Complication of Gastric Cancer Surgery: A Single Centre Experience.

BACKGROUND/AIM: Gastric cancer surgery is still characterised by high morbidity and mortality. However, in 2018 an online platform, GASTRODATA has been proposed in Europe to standardize the recording of gastric surgery complications. The aim of the study was to present a single center experience regarding incidence and grading of acute postoperative complications in a population of patients treated surgically for gastric cancer on the basis of the gastrodata online platform. PATIENTS AND METHODS: The present study was a single center, observational, retrospective trial held in the General Surgery Unit of the Sant'Andrea Hospital of Rome. The study included 181 consecutive patients who underwent gastric surgical resection for cancer from May 2004 to December 2020 with curative R0 purpose. RESULTS: Thirty-three percent of patients reported at least one complication, while seventeen percent of the whole population reported a complication classified as at least grade 3 on the Clavien Dindo Classification. The most frequent complications were disorders of the respiratory system (13.3%), followed by bleeding (7.6%) and wound infections (6.2%). Deaths accounted for 3.7% of the population. CONCLUSION: A list of defined complications of gastrectomy, if systematically adopted in the Literature, could lead to a reduction in the wide variation of proposals for treatment and assessment. Objectively evaluating the impact of complications on outcomes can lead to quality improvement project proposals.

Postoperative Pancreatic Fistula: Is Minimally Invasive Surgery Better than Open? A Systematic Review and Meta-analysis.

BACKGROUND/AIM: Minimally invasive pancreaticoduodenectomy (PD) is gaining popularity. The aim of this study was to compare the incidence of postoperative pancreatic fistula (POPF) after minimally invasive versus open procedures. MATERIALS AND METHODS: Following the PRISMA statement, literature research was conducted focusing on papers comparing the incidence of POPF after open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD). RESULTS: Twenty-one papers were included in this meta-analysis, for a total of 4,448 patients. A total of 2,456 patients (55.2%) underwent OPD, while 1,992 (44.8%) underwent MIPD. Age, ASA score III patients, incidence of pancreatic ductal adenocarcinoma and duct diameter were significantly lower in the MIPD group. No statistically significant differences were found between the OPD and MIPD regarding the incidence of major complications (15.6% vs. 17.0%, respectively, p=0.55), mortality (3.7% vs. 2.4%, p=0.81), and POPF rate (14.3% vs. 12.9%, p=0.25). CONCLUSION: MIPD and OPD had comparable rates of postoperative complications, postoperative mortality, and POPF.

The Role of Surgery in the Treatment of Metachronous Liver Metastasis from Gastric Cancer: A Systematic Review.

BACKGROUND: Few data are available regarding metachronous liver metastases from gastric cancer. We aimed to identify data regarding the survival of these patients, considering the chosen treatment, with particular attention to the role of surgery. MATERIALS AND METHODS: A systematic review was carried out from 2000 to 2020. We chose articles reporting data from patients with metachronous liver metastases after curative gastrectomy. Data regarding 1-, 3- and 5-year overall survival were analyzed. RESULTS: Survival was improved in patients eligible for surgery (absence of extrahepatic non-curative factors and feasible complete macroscopic removal of liver deposits, i.e., H1 and H2 liver involvement, metastases less than 5 cm in size) when curative liver resection was performed, with a median overall survival of 24 months (vs. 3.13 in patients treated with chemotherapy). N Status, extent and maximum size of liver metastases, and hepatic surgical treatment were identified as independent prognostic factors. CONCLUSION: Selected patients with metachronous liver metastases from gastric cancer may benefit from multimodal 'aggressive' treatment. When hepatic involvement is limited (H1 and H2) and the size of metastases less than 5 cm, surgery was shown to increase survival.

Distal Pancreatectomy with Celiac Axis Resection: Systematic Review and Meta-Analysis.

