The Learning Curve for Robotic Lateral Pelvic Lymph Node Dissection for Rectal Cancer: A View from the West.

BACKGROUND: Lateral pelvic lymph-node dissection is performed for selected patients with rectal cancer with persistent lateral nodal disease after neoadjuvant therapy. This technique has been slow to be adopted in the West due to concerns regarding technical difficulty. This is the first report on the learning curve for lateral pelvic lymph node dissection in the US or Europe. OBJECTIVE: The aim of this study was to analyze the learning curve associated with robotic lateral pelvic lymph node dissection. DESIGN: Retrospective observational cohort. SETTING: Tertiary academic cancer center. PATIENTS: Consecutive patients from 2012 to 2021. INTERVENTION: All patients underwent robotic lateral pelvic lymph node dissection. MAIN OUTCOME MEASURES: The primary endpoints were the learning curves for maximum number of nodes retrieved and urinary retention which was evaluated with simple cumulative-sum and two-sided Bernoulli cumulative-sum charts. RESULTS: Fifty-four procedures were included. A single-surgeon (n = 35) and an institutional learning curve are presented in the analysis. In the single-surgeon learning curve, a turning point marking the end of a learning phase was detected at the 12th procedure for the number of retrieved nodes and at the 20th for urinary retention. In the institutional learning curve analysis, two turning points were identified at the 13th and 26th procedures indicating progressive improvements for the number of retrieved nodes and at the 27th for urinary retention. No sustained alarm signals were detected at any time point. LIMITATIONS: The retrospective nature, small sample size and the referral center nature of the reporting institution that may limit generalizability. CONCLUSIONS: In a setting of institutional experience with robotic colorectal surgery including beyond TME resections, the learning curve for robotic lateral pelvic lymph node dissection is acceptably short. Our results demonstrate feasibility of acquisition of this technique in a controlled setting, with sufficient case volume and proctoring can optimize the learning curve. See Video Abstract.

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: The aim of this study was to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values, and compare these models' accuracy to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative day 1 to 3 were collected. Models of complications and readmission risk were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult colorectal cancer patients. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative major complication, readmission and anastomotic leak using the area under the receiver-operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak (p = 0.036) and readmission using postoperative day 1-2 values (p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as soon as postoperative day 2. See Video Abstract.

Clostridium difficile infection after stoma reversal surgery: a systematic review and meta-analysis of the literature.

BACKGROUND: Clostridium difficile infection (CDI) has been described in the early post-operative phase after stoma reversal. This systematic review aimed to describe the incidence of CDI after stoma reversal and to identify pre-operative variables correlated with an increased risk of infection. METHODS: A systematic review of the literature was conducted according to the PRISMA guidelines in March 2024. Manuscripts were included if reported at least one patient with CDI-associated diarrhoea following stoma reversal (colostomy/ileostomy). The primary outcome of interest was the incidence of CDI; the secondary outcome was the comparison of clinical variables (age, sex, time to stoma reversal, neo-adjuvant and adjuvant therapies after index colorectal procedure) in CDI-positive versus CDI-negative patients. A meta-analysis was performed when at least three studies reported on those variables. RESULTS: Out of 43 eligible manuscripts, 1 randomized controlled trial and 10 retrospective studies were selected, including 17,857 patients (2.1% CDI). Overall, the mean age was 64.3 ± 11.6 years in the CDI group and 61.5 ± 12.6 years in the CDI-negative group (p = 0.51), with no significant difference in sex (p = 0.34). Univariable analyses documented that the mean time to stoma reversal was 53.9 ± 19.1 weeks in CDI patients and 39.8 ± 15.0 weeks in CDI-negative patients (p = 0.40) and a correlation between neo-adjuvant and adjuvant treatments with CDI (p < 0.001). A meta-analysis was performed for time to stoma reversal, age, sex, and neo-adjuvant therapies disclosing no significant differences for CDI (stoma delay, MD 11.59; 95%CI  24.32-1.13; age, MD 0.97; 95%CI 2.08-4.03; sex, OR1.11; 95%CI 0.88-1.41; neo-adjuvant, OR0.81; 95%CI 0.49-1.35). Meta-analysis including patients who underwent adjuvant therapy evidenced a higher risk of CDI (OR 2.88; 95%CI 1.01-8.17, p = 0.11). CONCLUSION: CDI occurs in approximately 2.1% of patients after stoma reversal. Although a trend of increased delay in stoma reversal and a correlation with chemotherapy were documented in CDI patients, the use of adjuvant therapy was the only possible risk factor documented on meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42023484704.

