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BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.
Subject(s)
Consensus , Delphi Technique , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/therapy , Neoplasm Metastasis , Italy , Neoplasm StagingABSTRACT
AIM: Several methods for assessing anastomotic integrity have been proposed, but the best is yet to be defined. The aim of this study was to compare the different methods to assess the integrity of colorectal anastomosis prior to ileostomy reversal. METHOD: A retrospective cohort analysis on patients between 1 January 2010 and 31 December 2020 with a defunctioning stoma for middle and low rectal anterior resection was performed. A propensity score matching comparison between patients who underwent proctoscopy alone and patients who underwent proctoscopy plus any other preoperative method to assess the integrity of colorectal anastomosis prior to ileostomy reversal (transanal water-soluble contrast enema via conventional radiology, transanal water-soluble contrast enema via CT, and magnetic resonance) was performed. RESULTS: The analysis involved 1045 patients from 26 Italian referral colorectal centres. The comparison between proctoscopy alone versus proctoscopy plus any other preoperative tool showed no significant differences in terms of stenoses (p = 0.217) or leakages (p = 0.103) prior to ileostomy reversal, as well as no differences in terms of misdiagnosed stenoses (p = 0.302) or leakages (p = 0.509). Interestingly, in the group that underwent proctoscopy and transanal water-soluble contrast enema the comparison between the two procedures demonstrated no significant differences in detecting stenoses (2 vs. 0, p = 0.98), while there was a significant difference in detecting leakages in favour of transanal water-soluble contrast enema via CT (3 vs. 12, p = 0.03). CONCLUSIONS: We can confirm that proctoscopy alone should be considered sufficient prior to ileostomy reversal. However, in cases in which the results of proctoscopy are not completely clear or the surgeon remains suspicious of an anastomotic leakage, transanal water-soluble contrast enema via CT could guarantee its detection.
Subject(s)
Rectal Neoplasms , Surgical Oncology , Humans , Proctoscopy , Ileostomy/methods , Retrospective Studies , Constriction, Pathologic/surgery , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/surgery , Enema/methods , Contrast Media , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Anastomotic Leak/diagnostic imaging , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Water , ItalyABSTRACT
OBJECTIVE: To gain insight in global practice of RAMIG and evaluated perioperative outcomes using an international registry. BACKGROUND: The techniques and perioperative outcomes of robot-assisted minimally invasive gastrectomy (RAMIG) for gastric cancer vary substantially in literature. METHODS: Prospectively registered RAMIG-cases for gastric cancer (≥10 per center) were extracted from 25 centers in Europe, Asia and South-America. Techniques for the resection, reconstruction, anastomosis and lymphadenectomy were analyzed, and related to perioperative surgical and oncological outcomes. Complications were uniformly defined by the Gastrectomy Complications Consensus Group. RESULTS: Between 2020-2023, 759 patients underwent total (n=272), distal (n=465) or proximal (n=22) gastrectomy (RAMIG). After total gastrectomy with Roux-en-Y-reconstruction, anastomotic leakage rates were 8% with hand-sewn (n=9/111) and 6% with linear stapled anastomoses (n=6/100). After distal gastrectomy with Roux-en-Y (67%) or Billroth-II-reconstruction (31%), anastomotic leakage rates were 3% with linear stapled (n=11/433) and 0% with hand-sewn anastomoses (n=0/26). Extent of lymphadenectomy consisted of D1+ (28%), D2 (59%) or D2+ (12%). Median nodal harvest yielded 31 nodes [IQR 21-47] after total and 34 nodes [IQR 24-47] after distal gastrectomy. R0-resection rates were 93% after total and 96% distal gastrectomy. Hospital stay was 9 days after total and distal gastrectomy, and was 3 days shorter without perianastomotic drains versus routine drain placement. Postoperative 30-day mortality was 1%. CONCLUSIONS: This large multicenter study provided a worldwide overview of current RAMIG-techniques with their respective perioperative outcomes. These outcomes demonstrated high surgical quality, set a quality standard for RAMIG and can be considered an international reference for surgical standardization.
