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Background: Despite the strong declining trends in incidence and mortality over the last decades, gastric cancer (GC) is still burdened with high mortality, even in high-income countries. To improve GC prognosis, several guidelines have been increasingly published with indications about the most appropriate GC management. The Italian Society of Digestive System Pathology (SIPAD) and Gastric Cancer Italian Research Group (GIRCG) designed a survey for both surgeons and patients with the purpose of evaluating the degree of application and adherence to guidelines in GC management in Italy. Materials and Methods: Between January and May 2022, a questionnaire has been administered to a sample of Italian surgeons and, in a simplified version, to members of the Patient Association “Vivere Senza Stomaco” (patients surgically treated for GC between 2008 and 2021) to investigate the diagnosis, staging, and treatment issues. Results: The survey has been completed by 125 surgeons and 125 patients. Abdominal CT with gastric hydro-distension before treatment was not widespread in both groups (47% and 42%, respectively). The rate of surgeons stating that they do not usually perform minimally invasive gastrectomy was 15%, but the rate of patients who underwent a minimally invasive approach was 22% (between 2011 and 2022). The percentage of surgeons declaring to perform extended lymphadenectomy (>D2) was 97%, although a limited lymph node dissection rate was observed in about 35% of patients. Conclusions: This survey shows several important discrepancies from surgical attitudes declared by surgeons and real data derived from the reports available to the patients, suggesting heterogeneous management in clinical practice and, thus, a not rigorous adherence to the guidelines.

Approximately 10–12% of patients with oesophageal or gastric cancer (OGC) present with oligometastatic disease at diagnosis. It remains unclear if there is a role for radical surgery in these patients. We aimed to assess the outcomes of OGC patients who underwent simultaneous treatment for the primary tumour and synchronous liver metastases. Patients with OGC who underwent surgical treatment between 2008 and 2020 for the primary tumour and up to five synchronous liver metastases aiming for complete tumour removal or ablation (i.e., no residual tumour) were identified from four institutional databases. The primary outcome was overall survival (OS), calculated with the Kaplan–Meier method. Secondary outcomes were disease-free survival and postoperative outcomes. Thirty-one patients were included, with complete follow-up data for 30 patients. Twenty-six patients (84%) received neoadjuvant therapy followed by response evaluation. Median OS was 21 months [IQR 9–36] with 2- and 5-year survival rates of 43% and 30%, respectively. While disease recurred in 80% of patients (20 of 25 patients) after radical resection, patients with a solitary liver metastasis had a median OS of 34 months. The number of liver metastases was a prognostic factor for OS (solitary metastasis aHR 0.330; p-value = 0.025). Thirty-day mortality was zero and complications occurred in 55% of patients. Long-term survival can be achieved in well-selected patients who undergo surgical resection of the primary tumour and local treatment of synchronous liver metastases. In particular, patients with a solitary liver metastasis seem to have a favourable prognosis.

Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a mechanism potentially involved in trastuzumab-acquired resistance. FGFR inhibition could be a potential mechanism as a second-line treatment. In this Simon’s two-stage phase 2, single arm study, patients with advanced EG cancer refractory to trastuzumab-containing therapies received pemigatinib, an inhibitor of FGFR. The primary end point was the 12-week progression-free survival rate. Translational analyses were performed on tissue and plasma samples. Eight patients were enrolled in the first stage. Although the 6-week disease control rate was 25%, only one patient achieved a stable disease after 12 weeks of treatment. The trial was discontinued before the second stage. Two out of six evaluable tumor samples expressed FGFR3. No FGFRs amplification was detected. HER2 amplification was lost in three out of eight patients. Three patients had an high Tumor Mutational Burden, and two of them are significantly long-term survivors. These results do not support the therapeutic efficacy of targeting FGFR in unselected patients with advanced EG cancer, who are refractory to trastuzumab-containing therapies.