Clinical Impact of Positive Surgical Margins in Gastric Adenocarcinoma in the Era of Preoperative Therapy.

BACKGROUND: Microscopically positive (R1) surgical margins after gastrectomy increase gastric cancer recurrence risk, but optimal management after R1 gastrectomy is controversial. We sought to identify the impact of R1 margins on recurrence patterns and survival in the era of preoperative therapy for gastric cancer. METHODS: Patients who underwent gastrectomy for adenocarcinoma during 1998-2017 at a major cancer center were enrolled. Clinicopathologic factors associated with positive margins were examined, and incidence, sites, and timing of recurrence and survival outcomes were compared between patients with positive and negative margins. RESULTS: Of 688 patients, 432 (63%) received preoperative therapy. Thirty-four patients (5%) had R1 margins. Compared with patients with negative margins, patients with R1 margins more frequently had aggressive clinicopathologic features, such as linitis plastica (odds ratio [OR] 7.79, p < 0.001) and failure to achieve cT downstaging with preoperative treatment (OR 5.20, p = 0.005). The 5 year overall survival (OS) rate was lower in patients with R1 margins (6% vs 60%; p < 0.001), and R1 margins independently predicted worse OS (hazard ratio 2.37, 95% CI 1.51-3.75, p < 0.001). Most patients with R1 margins (58%) experienced peritoneal recurrence, and locoregional recurrence was relatively rare in this group (14%). Median time to recurrence was 8.5 months for peritoneal dissemination and 15.7 months for locoregional recurrence. CONCLUSION: R1 margins after gastrectomy were associated with aggressive tumor biology, high incidence of peritoneal recurrence after a short interval, and poor OS. In patients with R1 margins, re-resection to achieve microscopically negative margins has to be considered with caution.

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.

The learning curve of TaTME for mid-low rectal cancer: a comprehensive analysis from a five-year institutional experience.

BACKGROUND: Transanal total mesorectal excision (TaTME) was introduced in 2009 as a dedicated approach for the treatment of mid-low rectal cancer. We aimed to describe and discuss the learning curve for 121 consecutive TaTME procedures performed by the same team. METHODS: The primary outcome was the number of operations required to decrease the mean operative time (mOT). The secondary outcomes were the number of operations required to decrease the major complication (MC) rate, the anastomotic leakage (AL) rate, the clinical anastomotic failure rate, and the reoperation rate. A cumulative sum (CUSUM) curve analysis was used to identify the inflection points. As an integrative analysis, Bernoulli CUSUM curves, risk-adjusted CUSUM curves based on the observed-expected outcomes, and CUSUM curves targeting results reported in the literature were created. RESULTS: Seventy-one cases were needed to overcome the OT learning curve sufficiently to reach mastery. The MC and reoperation rates started to decrease after the 54th case and further decreased after the 69th case. The AL rate started to decrease after the 27th case and remained stable at 5-5.1%. The comparison between the different phases of the learning curves confirmed these turning points. CONCLUSIONS: TaTME had a learning curve of 71 cases for the mOT, 55-69 cases for MCs and reoperation, and 27 cases for AL. According to our results, attention should be paid during the first part of the learning curve to avoid an increased rate of MCs and AL.