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BACKGROUND: This study evaluated the efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy as a bidirectional approach for gastric cancer (GC) patients with synchronous peritoneal metastases (SPM). METHODS: A retrospective analysis of a prospective PIPAC database was queried for patients who underwent a bidirectional approach between October 2019 and April 2022 at two high-volume GC surgery units in Italy (Verona and Siena). Surgical and oncological outcomes were analyzed. RESULTS: Between October 2019 and April 2022, 74 PIPAC procedures in 42 consecutive patients with Eastern Cooperative Oncology Group performance status ≤2 were performed-32 patients treated in Verona and 10 in Siena. Twenty-seven patients (64%) were female and median age at first PIPAC was 60.5 years (I-III quartiles: 49-68 years). Median Peritoneal Cancer Index (PCI) was 16 (I-III quartiles: 8-26) and 25 patients (59%) had at least two PIPAC procedures. Major complications according to the Common Terminology Criteria for Adverse Events (CTCAE; 3 and 4) occurred in three (4%) procedures, and, according to the Clavien-Dindo classification (>3a), one (1%) severe complication occurred. There were no reoperations or deaths within 30 days. Median overall survival (mOS) from diagnosis was 19.6 months (range 14-24), and mOS from first PIPAC was 10.5 months (range 7-13). Excluding cases with very heavy metastatic peritoneal burden, with PCI from 2 to 26, treated with more than one PIPAC, mOS from diagnosis was 22 months (range 14-39). Eleven patients (26%) underwent curative-intent surgery after a bidirectional approach. R0 was achieved in nine (82%) patients and complete pathological response was obtained in three (27%) cases. CONCLUSIONS: Patient selection is associated with bidirectional approach efficacy and feasibility for SPM GC treatment, which may allow potentially curative surgical radicalization in highly selected cases.
Subject(s)
Peritoneal Neoplasms , Stomach Neoplasms , Humans , Female , Middle Aged , Male , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Cisplatin/therapeutic use , Peritoneal Neoplasms/secondary , Doxorubicin , Retrospective Studies , Prospective Studies , AerosolsABSTRACT
BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed â§12, and proximal and distal free resection margins length ⧠5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.
Subject(s)
Colon, Transverse , Colonic Neoplasms , Laparoscopy , Surgical Oncology , Humans , Colon, Transverse/surgery , Laparoscopy/methods , Treatment Outcome , Retrospective Studies , Colonic Neoplasms/surgery , Postoperative Complications/surgery , Minimally Invasive Surgical ProceduresABSTRACT
BACKGROUND: Identification of reliable risk-stratification tools is critical for surgical decision making, particularly in frail and elderly. The aim of the study is to validate the Emergency Surgery Frailty Index (EmSFI), in over 65 years old patients operated on for acute appendicitis. METHODS: An observational study was conducted enrolling elderly patients with diagnosis of acute appendicitis who underwent emergency appendicectomy or right colectomy, between 2016 and 2021. All patients were treated according to the last SIFIPAC/WSES/SICG/SIMEU guidelines. RESULTS: Overall, 61 patients were analyzed. Complication rate was higher for patients in the second EmSFI risk Class. Moreover, ROC analyses identified 3 as the best cutoff value in predicting risk of adverse postoperative events. Complication rate was higher in oldest elderly patients-over 80 years-(42.9 vs 22.5%; p 0.05) and was mainly related to medical complications (42.9 vs 12.5%, p 0.007). However, intestinal obstruction, peri-appendicular abscess on preoperative CT, peritonitis and a longer duration of surgery are related with increased risk of complications in the group of patients under 80 years. CONCLUSION: The EmSFI score results a valid prognostic marker for frailty status, and it may support the surgeon in emergency setting for acute appendicitis. Patients aged 80 years or older have a higher risk of complications, independent from those factors which relate to increased morbidity in younger elderly patients. Age alone is not a reliable indicator of the real surgical risk, but it must encourage the adoption of multidisciplinary collaborative models of care for this group of patients.
Subject(s)
Appendicitis , Frailty , Aged , Humans , Appendicitis/complications , Appendicitis/diagnosis , Appendicitis/surgery , Frailty/complications , Frailty/diagnosis , Prognosis , Risk Factors , Colectomy/adverse effects , Acute Disease , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Frail ElderlyABSTRACT
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.
