Pancreatojejunostomy: standing on the shoulders of giants. A single centre retrospective analysis.

Gaining experience in pancreatic surgery could be demanding especially when minimally invasive approach is used. Pancreatojejunostomy (PJ) is one of the most critical steps during pancreatoduodenectomy (PD). Our aim was to investigate the impact of a surgeon's experience in performing PJ, especially in a subgroup of patients undergoing laparoscopic PD (LPD). Data of consecutive patients undergoing PD from 2017 to 2022 were prospectively collected and retrospectively analyzed. Patients were divided into two groups: M group included patients in which PJ was performed by an experienced surgeon, D group included those receiving PJ by a less experienced one. The groups were compared in terms of postoperative outcomes. 187 patients were selected (157 in group M and 30 in group D). The cohorts differed in terms of median age (68 vs 74 years, p = 0.016), and previous abdominal surgery (41.4% vs 66.7%, p = 0.011), while no difference was found regarding risk of postoperative pancreatic fistula (POPF). The groups did not differ in terms of surgical outcomes. POPF rate was 15.9% and 10% in the M and D group (p = 0.578), respectively. Among patients undergoing laparoscopic PJ POPF rate was 16.0% and 17.7% in the M and D group (p = 0.867), respectively, without difference. No difference was found in terms of POPF in patients undergoing PD independently from the surgeon who performed the PJ, even during LPD. Moderate/high FRS, BMI > 30 kg/m2 and male sex, but not the surgeon who performed the PJ anastomosis, were independent predictors of POPF.

Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma.

BACKGROUND: Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy. METHODS: A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS. RESULTS: The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34). CONCLUSIONS: At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.

Sarcopenia and Patient's Body Composition: New Morphometric Tools to Predict Clinical Outcome After Ivor Lewis Esophagectomy: a Multicenter Study.

BACKGROUND: The impact of preoperative body composition as independent predictor of prognosis for esophageal cancer patients after esophagectomy is still unclear. The aim of the study was to explore such a relationship. METHODS: This is a multicenter retrospective study from a prospectively maintained database. We enrolled consecutive patients who underwent Ivor-Lewis esophagectomy in four Italian high-volume centers from May 2014. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), and subcutaneous fat area (SFA) were determined based on CT images. Perioperative variables were systematically collected. RESULTS: After exclusions, 223 patients were enrolled and 24.2% had anastomotic leak (AL). Sixty-eight percent of patients were sarcopenic and were found to be more vulnerable in terms of postoperative 90-day mortality (p = 0.028). VFA/TAMA and VFA/SFA ratios demonstrated a linear correlation with the Clavien-Dindo classification (R = 0.311 and 0.239, respectively); patients with anastomotic leak (AL) had significantly higher VFA/TAMA (3.56 ± 1.86 vs. 2.75 ± 1.83, p = 0.003) and VFA/SFA (1.18 ± 0.68 vs. 0.87 ± 0.54, p = 0.002) ratios. No significant correlation was found between preoperative BMI and subsequent AL development (p = 0.159). Charlson comorbidity index correlated significantly with AL (p = 0.008): these patients had a significantly higher index (≥ 5). CONCLUSION: Analytical morphometric assessment represents a useful non-invasive tool for preoperative risk stratification. The concurrent association of sarcopenia and visceral obesity seems to be the best predictor of AL, far better than simple BMI evaluation, and potentially modifiable if targeted with prehabilitation programs.

A national survey on the current status of minimally invasive gastric practice on behalf of GIRCG.

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach.

Esophageal Cancer with Early Onset in a Patient with Cri du Chat Syndrome.

BACKGROUND: In Cri du Chat (CdC), cancer as comorbidity is extremely rare. In databases from Denmark, Spain, Australia, New Zealand, and Japan, no cancer was reported; in Italy and Germany, four cancers were identified out of 321 CdCs. METHODS: In a 29-year-old CdC patient, clinical investigations following hematemesis led to the diagnosis of esophageal adenocarcinoma (EAC). A high pain threshold was also observed. Conventional and molecular cytogenetic defined the size of the deletion, and exome analysis on the trio completed the molecular work. RESULTS: Cytogenetic analysis showed a de novo chromosomal alteration: 46,XY,ishdel(5)(p14.3)(D5S28-) and arr[GRCh37] 5p15.33p14.3(1498180_19955760)x1. A quantitative sensory test demonstrated a high heat threshold. A 18f-fluorodeoxyglucose PET/TC scan of the brain failed to detect reduction of metabolism in the somatosensory area or insular cortex. Exome analysis in the trio (patient and parents) failed to identify variants to be interpreted as a likely risk factor for EAC. CONCLUSION: We conclude that the presence of well-known risk factors (maleness, obesity, gastroesophageal reflux, and Barrett's metaplasia) in a patient with very limited capability of expressing discomfort or referring clinical symptoms have been the main risk factors for developing EAC. At present, based on the available data, there is no evidence of any increased risk of developing cancer in CdC patients.

The iGreenGO Study: The Clinical Role of Indocyanine Green Imaging Fluorescence in Modifying the Surgeon's Conduct During the Surgical Treatment of Advanced Gastric Cancer-Study Protocol for an International Multicenter Prospective Study.