The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review.

BACKGROUND: The gut microbiota (GM) has been proposed as one of the main determinants of colorectal surgery complications and theorized as the "missing factor" that could explain still poorly understood complications. Herein, we investigate this theory and report the current evidence on the role of the GM in colorectal surgery. METHODS: We first present the findings associating the role of the GM with the physiological response to surgery. Second, the change in GM composition during and after surgery and its association with colorectal surgery complications (ileus, adhesions, surgical-site infections, anastomotic leak, and diversion colitis) are reviewed. Finally, we present the findings linking GM science to the application of the enhanced recovery after surgery (ERAS) protocol, for the use of oral antibiotics with mechanical bowel preparation and for the administration of probiotics/synbiotics. RESULTS: According to preclinical and translational evidence, the GM is capable of influencing colorectal surgery outcomes. Clinical evidence supports the application of an ERAS protocol and the preoperative administration of multistrain probiotics/synbiotics. GM manipulation with oral antibiotics with mechanical bowel preparation still has uncertain benefits in right-sided colic resection but is very promising for left-sided colic resection. CONCLUSIONS: The GM may be a determinant of colorectal surgery outcomes. There is an emerging need to implement translational research on the topic. Future clinical studies should clarify the composition of preoperative and postoperative GM and the impact of the GM on different colorectal surgery complications and should assess the validity of GM-targeted measures in effectively reducing complications for all colorectal surgery locations.

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.

Bleeding "sarcomatosis" as a rare presentation of vascular graft-related angiosarcoma: case report and review of the literature.

BACKGROUND: Angiosarcoma is a rare malignant tumor, originating from vascular endothelial cells, accounting for approximatively 1-2% of soft tissue sarcomas. It is characterized by a rapid proliferation and high metastatic potential. Some cases of angiosarcoma are described in association with vascular prosthesis, orthopedic devices and foreign bodies. Hereby, we report a case of a patient treated with the endovascular placement of a PTFE aorto bis-iliac prosthesis for aortic aneurysm, who developed a graft-related angiosarcoma with bone and peritoneal localizations. The peritoneal "sarcomatosis" led to an acute presentation with hemoperitoneum and anemia. We perform a thorough review of the literature summarizing the description of similar cases, their epidemiology and the possibilities for treatment. CASE PRESENTATION: An 84-year-old male with a history of abdominal aortic aneurysm endovascular repair presented to our emergency department complaining with low back pain radiating to the left limb. He underwent a type II endoleak embolization of the aneurysmal sac nine days before. During hospitalization he underwent a spine MRI which documented a vertebral alteration of non-univocal interpretation. Vertebral biopsy was performed revealing groups of cells of uncertain nature. He lately underwent percutaneous L2-L4 arthrodesis. Forty-two days after admission, he developed acute anemia. Emergency laparotomy revealed a massive hemoperitoneum and actively bleeding peritoneal nodules. Abdominal packing was performed, and several nodules were sent for definitive histological examination. After surgery, he developed progressive and severe hypovolemic shock and expired on postoperative day 5. CONCLUSIONS: Angiosarcoma associated with foreign bodies, especially vascular prosthesis, is a very rare entity. In patients who have a history of prosthetic vascular graft placement that present with lumbar pain, osteolytic changes at radiologic imaging or the development of ascites, angiosarcoma should be considered in the differential diagnosis. Despite the poor prognosis, a prompt diagnosis might give access to an adequate treatment planning, with the aim for disease control and increased survival.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy is Safe for Patients with Peritoneal Metastases from Gastric Cancer and May Lead to Gastrectomy.