BackgroundThe near-infrared/indocyanine green imaging fluorescence (NIR/ICG) technology is showing promising results in several fields of surgical oncology. The clinical value of NIR/ICG technology in the surgical treatment of advanced gastric cancer (AGC) is not clearly established.MethodsThis is the protocol of the “iGreenGO” (indocyanine Green Gastric Observation) Study, a national prospective multicenter study. Western patients who undergo curative-intent gastrectomy with D2 lymphadenectomy for AGC constitute the study cohort. All the patients undergo preoperative upper gastrointestinal endoscopy for submucosal peritumoral ICG injection at the most 20 h before surgery. Intraoperative endoscopic injection before starting surgical dissection is also allowed. The primary endpoint is the “change in the surgical conduct” (CSC), i.e., the need to perform further dissection after intraoperative NIR/ICG technology activation at the end of D2 lymphadenectomy. Secondary endpoints include the pattern of abdominal fluorescence distribution according to tumor and patient characteristics, the preoperative clinical variables potentially associated with CSC, and the incidence of stage migration due to NIR/ICG application.DiscussionThe iGreenGO Study is the first study to investigate the clinical role of NIR/ICG technology for the surgical treatment of AGC in a large cohort of Western patients. Results from the present study can further clarify the role of NIR/ICG technology in surgical lymphadenectomy for AGC.

Abstract Background To review the available clinical data about the value of Indocyanine Green (ICG) fluorescence imaging for intraoperative detection of peritoneal carcinomatosis. Methods We conducted a systematic review, according to the PRISMA guidelines, for clinical series investigating the possible role of ICG fluorescence imaging in detecting peritoneal carcinomatosis during surgical treatment of abdominal malignancies. With the aim to analyze actual application in the daily clinical practice, papers including trials with fluorophores other than ICG, in vitro and animals series were excluded. Data on patients and cancer features, timing, dose and modality of ICG administration, sensitivity, specificity and accuracy of fluorescence diagnosis of peritoneal nodules were extracted and analyzed. Results Out of 192 screened papers, we finally retrieved 7 series reporting ICG-guided detection of peritoneal carcinomatosis. Two papers reported the same cases, thus only 6 series were analyzed, for a total of 71 patients and 353 peritoneal nodules. The investigated tumors were colorectal carcinomas in 28 cases, hepatocellular carcinoma in 16 cases, ovarian cancer in 26 cases and endometrial cancer in 1 case. In all but 4 cases, the clinical setting was an elective intervention in patients known as having peritoneal carcinomatosis. No series reported a laparoscopic procedure. Technical data of ICG management were consistent across the studies. Overall, 353 lesions were harvested and singularly evaluated. Sensitivity varied from 72.4 to 100%, specificity from 54.2 to 100%. Two series reported that planned intervention changed in 25 and 29% of patients, respectively. Conclusion Indocyanine Green based fluorescence of peritoneal carcinomatosis is a promising intraoperative tool for detection and characterization of peritoneal nodules in patients with colorectal, hepatocellular, ovarian carcinomas. Further prospective studies are needed to fix its actual diagnostic value on these and other abdominal malignancies with frequent spread to peritoneum.

Background and ObjectiveThe aim of this study was to assess the ability of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) to provide functional information useful in predicting pathological response to an intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for both esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) patients.Material and MethodsEsophageal carcinoma (EC) patients, treated in our Center between 2014 and 2018, were retrospectively reviewed. The nCRT protocol schedule consisted of an induction phase of weekly administered docetaxel, cisplatin, and 5-fluorouracil (TCF) for 3 weeks, followed by a concomitant phase of weekly TCF for 5 weeks with concurrent radiotherapy (50–50.4 Gy in 25–28 fractions). Three 18F-FDG PET/CT scans were performed: before (PET1) and after (PET2) induction chemotherapy (IC), and prior to surgery (PET3). Correlation between PET parameters [maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)], radiomic features and tumor regression grade (TGR) was investigated.ResultsFifty-four patients (35 ADC, 19 SCC; 48 cT3/4; 52 cN+) were eligible for the analysis. Pathological response to nCRT was classified as major (TRG1-2, 41/54, 75.9%) or non-response (TRG3-4, 13/54, 24.1%). A major response was statistically correlated with SCC subtype (p = 0.02) and smaller tumor length (p = 0.03). MTV and TLG measured prior to IC (PET1) were correlated to TRG1-2 response (p = 0.02 and p = 0.02, respectively). After IC (PET2), SUVmean and TLG correlated with major response (p = 0.03 and p = 0.04, respectively). No significance was detected when relative changes of metabolic parameters between PET1 and PET2 were evaluated. At textural quantitative analysis, three independent radiomic features extracted from PET1 images ([JointEnergy and InverseDifferenceNormalized of GLCM and LowGrayLevelZoneEmphasis of GLSZM) were statistically correlated with major response (p < 0.0002).Conclusions18F-FDG PET/CT traditional metrics and textural features seem to predict pathologic response (TRG) in EC patients treated with induction chemotherapy followed by neoadjuvant chemo-radiotherapy. Further investigations are necessary in order to obtain a reliable predictive model to be used in the clinical practice.

