Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Association between colorectal cancer and Streptococcus gallolyticus subsp. pasteuranus (former S. bovis) endocarditis: clinical relevance and cues for microbiota science. Case report and review of the literature.

OBJECTIVE: The purpose of this paper is to contextualize the case of a patient with a synchronous diagnosis of colorectal cancer (CRC) and endocarditis from S. gallolyticus subsp. pasteuranus (former S. Bovis) within the current evidence, in order to determine if this condition is indicative of an underlying CRC and if it has any pathophysiologic significance. PATIENTS AND METHODS: First, we describe the clinical case. Then, we review the literature focused on the association between infections from the former S. Bovis group and CRC and on the possible role of certain microbiota species on the occurrence of CRC. At last, we discuss the implications of this case considering the current evidence. RESULTS: There is a strong association between all the species of the former S. Bovis group and CRC. There is initial evidence that these bacteria may contribute to CRC by a genomic passenger mechanism. CONCLUSIONS: There are two main conclusions for this paper. The first one is that CRC neoplasms and endocarditis from all species of the former S. bovis group have a strong association. Any case of infection by these subspecies should prompt to a diagnostic completion by colonoscopy. The second one is that there is an increased need for detailed reports/series and original articles based on the evaluation of gut microbiota in patients with CRC, with the aim to clarify if the association between bacteria and CRC is causative or sporadic and to better understand the possible causative mechanism of specific bacteria in initiating and promoting CRC.

Fashioning enterotomy closure after totally laparoscopic ileocolic anastomosis for right colon cancer: a multicenter experience.

BACKGROUND: Laparoscopic right hemicolectomy is a commonly performed procedure. Little is known on how to perform the enterotomy closure after stapled side-to-side intracorporeal anastomosis. METHOD: A multicentric case-controlled study has been designed to compare different ways to fashion enterotomy closure: double layer versus single layer, sewn versus stapled, and robotic versus laparoscopic approach. Furthermore, additional characteristics including sutures' materials, interrupted versus running suture and the presence of deep corner suture has been investigated. RESULTS: We collected data for 1092 patients who underwent right hemicolectomy at ten centers. We analyzed 176 robotic against 916 laparoscopic anastomosis: no significant differences were found in terms of bleedings (p = 0.455) and anastomotic leak (p = 0.405). We collected data from 126 laparoscopic sewn single-layer versus 641 laparoscopic sewn double-layer anastomosis: a significant reduction was recorded in terms of leaks in double-layer group (p = 0.02). About double-layer characteristics, we found a significant reduction of bleedings (p = 0.008) and leaks (p = 0.017) with a running suture; similarly, a reduction of bleedings (p = 0.001) and leaks (p = 0.005) was observed with the usage of deep corner closure. The presence of a barbed suture thread seemed to significantly reduce both bleedings (p = 0.001) and leaks (p = 0.001). We found no significant differences in terms of bleedings (p = 0.245) and anastomotic leak (p = 0.660) comparing sewn versus stapled anastomosis. CONCLUSIONS: Fashioning a stapled ileocolic intracorporeal anastomosis, we can recommend the adoption of a double-layer enterotomy closure using a running barbed suture in the first layer. Totally, stapled closure and robotic assistance have to be considered a non-inferior alternative.

European Society of Surgical Oncology's strategy for clinical research: Paving the way for a culture of research in cancer surgery.

As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.

3D MRI segmentation and 3D circumferential resection margin evaluation for a standard rectal cancer assessment.

AIM: Recent studies focused on rectal cancer suggested that a 3D imaging segmentation obtained from MRI data could contribute in the definition of the circumferential resection margin (CRM) and in the assessment of the tumor regression following neo-adjuvant treatments. Here, we propose a method for defining and visualizing the circumferential margins using 3D MRI segmentation; this methodology was tested in a clinical study comparing 3D CRM assessment vs standard MRI imaging. PATIENTS AND METHODS: MRI scans performed before neo-adjuvant treatments were selected and reviewed. 3D mesorectal/tumor segmentations were obtained using Digital Imaging and COmmunications in Medicine (DICOM) data; CRMs were calculated using 3D volumes plus a color scale for the closest distances. RESULTS: 3D reconstructions were possible in all selected cases and 3D images implemented by the color scale were positive for immediate CRM visualization. Statistical analyses comparing standard radiology disclosed that the degree of consistency, the reliability of ratings, the correlation and precision were optimal considering the overall cases, but lower in the CRM>0 mm sub-group. CONCLUSIONS: This new method is not inferior comparing standard radiology; moreover, the imaging segmentation we obtained was highly promising and could be helpful in defining a standard CRM measurement, thus it could improve clinical practice.