BACKGROUND: Laparoscopic hyperthermic intraperitoneal chemotherapy (LS-HIPEC) is a novel strategy for patients with gastric adenocarcinoma (GA) metastatic to the peritoneum. We evaluated the safety profile of LS-HIPEC for patients with positive peritoneal cytology (PPC) or carcinomatosis from GA. METHODS: Outcomes were reviewed of patients with stage IV GA with peritoneal involvement who received LS-HIPEC from June 2014 to January 2017. LS-HIPEC included a 60-minute perfusion of mitomycin-C (30 mg) and cisplatin (200 mg) with inflow temperatures of 41-42 °C and outflow temperatures of 39-40 °C. RESULTS: A total of 71 LS-HIPEC procedures were performed in 44 patients. At diagnosis, 68% (n = 30) had carcinomatosis and 32% (n = 14) had isolated PPC. Three patients (7%) underwent LS-HIPEC for intractable ascites. All patients initially received systemic chemotherapy, and 20 patients (45%) received pre-procedural chemoradiotherapy. The median number of LS-HIPEC procedures performed per patient was one (range 1-5 procedures). There were no conversions to laparotomy, two outflow catheter obstructions, and one major (Clavien-Dindo grade III) surgical complication within 30 days. A total of seven postoperative adverse hematologic events (> CTCAE 2) were observed in five patients (11%), without any major renal or gastrointestinal adverse events within 30 days. The median overall length of hospital stay after LS-HIPEC was 2 (range 2-11) days. Eleven patients (25%) underwent secondary gastrectomy following resolution of peritoneal cytology. CONCLUSIONS: Laparoscopic HIPEC is a safe procedure and may be repeated in patients with peritoneal metastases from gastric cancer. Future studies are required to determine the optimal HIPEC regimen and timing relative to systemic therapy to best minimize morbidity.

Ratio-based staging systems are better than the 7th and 8th editions of the TNM in stratifying the prognosis of gastric cancer patients: A multicenter retrospective study.

BACKGROUND: The current and the previous editions of the tumor-node-metastasis (TNM) system for gastric cancer (GC; TNM8 and TNM7) have a high risk of stage-migration bias when the node count after gastrectomy is suboptimal. Hence, they are possibly not the optimal staging systems for GC patients. This study aims to compare the TNM with two systems less affected by the stage-migration bias, namely, the lymph nodes ratio (LNR) and the log odds of positive lymph nodes (LODDS), to assess which one is the best in stratifying the prognosis of GC patients. METHODS: The sample study included 1221 GC patients. Two 7-cluster staging systems based on the combination of pT categories and LNR and LODDS categories (TLNR and TLODDS) were compared with the two last editions of TNM, using the Akaike information criteria, the Bayesian information criteria, and the receiver operating characteristic (ROC) curve graphs. Further validation on an independent sample of 251 patients was carried out. RESULTS: The univariable and multivariable analyses and the ROC curves detected an advantage of the TLNR and TLODDS systems over the TNM. The TLNR and TLODDS showed the best accuracy both in the subgroup of patients with ≥16 nodes examined. The results were confirmed in the validation analysis. CONCLUSIONS: TLNR and TLODDS staging systems should be considered a valid implementation of the TNM for the prognostic stratification of GC patients. If these results are confirmed in further studies, the future implementation of the TNM should consider the introduction of the LNR or the LODDS along with the number of metastatic nodes.

Clinical features and survival of gastric cancer patients with DNA mismatch repair deficiency.

Patients with germline DNA mismatch repair deficiency (dMMR) have an increased risk of gastric cancer. From our institutional database, we identified 12 patients with germline dMMR gastric cancer. Ten patients (83%) underwent surgical resection, with a 5-year overall survival rate of 88%. None of the three patients who received preoperative therapy and five patients with recurrent or metastatic disease experienced a significant response to 5-fluorouracil-based chemotherapy.

The significance of a nineteenth century definition in the era of genomics: linitis plastica.