Subject(s)
Radiology, Interventional , Stomach Neoplasms , Consensus , Humans , Italy , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/therapy , Tomography, X-Ray ComputedABSTRACT
AIM: The optimal surgical treatment for anatomical anal stenosis (AS) remains to be determined. The aim of this study was to determine the rates of complications and recurrence after anoplasty for anatomical AS and, wherever feasible, compare the outcomes for the various techniques. METHOD: A PROSPERO-registered systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medline, PubMed, Embase, Cochrane Library of Systematic Review, Scopus and Web of Science were searched for articles published up to May 2021. Studies that assessed the outcomes of anoplasty in adult patients with anatomical AS were selected. The primary outcomes were complications and recurrence. The methodological quality of studies was appraised using the Joanna Briggs Institute critical appraisal tools. RESULTS: From the total of 2705 unique screened records, 151 were assessed for eligibility. Only 29 studies (two prospective) met the inclusion criteria, reporting data on 556 patients [mean age 53 (18-83) years, 46% female]. Previous history of surgery for haemorrhoidal disease accounted for three quarters of cases. A total of 14 types of anoplasty were found, with the Y-V flap being the most performed technique [27% of cases (n = 149)]. Complications frequently occurred, with a pooled prevalence of 10.2% (95% CI 3.9%-24.1%) after Y-V flap and 11.5% (5.3%-23.0%) after rhomboid/diamond flap. Patients undergoing house flap achieved better results in terms of clinical improvement, satisfaction and quality of life compared with Y-V flap and rhomboid/diamond flap. When considering only studies with at least 12 months of follow-up, the pooled prevalence of recurrence was 4.7% (2.2%-9.8%), with significantly higher rates observed in the prospective versus retrospective series [pooled prevalence 18.9% (11.5%-29.5%) vs. 3.6% (1.7-7.8%), respectively; p < 0.001]. CONCLUSION: Both complications and recurrence were significantly lower after house flap compared with rhomboid/diamond and Y-V flap. Better designed multicentre studies with longer follow-up are needed to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42021239493.
Subject(s)
Anorectal Malformations , Quality of Life , Adult , Female , Humans , Male , Middle Aged , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Diamond , Prospective Studies , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Familial intestinal gastric cancer (FIGC) remains genetically unexplained and without testing/clinical criteria. Herein, we characterised the age of onset and disease spectrum of 50 FIGC families and searched for genetic causes potentially underlying a monogenic or an oligogenic/polygenic inheritance pattern. METHODS: Normal and tumour DNA from 50 FIGC probands were sequenced using Illumina custom panels on MiSeq, and their respective germline and somatic landscapes were compared with corresponding landscapes from sporadic intestinal gastric cancer (SIGC) and hereditary diffuse gastric cancer cohorts. RESULTS: The most prevalent phenotype in FIGC families was gastric cancer, detected in 138 of 208 patients (50 intestinal gastric cancer probands and 88 unknown gastric cancer histology relatives), followed by colorectal and breast cancers. After excluding benign and intronic variants lacking impact in splicing, 12 rare high-quality variants were found exclusively in 11 FIGC probands. Only two probands carried potentially deleterious variants, but lacked somatic second-hits, weakly supporting the monogenic hypothesis for FIGC. However, FIGC probands developed gastric cancer at least 10 years earlier and carried more TP53 germline common variants than SIGC (p=4.5E-03); FIGC and SIGC could be distinguished by specific germline and somatic variant profiles; there was an excess of FIGC tumours presenting microsatellite instability (38%); and FIGC tumours displayed significantly more somatic common variants than SIGC tumours (p=4.2E-06). CONCLUSION: This study proposed the first data-driven testing criteria for FIGC families, and supported FIGC as a genetically determined, likely polygenic, gastric cancer-predisposing disease, with earlier onset and distinct from patients with SIGC at the germline and somatic levels.
Subject(s)
Genetic Predisposition to Disease , Multifactorial Inheritance/genetics , Stomach Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Adult , Age of Onset , Aged , Aged, 80 and over , Female , Germ-Line Mutation/genetics , Humans , Male , Middle Aged , Pedigree , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: Chronological age per se cannot be considered a prognostic risk factor for outcomes after elective surgery, whereas frailty could be. A simple and easy-to-get marker for frailty, such as handgrip strength (HGS), may support the surgeon in decision for an adequate healthcare plan. AIMS: The aims of this study were to: (1) determine the prevalence of frailty in an abdominal surgery setting independent of age; (2) evaluate the predictive validity of HGS for the length of hospital stay (LOS). METHODS: This is a retrospective study conducted in subjects who underwent abdominal surgical procedures. Only subjects with complete cognitive, functional, nutritional assessments and available measurement of HGS at admission were included. A final cohort of 108 patients were enrolled in the study. RESULTS: Subjects had a mean age of 67.8 ± 15.8 years (age range 19-93 years old) and were mostly men. According to Fried's criteria, 17 (15.7%, 4F/13 M) were fit, 58 (23.7%; 24F/34 M) were pre-frail and 33 (30.6%; 20F/13 M) were frail. As expected, HGS significantly differed between groups having frail lower values as compared with pre-frail and fit persons (fit: 32.99 ± 10.34 kg; pre-frail: 27.49 ± 10.35 kg; frail: 15.96 ± 9.52 kg, p < 0.0001). A final regression analysis showed that HGS was significantly and inversely associated with LOS (p = 0.020) independent of multiple covariates, including age. DISCUSSION: Most of the population undergoing abdominal surgery is pre-frail or frail. The measurement of handgrip strength is simple and inexpensive, and provides prognostic information for surgical outcomes. Muscle strength, as measured by handgrip dynamometry, is a strong predictor of LOS in a surgical setting.