Background: Prognosis of patients affected by metastatic esophageal–gastric junction (EGJ) or gastric cancer (GC) remains dismal. Trastuzumab, an anti-HER2 monoclonal antibody, is the only targeted agent approved for the first-line treatment of patients with HER2-overexpressing advanced EGJ or GC in combination with chemotherapy. However, patients invariably become resistant during this treatment. We recently identified the overexpression of fibroblast growth factor (FGF) receptor 3 (FGFR3) as a molecular mechanism responsible for trastuzumab resistance in GC models, providing the rationale for the inhibition of this receptor as a potential second-line strategy in this disease. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. Methods: The FiGhTeR trial is a phase II, single-arm, open-label study to assess safety and activity of the FGFR inhibitor pemigatinib as second-line treatment strategy in metastatic EGJ/GC patients progressing under trastuzumab-containing therapies. The primary endpoint is the 12-week progression-free survival rate. Plasma and tumor tissue samples will be collected for translational research analyses at baseline, during treatment, and at progression on pemigatinib. Discussion: Co-alterations in genes coding for different tyrosine-kinase receptors are emerging as relevant mechanisms of acquired resistance to anti-HER2 therapeutic strategies in GC. In particular, our group has recently identified that in GC models the overexpression of FGFR3 sustains the acquired resistance to trastuzumab. This trial aims to assess the safety, tolerability and activity of the FGFR inhibitor pemigatinib as a second-line treatment in metastatic EGJ/GC patients refractory to first-line trastuzumab-containing therapies. Furthermore, this study offers the opportunity to prospectively study mechanisms and pathways involved in trastuzumab resistance. Protocol number: CRC2017_02 EudraCT Number: 2017-004522-14

Background:After the results reported by the “Chemoradiotherapy for esophageal Cancer Followed by Surgery Study” (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Methods: Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. Results: The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively (p ≦ 0.001). Conclusions: Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences.

Background: A phase II intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for esophageal cancer (EC) was previously tested at our Center with promising results. We here present an observational study to evaluate the efficacy of the protocol also in “real life” patients. Methods: We retrospectively reviewed 122 ECs (45.1% squamous cell (SCC) and 54.9% adenocarcinoma (ADC)) treated with induction docetaxel, cisplatin, and 5-fluorouracil (TCF), followed by concomitant TCF and radiotherapy (50–50.4 Gy/25–28 fractions), between 2008 and 2017. Primary endpoints were overall survival (OS), event-free survival (EFS) and pathological complete response (pCR). Results: With a median follow-up of 62.1 months (95% CI 50–67.6 months), 5-year OS and EFS rates were 54.8% (95% CI 44.7–63.9) and 42.7% (95% CI 33.1–51.9), respectively. A pCR was observed in 71.1% of SCC and 37.1% of ADC patients (p = 0.001). At multivariate analysis, ypN+ was a significant prognostic factor for OS (Hazard Ratios (HR) 4.39 [95% CI 2.36–8.18]; p < 0.0001), while pCR was a strong predictor of EFS (HR 0.38 [95% CI 0.22–0.67]; p < 0.0001). Conclusions: The nCRT protocol achieved considerable long-term survival and pCR rates also in “real life” patients. Further research is necessary to evaluate this protocol in a watch-and-wait approach.