BACKGROUND: Major vascular invasion represents one of the most frequent reasons to consider pancreatic adenocarcinomas unresectable, although in the last decades, demolitive surgeries such as distal pancreatectomy with celiac axis resection (DP-CAR) have become a therapeutical option. METHODS: A meta-analysis of studies comparing DP-CAR and standard DP in patients with pancreatic adenocarcinoma was conducted. Moreover, a systematic review of studies analyzing oncological, postoperative and survival outcomes of DP-CAR was conducted. RESULTS: Twenty-four articles were selected for the systematic review, whereas eleven were selected for the meta-analysis, for a total of 1077 patients. Survival outcomes between the two groups were similar in terms of 1 year overall survival (OS) (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.34 to 1.31, p = 0.24). Patients who received DP-CAR were more likely to have T4 tumors (OR 28.45, 95% CI 10.46 to 77.37, p < 0.00001) and positive margins (R+) (OR 2.28, 95% CI 1.24 to 4.17, p = 0.008). Overall complications (OR, 1.72, 95% CI, 1.15 to 2.58, p = 0.008) were more frequent in the DP-CAR group, whereas rates of pancreatic fistula (OR 1.16, 95% CI 0.81 to 1.65, p = 0.41) were similar. CONCLUSIONS: DP-CAR was not associated with higher mortality compared to standard DP; however, overall morbidity was higher. Celiac axis involvement should no longer be considered a strict contraindication to surgery in patients with locally advanced pancreatic adenocarcinoma. Considering the different baseline tumor characteristics, DP-CAR may need to be compared with palliative therapies instead of standard DP.

Left-sided portal hypertension after pancreatoduodenectomy with resection of the portal/superior mesenteric vein confluence. Results of a systematic review.

BACKGROUND: Pancreatoduodenectomy with synchronous resection of the portal vein/superior mesenteric vein confluence may result in the development of left-sided portal hypertension. Left-sided portal hypertension presents with splenomegaly and varices and may cause severe gastrointestinal bleeding. The aim of the study is to review the incidence, treatment, and preventive strategies of left-sided portal hypertension. METHODS: A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify all studies published up to September 30, 2019 reporting data on patients with left-sided portal hypertension after pancreatoduodenectomy with venous resection. RESULTS: Eight articles including 829 patients were retrieved. Left-sided portal hypertension occurred in 7.7% of patients who had splenic vein preservation and 29.4% of those having splenic vein ligation. Fourteen cases of gastrointestinal bleeding owing to left-sided portal hypertension were reported at a mean interval of 28 months from pancreatoduodenectomy. Related mortality at 1 month was 7.1%. Treatment of left-sided portal hypertension consisted of splenectomy in 3 cases (21%) and colectomy in 1 (7%) case, whereas radiologic, endoscopic procedures or conservative treatments were effective in the other cases (71%). CONCLUSION: Left-sided portal hypertension represents a potentially severe complication of pancreatoduodenectomy with venous resection occurring at greater incidence when the splenic vein is ligated and not reimplanted. Left-sided portal hypertension-related gastrointestinal bleeding although rare can be managed depending on the situation by endoscopic, radiologic procedures or operative intervention with low related mortality.

Impact of Anastomotic Leakage on Overall and Disease-free Survival After Surgery for Gastric Carcinoma: A Systematic Review.

BACKGROUND/AIM: Gastric cancer is the fifth most frequently diagnosed cancer and the second most common cause of cancer-related death. The only potentially curative treatment is surgical resection, which is associated with potentially severe complications, such as anastomotic leakage. The aim of this systematic review was to evaluate the relationship between anastomotic leakage and overall and disease-free survival after surgery for gastric cancer. MATERIALS AND METHODS: A systematic literature search was performed and 7 articles published between 2010 and 2019 were included, including a total of 7,167 patients. RESULTS: Among the included studies the frequency of anastomotic leakage ranged from 6 to 41%. Patients affected by anastomotic leakage had an overall survival ranging between 4.1 and 97.6 months, whereas patients who did not experience anastomotic leakage had an overall survival between 23 and 109.5 months. CONCLUSION: Closer follow-up or even more aggressive oncological therapy may be considered for patients affected by anastomotic leakage after surgery for gastric cancer.