Does a minimum number of 16 retrieved nodes affect survival in curatively resected gastric cancer?

BACKGROUND: According to the TNM classification, the analysis of 16 or more lymph nodes is required for the appropriate staging of gastric cancer. The aim of this study was to evaluate whether this number of resected lymph nodes also affects survival. METHODS: This was a multicenter retrospective study based on an analysis of 992 patients with gastric adenocarcinoma who underwent curative resection between January 1980 and December 2009. Patients were classified according to the number of resected lymph nodes (<16 and ≥16 lymph nodes), the anatomical extent of lymph node dissection (D2 vs. D1), and the staging criteria of the seventh edition of the UICC/AJCC TNM staging system. Survival estimates were determined by univariate and multivariate analyses. RESULTS: Based on the univariate and multivariate analyses, the resection of 16 or more lymph nodes was associated with significantly better survival [p = 0.002; hazard ratio (HR) (95% confidence interval [CI]): 0.519 (0.345-0.780)]. Patients with a lymph node count <16 had a significantly worse survival rate than patients with a lymph node count ≥16 in the pN0 (p = 0.001), pN1 (p = 0.007) and pN2 (p = 0.001) stages. In the majority of cases, ≥16 lymph nodes were retrieved when D2 dissection was performed. CONCLUSIONS: In gastric cancer the retrieval of less than 16 lymph nodes may cause inaccurate staging and/or inadequate treatment, thus affecting survival rates. These patients should be considered a high-risk group for stage migration and worse survival compared with those who have a retrieval of more than 16 lymph nodes.

cDNA-microarray analysis as a new tool to predict lymph node metastasis in gastric cancer.

BACKGROUND: The aim of the present study was to investigate whether microarray gene expression analysis can be used to predict lymph node status in gastric cancer. METHODS: Twenty-nine patients undergoing gastrectomy for cancer were enrolled and subdivided according to the pathologic nodal involvement of their disease (N+ vs. N0). Molecular profiling was performed by cDNA microarray on tumor tissue and healthy mucosa. Data were processed to identify differently expressed genes. Selected genes were categorized with gene ontology. RESULTS: Compared to healthy gastric mucosa, 52 genes were differently expressed in N+ patients, and 50 genes in N0 patients. Forty-five genes were similarly regulated in N+ and N0 patients, whereas 12 genes were differently expressed between N+ and N0 patients. Seven genes were exclusively expressed in N+ patients: Egr-1 was upregulated; Claudin-18, AKR1C2, Cathepsin E, CA II, TFF 1, and progastricsin were downregulated. Five genes were exclusively expressed in N0 patients: Complement C5 receptor 1, PLA2/VII, and MMP- 9 were upregulated; MAO-A and ID-4 were downregulated. CONCLUSIONS: Microarray analysis could be a valuable tool to identify genes associated with lymph node metastasis in gastric cancer. This technique could improve the selection of patients with locally advanced disease who are candidates for extended lymph node dissection, multimodal treatment options, or alternative therapeutic strategies.

Prognostic implications of the lymph node count after neoadjuvant treatment for rectal cancer.

BACKGROUND: The aim of this study was to investigate the effect of neoadjuvant chemoradiotherapy on the lymph node yield of rectal cancer surgery. METHODS: Data for patients who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from June 1992 to June 2009 were reviewed. The primary outcomes measured were the number of lymph nodes retrieved, their status, and patient survival. RESULTS: In total, 345 patients underwent neoadjuvant chemoradiotherapy followed by surgery, and 95 patients had surgery alone. Neoadjuvant chemoradiotherapy decreased both the median (range) number of lymph nodes retrieved (7 (1-33) versus 12.5 (0-44) respectively; P < 0.001) and the number of positive lymph nodes (0 (0-11) versus 0 (0-16); P = 0.001). After neoadjuvant chemoradiotherapy, the number of retrieved lymph nodes was inversely correlated with tumour regression, and with the interval between treatment and surgery. The 5-year overall and disease-free survival rates were 86.5 and 79.1 per cent respectively. After neoadjuvant therapy, lymph node status was found to be an independent predictor of survival, whereas the number of retrieved lymph nodes did not represent a prognostic factor for either overall or disease-free survival. CONCLUSION: Low lymph node count after neoadjuvant chemoradiotherapy for rectal cancer does not signify an inadequate resection or understaging, but represents an increased sensitivity to the treatment.