Aim. To investigate the role of maximum tumour diameter (D-max) reduction rate at CT examination in predicting histopathological tumour regression grade (TRG according to the Becker grade), after neoadjuvant chemotherapy (NAC), in patients with resectable advanced gastric cancer (AGC). Materials and Methods. Eighty-six patients (53 M, mean age 62.1 years) with resectable AGC (≥T3 or N+), treated with NAC and radical surgery, were enrolled from 5 centres of the Italian Research Group for Gastric Cancer (GIRCG). Staging and restaging CT and histological results were retrospectively reviewed. CT examinations were contrast enhanced, and the stomach was previously distended. The D-max was measured using 2D software and compared with Becker TRG. Statistical data were obtained using “R” software. Results. The interobserver agreement was good/very good. Becker TRG was predicted by CT with a sensitivity and specificity, respectively, of 97.3% and 90.9% for Becker 1 (D-max reduction rate > 65.1%), 76.4% and 80% for Becker 3 (D-max reduction rate

Background: Although the Japan Clinical Oncology Group (JCOG) 9501 trial did not find that prophylactic D3 lymphadenectomy led to any survival advantage over D2 lymphadenectomy, it did find that the prognosis of subserosal and N0 gastric cancer patients improved. The aim of this retrospective observational study was to compare survival after D2 or D3 lymphadenectomy in different patient subgroups. Methods: The study considered all of the patients who underwent D2 or D3 lymphadenectomy at a high-volume center in Verona (Italy) between 1992 and 2011. After excluding patients with Bormann IV or neuroendocrine tumors, early gastric cancers, or non-curative resections, the analysis involved 301 R0 patients: 100 who underwent D2, and 201 who underwent D3 lymphadenectomy. Post-operative deaths and deaths due to recurrences were considered as terminal events in the survival analysis. Results: The D2 patients were significantly older than the D3 patients at baseline (69.8 ± 2.3 vs. 62.2 ± 10.7 years). The median number of retrieved nodes was 29 (interquartile range: 24.5−39) after D2, and 43 (34−52) after D3. The five-year disease-related survival rate was similar after D2 (44%, 95% confidence interval (CI) 34−54%) and D3 (41%, 34−48%) (p = 0.766). A Cox model controlling for sex, age, tumor site, Laurén histology, and T and N stages showed that the risk of cancer-related death after D3 was similar to that recorded after D2 (hazard ratio 0.97, 95% CI 0.67−1.42). There was a significant interaction between the T status and the extension of the lymphadenectomy (p = 0.012), with the prognosis being better after D2 in T2 and T4b patients, and after D3 in T3 patients. Conclusions: The findings of this study suggest that D3 lymphadenectomy is not routinely indicated for patients with advanced gastric cancer, although differences in survival after D3 across T tiers deserve further consideration.

The application of enhanced recovery after surgery guidelines for esophageal surgery in different units remains unclear. This survey intended to investigate how such protocol is applied among Italian esophageal surgery units. A survey with 40 questions was mailed to Italian centers that performed at least 10 esophagectomies per year. It included questions about the type of hospital and unit and pre-, intra- and post-operative items. Difficulties encountered were investigated. Thirteen (65%) centers answered the survey, and all met the minimal safety requirements, e.g., the presence of intensive care units and 24-h on-call operative endoscopy and radiology facilities. Fifty percent of esophagectomies with a minimally invasive approach were performed in 84.6% of the centers. Regarding pre-operative items, the highest scores were for the application of nutritional support, dysphagia palliation and presence of a multidisciplinary tumor board, whereas the lowest score was for the use of immunonutrition. Regarding intra-operative items, hypothermia prevention and the use of goal-directed fluid therapy and volatile anesthesia were diffusely adopted, whereas the rate of using abdominal drains was high. Regarding post-operative items, nausea prevention, multimodal analgesia and early mobilization were applied frequently, whereas the use of nasogastric tubes and regular transfer to intensive care units was diffused. The primary barriers in enhanced recovery after surgery protocol application were resistance and a lack of paramedic personnel. This survey's results highlight the efforts undertaken by several centers to apply enhanced recovery after surgery philosophy and in this regard, demonstrate a good standing in Italy. [ABSTRACT FROM AUTHOR]