Total Pancreatectomy for Pancreatic Carcinoma: When, Why, and What Are the Outcomes? Results of a Systematic Review.

The role of total pancreatectomy (TP) to treat pancreatic carcinoma is still debated. The aims of this study were to systematically review the previous literature and to summarize the indications and results of TP for pancreatic carcinoma. A systematic search was performed to identify all studies published up to November 2018 analyzing the survival of patients undergoing TP for pancreatic carcinoma. Clinical effectiveness was synthetized through a narrative review with full tabulation of results. Six studies published between 2009 and 2016 were retrieved, including 316 patients. The major indication was positive pancreatic margin at frozen section during partial pancreatectomy. The overall morbidity ranged from 36% to 69%, and mortality from 0% to 27%. Overall survival ranged from 52.7% to 67% at 1 year, from 20% to 42% at 3 years of follow-up, whereas the 5-year estimated overall survival ranged from 4.5% to 21.9%. Total pancreatectomy has an important role in the armamentarium of pancreatic surgeons. Postoperative morbidity and mortality are not negligible, but a trend for better postoperative outcomes in recent years is noticed. Mortality related to difficult glycemic control is rare. Long-term survival is comparable with survival after partial pancreatectomy for carcinoma.

In vivo Bioluminescence-Based Monitoring of Liver Metastases from Colorectal Cancer: An Experimental Model.

BACKGROUND: In this study we aimed to develop a new in vivo bioluminescence-based tool to monitor and to quantify colon cancer (CC) liver metastasis development. METHODS: HCT 116 cells were transducted with pLenti6/V5-DEST-fLuc for constitutive expression of firefly luciferase. Infection was monitored analyzing endogenous bioluminescence using the IVIS Lumina II In vivo Imaging System and a positive clone constitutively expressing luciferase (HCT 116-fLuc) was isolated. HCT 116-fLuc cells were left untreated or treated with 1 µM GDC-0449, a Hedgehog pharmacological inhibitor. Moreover, 1 x 106 HCT 116-fLuc cells were implanted via intra-splenic injection in nude mice. Bioluminescence was analyzed in these mice every 7 days for 5 weeks. After that, mice were sacrificed and bioluminescence was analyzed on explanted livers. RESULTS: We found that in vitro bioluminescence signal was significantly reduced when HCT 116-fLuc cells were treated with GDC-0449. Regarding in vivo data, bioluminescence sources consistent with hepatic anatomical localization were detected after 21 days from HCT 116-fLuc intrasplenic injection and progressively increased until the sacrifice. The presence of liver metastasis was further confirmed by ex-vivo bioluminescence analysis of explanted livers. CONCLUSIONS: Our in vitro results suggest that inhibition of Hedgehog pathway may hamper CC cell proliferation and impel for further studies. Regarding in vivo data, we set-up a strategy for liver metastasis visualization, that may allow follow-up and quantification of the entire metastatic process. This cost-effective technique would reduce experimental variability, as well as the number of sacrificed animals.

Recurrence Following Anastomotic Leakage After Surgery for Carcinoma of the Distal Esophagus and Gastroesophageal Junction: A Systematic Review.

BACKGROUND: Esophageal cancer is the ninth most common cancer. The only potentially curative treatment is surgical resection, which unfortunately is still associated with major complications, the most important being anastomotic leakage, currently with an overall rate of up to 26% morbidity. The aim of this systematic review was to evaluate the relationship between anastomotic leakage and recurrence of disease. MATERIALS AND METHODS: A literature search was systematically performed. Seven out of 312 articles dated between 2009 and 2018 fulfilled the selection for a total of 5,433 patients. RESULTS: The frequency of anastomotic leakage ranged from 7.2 to 11.2%. Patients affected by anastomotic leakage had a recurrence rate of 9-56%. CONCLUSION: Closer follow-up or even more aggressive oncological therapy should be considered for patients affected by anastomotic leakage after surgery for carcinoma of the distal esophagus and gastroesophageal junction.

Study of histopathologic parameters to define the prognosis of stage II colon cancer.