Prognostic factors and outcomes in Italian patients undergoing curative gastric cancer surgery.

BACKGROUND: Survival of patients after curative surgical resection for gastric cancer (GC) remains poor, thus emphasizing the need for better definition of prognostic factors to improve the long-term course of disease. METHODS: From 1999 to 2009, 110 patients had curative-intent gastrectomy for adenocarcinoma. Clinicopathological features, Helicobacter pylori infection, dietary habits and lifestyle, and the presence of proinflammatory gene polymorphisms were evaluated. RESULTS: At the end of follow-up, 55 deaths had occurred, 48 of them due to GC, whereas the median overall survival (OS) and disease-free survival (DFS) were 62 and 51 months, respectively. From the Kaplan-Meier analysis and log-rank test, statistically significant differences in OS and DFS were found for tumor site (only for DFS), tumor size, lymph node metastasis ratio (NR), and tumor-node-metastasis stage, but not for age, comorbidity, H. pylori infection, cigarette smoking, and IL1B or TNFA polymorphisms. Multivariable Cox regression analysis revealed NR was an independent prognostic factor for OS and DFS. Cardia tumor and patient age 65 years or older were also independent prognostic factors for OS and DFS. CONCLUSIONS: Tumor-related factors remain strongest predictors of survival in GC patients after surgery. Particularly, NR was an effective feature in identifying patients at high risk for adverse outcome.

Surgical issues after neoadjuvant treatment for gastric cancer.

Gastric carcinoma is one of the most frequent malignancies in the world and its clinical behavior depends on the metastatic potential of the tumour. Particularly, lymphatic metastasis is one of the main predictor of tumour recurrence and survival and current pathologic staging systems reflect the concept that lymphatic spread is the most relevant prognostic factor in patients resected with curative intent. This is deducted by the observation that two thirds of gastric cancers in the western world present at an advanced stage, with nearly 85% of tumors accompanied by lymph node metastasis at diagnosis. To date most therapeutic efforts are directed toward individualization of therapeutic protocols, tailoring the extent of resection integrated by the administration of preoperative and postoperative treatment. The goal of such strategies is to improve prognosis towards the achievement of a curative resection (R0-resection) with minimal morbidity and mortality, with better postoperative quality of life. A brief review of literature about preoperative therapy for gastric carcinoma will be herein illustrated. The rationale and the general drawbacks of preoperative treatments will be both discussed in order to demonstrate its value in terms of safety and efficacy.

Ratio of metastatic lymph nodes: impact on staging and survival of gastric cancer.

AIMS: No consensus exists on the level and number of lymph nodes to be dissected and examined for accurate staging of patients with resectable gastric cancer. The aim of this study was to examine the prognostic value and staging accuracy of the metastatic lymph nodes ratio (NR). METHODS: The postoperative survival of 247 patients with gastric cancer who underwent gastrectomy was analyzed. Lymph nodes status was assigned according to three different classifications: 6th UICC/AJCC TNM; JGCA; NR (NR0: 0%; NR1: < or =20%; NR2: >20%). Staging accuracy of the three classifications was compared according to patients survival. RESULTS: A significant difference in survival was observed in patients with NR1 versus NR2. At multivariate analysis only NR along with pT and grading were found to be independent prognostic factors. Stage migration was present in 84 cases (51%) with JGCA classification, in 30 (19%) with 6th UICC/AJCC TNM classification and in only 18 cases (11%) when NR was applied. CONCLUSIONS: Our data showed that NR is a simply reproducible and highly reliable staging system with a strong ability to predict patients' outcome. Compared to other nodal staging classifications, NR is less influenced from the number of the lymph nodes dissected and examined, reducing the stage migration phenomenon.

A case-control study comparing methylene blue directed biopsies and random biopsies for detecting pre-cancerous lesions in the follow-up of gastric cancer patients.