BACKGROUND: Linitis plastica due to gastric adenocarcinoma is a condition with a long history, but still lacks a standardized definition and is commonly confused with Borrmann type IV, Lauren diffuse, and signet-cell type gastric cancer. The absence of a clear definition is a problem when investigating its biological characteristics and role as a possible independent factor for prognosis. Nevertheless, the biological behavior for linitis plastica, which is unique, may be valuable in risk stratification and have implications for treatment. A definition of linitis plastica based on molecular or genomic criteria could represent a useful starting point for investigating new targeted therapies. MAIN BODY: This literature review of linitis plastica will focus on the current classifications for gastric cancer, illustrating how the concept of linitis plastica relates to them in most cases and identifying a clear and reproducible definition. Moreover, the review will highlight the diagnostic challenges associated with linitis plastica, its prognostic implications, and the therapeutic options available. Future perspectives for its management are also addressed. CONCLUSION: Linitis plastica is a carcinoma with a scirrhous stroma, involving the submucosal and muscular layers of the stomach even in the absence of mucosal alteration. In most cases, the primary cancer cells are signet-ring cells or scattered cells in the context of a poorly differentiated carcinoma. Diagnosis is challenging. Staging should be thorough, including diagnostic laparoscopy in all cases due to the high incidence of peritoneal involvement. The prognostic significance of linitis plastica is still controversial. Curative-intent surgery, when feasible, should be performed, with a multimodality treatment approach. Cancer-stroma interactions are important features of this disease, and represent attaining potential target for future therapies. Future pathologic assessments of gastric cancer should report the stromal reaction in order to allow better characterization of the tumor.

A case report of a giant rectal adenoma causing secretory diarrhea and acute renal failure: McKittrick-Wheelock syndrome.

BACKGROUND: The McKittrick-Wheelock syndrome is a rare depletion syndrome caused by a secretory villous adenoma or a carcinoma of the rectosigmoid tract. An aggressive hydroelectrolyte rebalancing is often needed, and curative treatment is obtained only with complete removal of the lesion, by endoscopy or surgery. Low clinical suspicion often delays the diagnosis, resulting in detrimental complications. CASE PRESENTATION: We report the case of a 75-year-old woman, presenting to the emergency department with acute renal failure and electrolyte imbalance, reporting an history of recurrent episodes of dehydration and chronic diarrhea. After being admitted to the nephrology department she underwent diagnostic investigation that revealed the presence of a giant adenoma of the rectum. The patients received supportive therapy and was subsequently treated with surgery, with a favorable outcome. CONCLUSIONS: A prompt diagnosis plays an important role in the treatment of McKittrick-Wheelock syndrome. We describe a case of this condition in detail and review the related literature, underlining the typical diagnostic features and exploring the possible therapeutic options.

Management of acute diverticulitis in Stage 0-IIb: indications and risk factors for failure of conservative treatment in a series of 187 patients.

Left-sided acute diverticulitis in WSES Stage 0-IIb preferentially undergoes conservative management. However, there is limited understanding of the risk factors for failure of this approach. The aim of this study was to investigate the factors associated with the decision to perform conservative treatment as well as the predictors of its failure. We included patients with a diagnosis of WSES diverticulitis CT-driven classification Stage 0-IIb treated in the Emergency Surgery Unit of the Agostino Gemelli University Hospital Foundation between 2014 and 2020. The endpoints were the comparison between the characteristics and clinical outcomes of acute diverticulitis patients undergoing conservative versus operative treatment. We also identified predictors of conservative treatment failure. A set of multivariable backward logistic analyses were conducted for this purpose. The study included 187 patients. The choice for operative versus conservative treatment was associated with clinical presentation, older age, higher WSES grade, and previous conservative treatment. There were 21% who failed conservative treatment. Of those, major morbidity and mortality rates were 17.9% and 7.1%, respectively. A previously failed conservative treatment as well as a greater WSES grade and a lower hemoglobin value were significantly associated with failure of conservative treatment. WSES classification and hemoglobin value at admission were the best predictors of failure of conservative treatment. Patients failing conservative treatment had non-negligible morbidity and mortality. These results promote the consideration of a combined approach including baseline patients' characteristics, radiologic features, and laboratory biomarkers to predict conservative treatment failure and therefore optimize treatment of acute diverticulitis.