Subject(s)
Frailty , Aged , Aged, 80 and over , Female , Frail Elderly , Frailty/diagnosis , Hand Strength , Humans , Length of Stay , Male , Retrospective StudiesABSTRACT
BACKGROUND: Near-infrared fluorescence image-guided surgery helps surgeons to see beyond the classical eye vision. Over the last few years, we have witnessed a revolution which has begun in the field of image-guided surgery. PURPOSE, AND RESEARCH DESIGN: Fluorescence technology using indocyanine green (ICG) has shown promising results in many organs, and in this review article, we wanted to discuss the 6 main domains where fluorescence image-guided surgery is currently used for esophageal and gastric cancer surgery. STUDY SAMPLE AND DATA COLLECTION: Visualization of lymphatic vessels, tumor localization, fluorescence angiography for anastomotic evaluation, thoracic duct visualization, tracheal blood flow analysis, and sentinel node biopsy are discussed. CONCLUSIONS: It seems that this technology has already found its place in surgery. However, new possibilities and research avenues in this area will probably make it even more important in the near future.
Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Surgery, Computer-Assisted , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Fluorescence , Humans , Indocyanine Green , Sentinel Lymph Node Biopsy/methods , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgeryABSTRACT
INTRODUCTION: Fluorescence imaging of sentinel node biopsy in melanoma is a novel method. Both indocyanine green (ICG) and methylene blue (MB) have fluorescent properties. The aim of this study was to present, for the first time in a clinical series of patients, the possible usage of MB as a fluorescent dye for sentinel node biopsy during surgery for melanoma. MATERIAL AND METHODS: Twenty patients with skin melanoma, who were candidates for sentinel node biopsy were enrolled in our study. All patients underwent simultaneous use of standard nanocolloid and blue dye. Transcutaneous visualization of the sentinel node, visualization of lymphatic channels as well as sentinel node fluorescent visualization were all measured. We also performed calculations of Signal to Background ratios (SBR). RESULTS: In 15% (3/20) of patients, the fluorescent sentinel node was visible through the skin. The median SBR for the sentinel node visualization by fluorescence was 3.15 (range, 2.7-3.5). Lymphatic channels were visible in lymphatic tissue via fluorescence before visualization by the naked eye in 4 patients (20%). The median SBR ratio was 3.69 (range, 2.7-4.2). Sentinel nodes were visible by fluorescence in 13 cases (65%). The median SBR ratio was 2.49 (range, 1.5-5.7). No factors were found to be associated with fluorescent MB visualization of a sentinel node during biopsy. CONCLUSION: This is the first clinical study presenting the usefulness of fluorescent sentinel node biopsy in melanoma patients using MB as a fluorophore. Further studies are necessary to provide methods for its' clinical implementation.
