Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer.

BACKGROUND: A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). METHODS: Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). RESULTS: The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . CONCLUSIONS: We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.

A detailed analysis of the recurrence timing and pattern after curative surgery in patients undergoing neoadjuvant therapy or upfront surgery for gastric cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether the administration of neoadjuvant therapy (NAD) affects the incidence, timing, and pattern of recurrence in patients treated by curative gastrectomy. METHODS: Sixty-nine patients undergoing NAD and R0 gastrectomy were compared with 198 patients undergoing upfront surgery using the propensity score matching (PSM) method. Disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) analyses were conducted with a log-rank test and Cox regression. Risk factors for recurrence were assessed by logistic regression. RESULTS: Among 69 patients with NAD, 28 (40.6%) experienced recurrence, and signet-ring cell (SRC) carcinoma was the only factor independently associated with recurrence. In the whole sample, NAD did not influence DFS, DSS, rate of recurrence, or PFS. After PSM, the variables associated with DFS were cN1, type of gastrectomy, the presence of SRCs, and the presence of lymphovascular invasion. Variables independently associated with recurrence were cN1, type of gastrectomy, and the presence of SRCs. CONCLUSIONS: NAD had no impact on DFS, DSS, or the pattern of recurrence in any patients with gastric cancer. To define a better treatment strategy, future studies should focus on subtypes that do not respond to the current neoadjuvant regimens.

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.

Profiling complete regression after pre-operative therapy in gastric cancer patients using clinical and pathological data.

INTRODUCTION: The consistent use of pre-operative treatment before surgery for gastric cancer (GC) has resulted in increased rates of complete response. However, factors associated with response have been scantly investigated. METHODS: Patients with GCs treated between 2017 and 2022 undergoing pre-operative treatment followed by resection were included. Clinicopathological data were analyzed for the association with tumor regression grades (TRG); secondary outcomes included the short-term overall (OS), disease-free (DFS) and disease specific survival (DSS). RESULTS: Among 108 patients, 35.1% had an intestinal histotype GC, and 70.4% were treated with FLOT. Complete tumor regression (TRG1) was documented in 6.5% of patients. Univariable analyses documented that a higher pre-operative albumin (p = 0.04) and the expression of HER2 (p = 0.01) were associated to TRG1. In the multinominal regression model, the log-odds of being classified as TRG1 increased with the expression of HER2 by 170.247 times and with higher pre-operative albumin by 34.525 times, while with a higher Charlson Index and a diffuse hystotipe reduced it by 25.467 times and 3759.126 times, respectively. Among 49 patients (mean follow-up: 17.1 months), TRG1-2 was associated to better OS, DFS and DSS curves compared to TRG 3-5 (respectively p < 0.01, p 0.007 and p < 0.01), altogether with the reported negative impact of comorbidities in OS and DSS multivariable analyses (respectively p 0.04 and p 0.006). The random survival forest further confirmed the impact of HER2 and comorbidity on DSS. CONCLUSION: A better clinical profile, HER2 expression and intestinal histotype significantly correlated with GC regression. A complete-major response was an independent factor for survival.

The definition of "R1" lymph node dissection status in patients undergoing curative-aim gastrectomy for gastric carcinoma: A proof of concept study.

INTRODUCTION: The aim of this study was to define and investigate the prognostic impact of "R1-Lymph-node dissection" during gastrectomy. METHODS: This was a retrospective study conducted with 499 patients undergoing curative-aim gastrectomy. We defined R1-Lymph dissection as an involvement of lymph node stations anatomically connected with lymph node stations outside the declared level of dissection (D1 to D2+). The primary outcomes were disease-free and disease-specific survival (DFS and DSS). RESULTS: At multivariable analysis, the type of gastrectomy, pT and pN were associated with DFS, and the type of gastrectomy, R1-Margin status, R1-Lymph status, pT, pN and adjuvant therapy were associated with DSS. Moreover, pT and R1-Lymph status were the only factors associated with overall loco-regional recurrence. CONCLUSIONS: In this study, we introduced the concept of R1-Lymph-node dissection, which was significantly associated with DSS and appeared to be a stronger prognostic factor for loco-regional recurrence than the R1 status on the resection margin.

The Use of Indocyanine Green (ICG) and Near-Infrared (NIR) Fluorescence-Guided Imaging in Gastric Cancer Surgery: A Narrative Review.

Near-infrared fluorescence imaging with indocyanine green is an emerging technology gaining clinical relevance in the field of oncosurgery. In recent decades, it has also been applied in gastric cancer surgery, spreading among surgeons thanks to the diffusion of minimally invasive approaches and the related development of new optic tools. Its most relevant uses in gastric cancer surgery are sentinel node navigation surgery, lymph node mapping during lymphadenectomy, assessment of vascular anatomy, and assessment of anastomotic perfusion. There is still debate regarding the most effective application, but with relatively no collateral effects and without compromising the operative time, indocyanine green fluorescence imaging carved out a role for itself in gastric resections. This review aims to summarize the current indications and evidence for the use of this tool, including the relevant practical details such as dosages and times of administration.

Global updates in the treatment of gastric cancer: a systematic review. Part 1: staging, classification and surgical treatment.

Gastric cancer (GC) is the fifth malignancy and the third cause of cancer death worldwide, according to the global cancer statistics presented in 2018. Its definition and staging have been revised in the eight edition of the AJCC/TNM classification, which took effect in 2018. Novel molecular classifications for GC have been recently established and the process of translating these classifications into clinical practice is ongoing. The cornerstone of GC treatment is surgical, in a context of multimodal therapy. Surgical treatment is being standardized, and is evolving according to new anatomical concepts and to the recent technological developments. This is leading to a massive improvement in the use of mini-invasive techniques. Mini-invasive techniques aim to be equivalent to open surgery from an oncologic point of view, with better short-term outcomes. The persecution of better short-term outcomes also includes the optimization of the perioperative management, which is being implemented on large scale according to the enhanced recovery after surgery principles. In the era of precision medicine, multimodal treatment is also evolving. The long-time-awaited results of many trials investigating the role for preoperative and postoperative management have been published, changing the clinical practice. Novel investigations focused both on traditional chemotherapeutic regimens and targeted therapies are currently ongoing. Modern platforms increase the possibility for further standardization of the different treatments, promote the use of big data, and open new possibilities for surgical learning. This systematic review in two parts assesses all the current updates in GC treatment.