OBJECTIVES: To compare the accuracy of Methylene Blue (MB) targeted biopsies with random biopsies in detecting intestinal metaplasia and dysplasia in the follow-up of patients after gastrectomy for gastric cancer. METHODS: Thirty patients (21 Billroth II, 9 Billroth 1) for cancer, referred to the Gastroenterology Unit for an elective esophagogastroduodenoscopy (EGD), were enrolled. All endoscopies were performed with a high-resolution videoendoscope with an adjustable image magnification: EG-485ZH (Fujinon, Omiya, Japan). During EGD three random biopsies were taken in the stomach and, after staining with MB, three targeted biopsies were taken from every stained area. RESULTS: In 28 patients traditional endoscopy showed hyperemia of the anastomosis, in 2 patients a lesion. After MB in 6/30 there were stained area (2 lesions seen with traditional endoscopy and 4 blue areas in other patients). As regards histology: 24 patients showed inflammation, while 2 patients with alterations in traditional endoscopy and with MB showed metaplasia and high grade dysplasia. In 4/30 (13.3%) patients MB guided biopsies showed significant lesions (3 intestinal metaplasia, 1 low grade dysplasia) while random biopsies showed only inflammation. CONCLUSIONS: After partial gastrectomy, the mucosa of the residual stomach usually undergoes severe changes, and these lesions are known to be pre-cancerous. The diagnostic accuracy of the MB technique seems to be superior to random biopsies for identification of intestinal metaplasia, dysplasia, and may be helpful in targeting biopsies and early endoscopic treatment.

The role of local excision in rectal cancer after complete response to neoadjuvant treatment.

Correlation between pathological response of primary tumour and mesorectal lymph node involvement was prospectively evaluated to assess the role of local excision (LE) in rectal cancer after complete response to neoadjuvant treatment. A series of 272 consecutive rectal cancer, submitted to neoadjuvant radiochemotherapy (RCT) and surgery with total mesorectal excision (TME) were analysed. Tumour downstaging (pT) and tumour regression grade (TRG) together with sex, age, location of the tumour, pre-treatment clinical stage, type of chemoradiation and operation performed entered in an univariate and multivariate analysis. Pathological complete response on primary tumour was found in 56 patients (20.6%). Lymph node metastases were found in 72 patients (26.5%). The rate of positive nodes was 1.8% for pT0 and TRG1 cases, respectively, to go up to 6.3% for pT1 and 24.1% for TRG 2 cases, respectively. At the univariate analysis, factors with a statistically significant correlation with the risk of lymph node metastasis were: clinical pre-treatment N stage (p<0.05), pT stage (p<0.001) and TRG (p<0.001). At the multivariate analysis, the best predictors of pathologic lymph node involvement were pT stage (p=0.0013 ) and TRG (p=0.0011). Because LE is an adequate technique to assess the tumour pathological response and nodal involvement in pT0 or TRG1 cases seems extremely infrequent, radical resection is probably not justified after pathological complete response. Prospective randomized trials are necessary to establish if, in these cases, LE can guarantee the same oncologic results offered by the currently adopted protocols of RCT followed by radical resections.

Calcitriol plus hydrochlorothiazide prevents transient post-thyroidectomy hypocalcemia.

BACKGROUND: The aim of our double-blinded randomized prospective placebo-controlled study was to test if a week long pre-treatment with hypercalcemic drugs may prevent transient post-thyroidectomy hypocalcemia and reduce hospital stay. METHODS: Forty-two patients undergoing total thyroidectomy were randomized into two groups. Group 1: 22 patients treated with calcitriol 1.5 mcg/die plus hydrochlorothiazide; Group 2: 20 patients only treated with placebo (mineral integrates) as control group. Calcium and PTHi serum levels were assayed baseline and the days before and after thyroidectomy. RESULTS: Baseline calcium and PTHi did not differ between the two groups. Pre-surgery calcemia significantly increased in group 1 (p<0.05) while PTHi significantly decreased (p<0.05). Post-surgery calcemia and PTHi further significantly decreased in both groups, hypocalcemia (<2.10 mmol/l) occurring in 1 out of 22 patients in group 1 without symptoms and in 10 out of 20 in controls (20% developing symptoms) (p<0.01). The hospital stay resulted significantly shorter in group 1 (2.4+/-0.6 days) in respect to the control group (3.6+/-1.4 days, p<0.05). CONCLUSION: The administration of calcitriol plus hydrochlorothiazide is able to prevent transient post-thyroidectomy hypocalcemia and to reduce hospital stay.

Response to neoadjuvant chemotherapy and effects of tumor regression in gastric cancer.

