epithelial-to-mesenchymal transition (EMT) in gastric cancer has been reported in several studies, the strong association with the diffuse type may represent a confounding factor. Our aim is to investigate potential correlations among EMT status, tumor advancement, and prognosis in diffuse gastric cancer. Methods: Between 1997 and 2012, 84 patients with microsatellite-stable (MSS) diffuse-type tumors underwent surgery. The EMT phenotype was assessed with the E-cadherin, CD44, and zinc finger E-box binding homeobox 1 (ZEB-1) immunohistochemical markers. Results: Forty-five out of 84 cases (54%) were EMT-positive; more advanced nodal status (p = 0.010), pTNM stage (p = 0.032), and vascular invasion (p = 0.037) were observed in this group. The median numbers of positive nodes (13 vs. 5) and involved nodal stations (4 vs. 2) were higher in the EMT-positive group. The cancer-related survival time was 26 months in EMT-positive cases vs. 51 in negative cases, with five-year survival rates of 17% vs. 51%, respectively (p = 0.001). The EMT status had an impact on the prognosis of patients with <70 years, R0 resections, or treatment with adjuvant chemotherapy. Tumor relapses after surgery and peritoneal spread were significantly higher in the EMT-positive tumors. Conclusions: EMT status, when assessed through immunohistochemistry, identified an aggressive phenotype of MSS diffuse-type tumors with extensive lymph nodal spread, peritoneal dissemination, and worse long-term outcomes.

Background and Objectives: Only recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC., Methods: A retrospective analysis was performed through a prospectively maintained database of patients with diagnosed "mixed-type" gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: "Group 1" (displaying ≤10% of SRCs), "Group 2" (displaying <90% but >10% of SRCs), and "Group 3" (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups., Results: Among 164 enrolled patients, 68.9% were male and 31.1% were female ( p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as "Group 1", 66 (40.3%) as "Group 2", and none as "Group 3". Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72-4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival., Conclusions: The proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marano, Ambrosio, Resca, Carbone, Carpineto Samorani, Petrioli, Savelli, Costantini, Malaspina, Polom, Biviano, Marrelli and Roviello.)

Few studies have evaluated the impact of risk factors such as performance status (PS) and comorbidities on overall survival (OS) in patients with metastatic pancreatic cancer (mPC). We investigated the influence of comorbidity, PS and age on nab-paclitaxel and gemcitabine (NabGem) effectiveness profile in naive patients with mPC. 153 patients with mPC treated with NabGem upfront was divided in three groups (score 0 to 3) based on the absence or the presence of one or more risk factors among: age ≥ 70 years, PS 1 and comorbidities and the clinical outcomes was compared. Fifty-five patients were elderly (≥ 70 years), 80 patients have PS 1, whereas the other have PS 0. Patients with no risk factors (score 0) had an overall survival higher (20 months) than patients with one or two risk factors (score 1-2) (OS 11 months) and with three risk factors (score 3) (OS 8 months) (p < 0.01). The difference in OS was also statistically significant in patients without comorbidities (OS 15 months) compared to those with ≥ 1 comorbidity (OS 10 months) (p < 0.001). NabGem chemotherapy represent an effective treatment in naive patients. Age, PS, and comorbidities were prognostic factors in patients with metastatic pancreatic cancer., (© 2022. The Author(s).)

Background and Objectives: Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA., Methods: We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: "pure" SRC (containing ≥90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC-NOS) (containing ≤10% of SRCs), and PC-NOS/SRC (containing <90% but >10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared., Results: Among 143 enrolled patients, 51% were male and 49% were female. The mean (±SD) age at diagnosis was 61 ± 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as "pure" SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than four-fold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5-7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival., Conclusions: The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients., Methods: Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up)., Results: In the final round, 23 out of 24 items obtained agreement ( ≥ 8) and consensus ( ≤ 2) and 19 out 24 items obtained a good stability (p > 0.05)., Conclusions: The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making., Key Points: • Imaging represents the cornerstone for tailored treatment in GC patients. • CT-structured radiology report in GC patients is useful for multidisciplinary decision making., (© 2021. European Society of Radiology.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent adverse events observed with taxane use, whose disability often required modification or treatment discontinuation. The aim of this study was to assess the value of several variables as risk factors for CIPN development., Material and Methods: Eligible patients with metastatic pancreatic cancer receiving chemotherapy with nab-paclitaxel and gemcitabine were assessed in a multicenter study. Peripheral neuropathy was categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02, and a physical/neurological examination. Univariate and multivariate regression analyses were used to identify blood-based and clinical factors associated with CIPN., Results: Data were available from 153 patients from five Italian centers. Key risk factors of CIPN in univariate regression models included age, number of chemotherapy cycles, statin assumption, and concomitant comorbidities. However, in the multivariate analysis, only for age (OR 1.0, p < 0.01, 95% CI: 1.01-1.11) and the number of cycles (OR 1.22, p < 0.01, 95% CI: 1.09-1.36), the correlation with CIPN development has been confirmed., Conclusion: Our study confirms age and the number of chemotherapy cycles as CIPN risk factors. The identification and validation of different risk factors could be advantageous to prevent or optimize management of CIPN which outstandingly affect the patient's quality of life., (© 2022 S. Karger AG, Basel.)