PURPOSE: Stage II colon cancer (CC) represents a challenging scenario for the choice of adjuvant chemotherapy; here, histologic factors need to be weighed up to establish the risk of recurrence. Tumor budding (TB) has recently been indicated as a confident predictor of clinical outcome in CC. Likewise, the presence of poorly differentiated clusters (PDCs) in a tumor has been pointed out as a leading criterion of a tumor grading system. Our aim was to evaluate in patients with stage II CC the relationship between these features and clinical outcome. PATIENTS AND METHODS: The study included 174 cases of stage II CC; histopathologic parameters such as TB, PDCs, microsatellite instability (MSI), and CDX2 expression were analyzed. RESULTS: There were 107 (70.9%), 32 (21.2%), and 12 (7.9%) TB scored 1, 2, and 3 respectively; 113 (72.9%), 30 (19.4%), and 12 (7.7%) tumors showed grade 1, 2, and 3 PDCs respectively. A high-MSI was detected in 32 cases (18.4%) while CDX2 was negative in 20 (11.5%) tumor samples. In the whole study population, only the TB was found to be associated with disease-specific survival (P = 0.01). No parameter apart from age (P = 0.04) was a significant prognostic factor for overall survival (P < 0.05). Other commonly reported variables, including tumor size, degree of tumor differentiation, lymphovascular invasion, number of lymph nodes harvested ≥ 12, MSI, and PDCs, were not shown to have significant results. CONCLUSIONS: Although confirmatory studies are awaited, our work supports the role of the TB in defining risk groups of the stage II CC.

Is a Surgical Approach Justified in Metachronous Krukenberg Tumor from Gastric Cancer? A Systematic Review.

BACKGROUND: The treatment of metachronous Krukenberg tumor (mKT) from gastric cancer remains unexplored. We performed a literature review to evaluate whether or not surgical treatment improves survival. METHODS: A systematic review according to PRISMA guidelines was performed. Studies reporting on patients who underwent surgical treatment for mKT from gastric cancer were selected. Metachronous disease was divided as follows: confined to the ovaries, confined to the pelvis, or beyond the pelvis. Outcomes evaluated included overall survival (OS), progression-free survival (PFS), resection rate (R0), and factors predicting survival. RESULTS: 13 retrospective reports fulfilled the selection criteria (512 patients). Most of the patients presented at a premenopausal age. The median presentation interval from gastrectomy ranged from 16 to 21.4 months. Median OS ranged between 9 and 36 months. 1-year OS ranged between 52.5 and 59%, and 3-years OS between 9.8 and 36.5%. Resection margin, peritoneal seeding, and chemotherapy regimen and cycles influenced survival. CONCLUSION: Surgical treatment and adjuvant chemotherapy in patients with mKT from gastric cancer seems to be associated with improved survival and is justified especially in young patients. Disease location and R0 resection should be considered when selecting patients.

Treatment options for PNET liver metastases: a systematic review.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms. About 40-80% of patients with PNET are metastatic at presentation, usually involving the liver (40-93%). Liver metastasis represents the most significant prognostic factor. The aim of this study is to present an up-to-date review of treatment options for patients with liver metastases from PNETs. METHODS: A systematic literature search was performed using the PubMed database to identify all pertinent studies published up to May 2018. RESULTS: The literature search evaluated all the therapeutic options for patients with liver metastases of PNETs, including surgical treatment, loco-regional therapies, and pharmacological treatment. All the different treatment options showed particular indications in different presentations of liver metastases of PNET. Surgery remains the only potentially curative therapeutic option in patients with PNETs and resectable liver metastases, even if relapse rates are high. Efficacy of medical treatment has increased with advances in targeted therapies, such as everolimus and sunitinib, and the introduction of radiolabeled somatostatin analogs. Several techniques for loco-regional control of metastases are available, including chemo- or radioembolization. CONCLUSIONS: Treatment of patients with PNET metastases should be multidisciplinary and must be personalized according to the features of individual patients and tumors.

Evolution of pancreatectomy with en bloc venous resection for pancreatic cancer in Italy. Retrospective cohort study on 425 cases in 10 pancreatic referral units.