Subject(s)
Melanoma , Sentinel Lymph Node Biopsy , Coloring Agents , Fluorescence , Fluorescent Dyes , Humans , Indocyanine Green , Lymph Nodes/pathology , Melanoma/diagnostic imaging , Melanoma/pathology , Melanoma/surgery , Methylene Blue , Optical Imaging , Sentinel Lymph Node Biopsy/methodsABSTRACT
BACKGROUND: The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. METHODS: The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. RESULTS: A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022). CONCLUSIONS: In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Stomach Neoplasms , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Hyperthermic Intraperitoneal Chemotherapy , Italy , Middle Aged , Peritoneal Neoplasms/drug therapy , Retrospective Studies , Stomach Neoplasms/therapy , Survival RateABSTRACT
Gastric cancer is one of the most common malignancy worldwide. In unresectable or metastatic disease, the prognosis is poor and in generally less than a year. HER2 expression remains an important biomarker to lead the addition of trastuzumab to first-line systemic chemotherapy in unresectable or metastatic gastroesophageal adenocarcinoma. To date, a major issue is represented by resistance to trastuzumab developed during treatment, considering the not improved outcomes in this molecular subtype of gastroesophageal adenocarcinoma to other HER2 target strategies. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance to HER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Furthermore, we describe the prognostic value of new non-invasive screening methods, under development novel agents (e.g., HER2 antibody-drug conjugates and bispecific antibodies) and strategies with antitumor activity in early studies.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Drug Resistance, Neoplasm/genetics , Receptor, ErbB-2/metabolism , Stomach Neoplasms/genetics , Trastuzumab/therapeutic use , Biomarkers, Tumor/genetics , Humans , Prognosis , Stomach Neoplasms/drug therapyABSTRACT
BACKGROUND: The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery. METHODS: It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences. RESULTS: Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment. CONCLUSION: The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with "radical oncological intent", that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Stomach Neoplasms , Humans , Italy/epidemiology , Peritoneal Neoplasms/surgery , Prognosis , Prospective Studies , Retrospective Studies , Stomach Neoplasms/surgeryABSTRACT
BACKGROUND: The incidence of cholelithiasis has been shown to be higher for patients after gastrectomy than for the general population, due to vagal branch damage and gastrointestinal reconstruction. The aim of this trial was to evaluate the need for routine concomitant prophylactic cholecystectomy (PC) during gastrectomy for cancer. METHODS: A multicenter, randomized, controlled trial was conducted between November 2008 and March 2017. Of the total 130 included patients, 65 underwent PC and 65 underwent standard gastric surgery only for curable cancers. The primary endpoint was cholelithiasis-free survival after gastrectomy for gastric adenocarcinoma. Cholelithiasis was detected by ultrasound exam. RESULTS: After a median follow-up of 62 months, eight patients (12.3%) in the control group developed biliary abnormalities (four cases of gallbladder calculi and four cases of biliary sludge), with only three (4.6%) being clinically relevant (two cholecystectomies needed, one acute pancreatitis). One patient in the PC group had asymptomatic biliary dilatation during sonography after surgery. The cholelithiasis-free survival did not show statistical significance between the two groups (P = 0.267). The number needed to treat with PC to avoid reoperation for cholelithiasis was 1:32.5. CONCLUSIONS: Concomitant PC during gastric surgery for malignancies, although reducing the absolute number of biliary abnormalities, has no significant impact on the natural course of patients.
Subject(s)
Adenocarcinoma/mortality , Cholecystectomy/mortality , Cholelithiasis/prevention & control , Gastrectomy/mortality , Stomach Neoplasms/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Survival Rate , Young AdultABSTRACT
BACKGROUND: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. METHODS: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. RESULTS: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72-11.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04-31.4, p = 0.045). CONCLUSIONS: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement.
Subject(s)
Antineoplastic Agents/administration & dosage , Gastrectomy/methods , Stomach Neoplasms/therapy , Cohort Studies , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Progression-Free Survival , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathology , Survival RateABSTRACT
BACKGROUND: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. METHODS: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. RESULTS: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. CONCLUSION: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.
Subject(s)
Delphi Technique , Gastrectomy/adverse effects , Intraoperative Complications , Postoperative Complications , Stomach Neoplasms/surgery , Consensus , HumansABSTRACT
Recent studies have reported germline CDH1 mutations in cases of lobular breast cancer (LBC) not associated with the classical hereditary diffuse gastric cancer syndrome. A multidisciplinary workgroup discussed genetic susceptibility, pathophysiology and clinical management of hereditary LBC (HLBC). The team has established the clinical criteria for CDH1 screening and results' interpretation, and created consensus guidelines regarding genetic counselling, breast surveillance and imaging techniques, clinicopathological findings, psychological and decisional support, as well as prophylactic surgery and plastic reconstruction. Based on a review of current evidence for the identification of HLBC cases/families, CDH1 genetic testing is recommended in patients fulfilling the following criteria: (A) bilateral LBC with or without family history of LBC, with age at onset <50 years, and (B) unilateral LBC with family history of LBC, with age at onset <45 years. In CDH1 asymptomatic mutant carriers, breast surveillance with clinical examination, yearly mammography, contrast-enhanced breast MRI and breast ultrasonography (US) with 6-month interval between the US and the MRI should be implemented as a first approach. In selected cases with personal history, family history of LBC and CDH1 mutations, prophylactic mastectomy could be discussed with an integrative group of clinical experts. Psychodecisional support also plays a pivotal role in the management of individuals with or without CDH1 germline alterations. Ultimately, the definition of a specific protocol for CDH1 genetic screening and ongoing coordinated management of patients with HLBC is crucial for the effective surveillance and early detection of LBC.