AIMS: Aim of this study is the evaluation of the effects induced by neoadjuvant chemotherapy (NACT) and its impact on survival on a series of locally advanced gastric carcinomas. METHODS: Downstaging was assessed comparing pre-treatment clinical and laparoscopic staging with post-operative pathologic staging on 30 consecutive patients who completed a 3-year follow-up. Tumor downstaging and the grade of pathologic response were included in a statistical correlation between tumor regression induced by NACT and 3-year survival. RESULTS: In this series tumor downstaging was obtained in 13 out of 30 patients. After the completion of 3-year follow-up, overall survival was >37.5months with an overall survival rate of 56.7%; this figure reached up to 70.8% in those cases who benefited from a R0-resection (24/30 patients: R0-resection rate 80.0%). CONCLUSIONS: In this study the 3-year survival for locally advanced gastric cancer treated by NACT prior to "D2" surgical resection, compares favourably with historical series treated by surgery alone. Patients who obtained T-downstaging and subsequently benefited from a R0-resection had a definitely better chance of cure, according to a complete 3-year follow-up.

[Clinical significance and prognostic value of tumor maximum diameter in gastric carcinoma]. / Significatività clinica e valore prognostico del diametro massimo del tumore nel carcinoma gastrico.

Maximum tumor diameter (MTD) is considered by many authors as an important prognostic factor in gastric cancer and, in some series, is reported to be strongly correlated with depth of infiltration. Aim of this study was to evaluate the prognostic value of tumor diameter in a monoistitutional series of 153 gastric cancer patients. The Spearman correlation coefficient was also calculated between MTD and other known prognostic factors. For statistical analysis, patients were grouped as follows: MTD 1, < or = 40 mm, and MTD2, > 40 mm. In our series, MTD resulted significantly linked to survival at univariate analysis (p = 0.0001), but multivariate analysis did not evidence MTD as an independent prognostic indicator. The Spearman correlation test documented that MTD2 is strongly correlated with tumor depth (pT), nodal status (pN) and p-stage (p < 0.01) and is a good predictor of locally advanced stage. This retrospective study showed that patients with larger tumor are at an increased risk for tumor advancement and, therefore, MTD could represent a useful parameter for choosing the most appropriate therapeutic strategy.

[Ratio of lymph node metastasis in gastric carcinoma after D2 gastrectomy]. / La ratio dei linfonodi metastatici nel carcinoma gastrico dopo gastrectomia D2.

The classification of lymph node metastasis in patients with gastric carcinoma is controversial. In the past, all systems used for this disease defined N classification by the location of lymph node metastases relatively to the primary tumor. In the 1997, the UICC and AJCC redefined the pathologic nodal status on the basis of the number of involved nodes rather than their location. More recently, the ratio between the number of metastatic and the total examined lymph nodes has been proposed as a new quantitative staging system. Aim of our study was to clarify the outcome of the ratio of the metastatic lymph nodes (RML) in a monoinstitutional series of 164 patient with primary gastric cancer who underwent gastrectomy with D2 lymph node dissection. Our data showed that ratio of metastatic lymph nodes is a simple, convenient, and reproducible staging system with an ability to predict surgical results and it is an independent prognostic factor after D2-gastrectomy.

[T-downstaging after neoadjuvant chemotherapy in locally advanced gastric carcinoma]. / T-downstaging dopo chemioterapia neoadiuvante nel carcinoma gastrico localmente avanzato.

Only a limited number of trials on neoadjuvant chemotherapy for resectable advanced gastric cancer have been planned or conducted up to date, still in recent years this treatment strategy has been considered by many the most promising tool in order to improve survival of locally advanced tumors of the stomach. Aim of this study is to evaluate the clinical significance and the possible impact on survival of tumor downstaging after neoadjuvant chemotherapy followed by D2-gastrectomy in an accurately staged and thoroughly selected group of 30 locally advanced gastric cancer patients, with a complete follow-up of at least 3 years. In our series, T-downstaging was observed in 43.3% of patients; this parameter, along with other known prognostic factors, was found to be significantly associated with survival (p <0.05). Moreover, T-downstaging induced by preoperative chemotherapy was significantly associated with absence of residual tumor (R0) and no lymph node metastases (ypN0) (p <0.05). At multivariate analysis, R0-resection was the only independent prognostic factor (HR 9.439, p <0.0001). According to our results we feel encouraged to consider neoadjuvant chemotherapy a promising modality for increasing the R0-percentage by tumor downstaging.