Benefit of a multimodal approach combining chemotherapy and surgery in oligometastatic gastric cancer: experience from a tertiary referral center.

Introduction: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC). Methods: This retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan-Meier method. Prognostic factors were assessed with the Cox model. Results: Data from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8-29.4) and median RFS was 10.6 mo. (95% CI 6.3-14.8). Pathologic response according to the Mandard criteria (TRG 1-3, not reached versus 20.5 mo. for TRG 4-5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series. Discussion: A sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy.

Predicting peritoneal recurrence after radical gastrectomy for gastric cancer: Validation of a prediction model (PERI-Gastric 1 and PERI-Gastric 2) on a Korean database.

BACKGROUND: Peritoneal recurrence is a significant cause of treatment failure after radical gastrectomy for gastric cancer. The prediction of metachronous peritoneal recurrence would have a significantly impact risk stratification and tailored treatment planning. This study aimed to externally validate the previously established PERI-Gastric 1 and 2 models to assess their generalizability in an independent population. METHODS: Retrospective external validation was conducted on a cohort of 8564 patients who underwent elective gastrectomy for stage Ib-IIIc gastric cancer between 1998 and 2018 at the Yonsei Cancer Center. Discrimination was tested using the area under the receiver operating characteristic curves (AUROC). Accuracy was tested by plotting observations against the predicted risk of peritoneal recurrence and analyzing the resulting calibration plots. Clinical usefulness was tested with a decision curve analysis. RESULTS: In the validation cohort, PERI-Gastric 1 and PERI-Gastric 2 exhibited an AUROC of 0.766 (95 % C.I. 0.752-0.778) and 0.767 (95 % C.I. 0.755-0.780), a calibration-in-the-large of 0.935 and 0.700, a calibration belt with a 95 % C.I. over the bisector in the risk range of 24%-33 % and 35%-47 %. The decision curve analysis revealed a positive net benefit in the risk range of 10%-42 % and 15%-45 %, respectively. CONCLUSIONS: This study presents the external validation of the PERI-Gastric 1 and 2 scores in an Eastern population. The models demonstrated fair discrimination and satisfactory calibration for predicting the risk of peritoneal recurrence after radical gastrectomy, even in Eastern patients. PERI-Gastric 1 and 2 scores could also be applied to predict the risk of metachronous peritoneal recurrence in Eastern populations.

Borrmann Type Predicts Response to Preoperative Therapy in Advanced Gastric Cancer.

PURPOSE: The Borrmann classification system is widely used to classify advanced gastric cancer (GC). No studies have focused on the relationship between Borrmann type and response to preoperative therapy. METHODS: Patients with advanced GC who received preoperative therapy followed by curative-intent gastrectomy from September 2016 through September 2021 were identified. Clinicopathologic characteristics were compared by Borrmann type. Logistic regression models were fit to analyze the relationship between Borrmann type and pCR rate. RESULTS: Of the 227 patients who underwent gastrectomy during the period studied, 73 had pretreatment endoscopic images available for analysis. We classified the tumors as follows: Borrmann type 1, 4 (6%); type 2, 17 (23%); type 3, 33 (45%); and type 4, 19 (26%). Nine patients (12%) achieved pCR; 6 of these (67%) had type 1/2 GC and 3 (33%) had type 3. Multivariable logistic regression showed that Borrmann type 3/4 was the only independent factor associated with pCR (odds ratio 0.12; p = 0.023), but 2-year overall survival rates did not differ by Borrmann type (p = 0.216). CONCLUSION: Patients with Borrmann type 3/4 advanced GC have a lower likelihood of achieving pCR after preoperative therapy than those with type 1/2 GC. Determining the Borrmann type preoperatively can guide treatment decision-making.

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.