INTRODUCTION: The aim of this study is to analyze the evolution of pancreatectomy with venous resection in 10 referral Italian centers in the last 25 years. METHODS: A multicenter database of 425 patients submitted to pancreatectomy with venous resection between 1991 and 2015 was retrospectively analyzed. Patients were classified in 5 periods: 1 (1991-1995); 2 (1996-2000); 3 (2001-2005); 4 (2006-2010); 5 (2011-2015). Indications and outcomes were compared according to the period of surgery. RESULTS: Nineteen patients were operated in period 1, 28 in period 2, 91 in period 3, 140 in period 4, and 147 in period 5. Use of neoadjuvant therapy increased from 0% in period 1 and 2-12.1% in period 5. Postoperative complications ranged from 46.3% to 67.8%, and mortality from 5.3% to 9.2%. Median survival progressively increased, from 6 months in period 1-16 months in period 2, 24 months in period 3 and 4 and 35 months in period 5 (p = 0.004). Period, venous and nodal invasion were significant prognostic factors for survival. CONCLUSION: Management and outcomes of pancreatectomy with venous resection have evolved in the last 25 years in Italy. Improvement in patients' multidisciplinary management has lead to significant improvement of median survival.

Pancreatectomy combined with multivisceral resection for pancreatic malignancies: is it justified? Results of a systematic review.

BACKGROUND: Multivisceral resections combined with pancreatectomy have been proposed in selected patients with tumor invasion into adjacent organs, in order to allow complete tumor resection. Some authors have also reported multivisceral resection combined with metastasectomy in very selected cases. The utility of this practice is debated. The aim of the review is to compare the postoperative results and survival of pancreatectomies combined with multivisceral resections with those of standard pancreatectomies. METHODS: A systematic literature search was performed to identify all studies published up to February 2017 that analyzed data of patients undergoing multivisceral and standard pancreatectomies. Clinical effectiveness was synthetized through a narrative review with full tabulation of results. RESULTS: Three studies were retrieved, including 713 (80%) patients undergoing standard pancreatectomies and 176 (20%) undergoing multivisceral resections (MVR). Postoperative morbidity ranged from 37% to 50% after standard resections and from 56% to 69% after MVR. In-hospital mortality ranged from 4% after standard pancreatectomies to 10% after MVR. Median survival ranged from 20 to 23 months in standard resections and from 12 to 20 months after MVR, without significant differences. DISCUSSION: The current literature suggests that multivisceral pancreatectomies are feasible and may increase the number of completely resected patients. Morbidity and mortality are higher than after standard pancreatectomies, and these procedures should be reserved to selected patients in referral centers. Further studies on the role of neoadjuvant therapy in this setting are advisable.

Can pancreatic cancer be detected by adrenomedullin in patients with new-onset diabetes? The PaCANOD cohort study protocol.

INTRODUCTION: Pancreatic cancer is a leading cause of cancer-related death. Its diagnosis is often delayed and patients are frequently found to have unresectable disease. Patients diagnosed with new-onset diabetes have an 8-fold risk of harboring pancreatic cancer. Adrenomedullin has been claimed to mediate diabetes in pancreatic cancer. New screening tools are needed to develop an early diagnosis protocol. METHODS: Patients aged 45-75 years within 2 years of first fulfilling the ADA criteria for diabetes will be prospectively enrolled in this study. Sepsis, renal failure, microangiopathy, pregnancy, acute heart failure and previous malignancies will be considered as exclusion criteria. RESULTS: 440 patients diagnosed with new-onset diabetes will be enrolled and divided into 2 groups: one with high adrenomedullin levels and one with low adrenomedullin levels. Patients will undergo 3 years' follow-up to detect pancreatic cancer development. CONCLUSIONS: Identifying a marker for pancreatic cancer among high-risk patients such as new-onset diabetics might lead to the identification of a subpopulation needing to be screened in order to enable early diagnosis and treatment of a highly lethal tumor. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on May 25, 2015 under registration number NCT02456051.