Background: The near-infrared/indocyanine green imaging fluorescence (NIR/ICG) technology is showing promising results in several fields of surgical oncology. The clinical value of NIR/ICG technology in the surgical treatment of advanced gastric cancer (AGC) is not clearly established. Methods: This is the protocol of the "iGreenGO" (indocyanine Green Gastric Observation) Study, a national prospective multicenter study. Western patients who undergo curative-intent gastrectomy with D2 lymphadenectomy for AGC constitute the study cohort. All the patients undergo preoperative upper gastrointestinal endoscopy for submucosal peritumoral ICG injection at the most 20 h before surgery. Intraoperative endoscopic injection before starting surgical dissection is also allowed. The primary endpoint is the "change in the surgical conduct" (CSC), i.e., the need to perform further dissection after intraoperative NIR/ICG technology activation at the end of D2 lymphadenectomy. Secondary endpoints include the pattern of abdominal fluorescence distribution according to tumor and patient characteristics, the preoperative clinical variables potentially associated with CSC, and the incidence of stage migration due to NIR/ICG application. Discussion: The iGreenGO Study is the first study to investigate the clinical role of NIR/ICG technology for the surgical treatment of AGC in a large cohort of Western patients. Results from the present study can further clarify the role of NIR/ICG technology in surgical lymphadenectomy for AGC.

Multidimensional evaluation of the learning curve for laparoscopic complete mesocolic excision for right colon cancer: a risk-adjusted cumulative summation analysis.

AIM: Despite the suggested potential benefit of complete mesocolic excision (CME) for right-sided colon cancer (RCC) for patient survival, concerns about its safety and feasibility have contributed to delayed acceptance of the procedure, especially when performed by a minimally invasive approach. Thus, the aim of this work was to evaluate the actual learning curve (LC) of laparoscopic CME for experienced colorectal surgeons. METHOD: Prospectively collected data for consecutive patients undergoing laparoscopic CME for RCC between October 2015 and January 2021 at our institution, operated on by experienced surgeons, were analysed. A multidimensional assessment of the LC was performed through cumulative sum (CUSUM) and risk-adjusted (RA) CUSUM analysis. RESULTS: Two hundred and two patients operated by on by three surgeons were considered. The CUSUM graphs based on operating time showed one peak of the curve between 17 and 27 cases. The CUSUM graphs based on surgical failure showed one peak of the curve between 20 and 24 cases The RA-CUSUM curve also showed one preeminent peak at 24-33 cases. Based on the CUSUM and RA-CUSUM analyses all the surgeons reached proficiency in 24-33 cases. CONCLUSIONS: Our study showed that an experienced minimally invasive colorectal surgeon acquires proficiency in laparoscopic CME for RCC after performing 24-33 cases.

Laparoscopic gastrectomy for stage II and III advanced gastric cancer: long­term follow­up data from a Western multicenter retrospective study.

INTRODUCTION: There has been an increasing interest for the laparoscopic treatment of early gastric cancer, especially among Eastern surgeons. However, the oncological effectiveness of Laparoscopic Gastrectomy (LG) for Advanced Gastric Cancer (AGC) remains a subject of debate, especially in Western countries where limited reports have been published. The aim of this paper is to retrospectively analyze short- and long-term results of LG for AGC in a real-life Western practice. MATERIALS AND METHODS: All consecutive cases of LG with D2 lymphadenectomy for AGC performed from January 2005 to December 2019 at seven different surgical departments were analyzed retrospectively. The primary outcome was diseases-free survival (DFS). Secondary outcomes were overall survival (OS), number of retrieved lymph nodes, postoperative morbidity and conversion rate. RESULTS: A total of 366 patients with stage II and III AGC underwent either total or subtotal LG. The mean number of harvested lymph nodes was 25 ± 14. The mean hospital stay was 13 ± 10 days and overall postoperative morbidity rate 27.32%, with severe complications (grade ≥ III) accounting for 9.29%. The median follow-up was 36 ± 16 months during which 90 deaths occurred, all due to disease progression. The DFS and OS probability was equal to 0.85 (95% CI 0.81-0.89) and 0.94 (95% CI 0.92-0.97) at 1 year, 0.62 (95% CI 0.55-0.69) and 0.63 (95% CI 0.56-0.71) at 5 years, respectively. CONCLUSION: Our study has led us to conclude that LG for AGC is feasible and safe in the general practice of Western institutions when performed by trained surgeons.

Impact of neoadjuvant therapy followed by laparoscopic radical gastrectomy with D2 lymph node dissection in Western population: A multi-institutional propensity score-matched study.

BACKGROUND AND OBJECTIVES: In the setting of a minimally invasive approach, we aimed to compare short and long-term postoperative outcomes of patients treated with neoadjuvant therapy (NAT) + surgery or upfront surgery in Western population. METHODS: All consecutive patients from six Italian and one Serbian center with locally advanced gastric cancer who had undergone laparoscopic gastrectomy with D2 lymph node dissection were selected between 2005 and 2019. After propensity score-matching, postoperative morbidity and oncologic outcomes were investigated. RESULTS: After matching, 97 patients were allocated in each cohort with a mean age of 69.4 and 70.5 years. The two groups showed no difference in operative details except for a higher conversion rate in the NAT group (p = 0.038). The overall postoperative complications rate significantly differed between NAT + surgery (38.1%) and US (21.6%) group (p = 0.019). NAT was found to be related to a higher risk of postoperative morbidity in patients older than 60 years old (p = 0.013) but not in patients younger (p = 0.620). Conversely, no difference in overall survival (p = 0.41) and disease-free-survival (p = 0.34) was found between groups. CONCLUSIONS: NAT appears to be related to a higher postoperative complication rate and equivalent oncological outcomes when compared with surgery alone. However, poor short-term outcomes are more evident in patients over 60 years old receiving NAT.

ERAS pathway for gastric cancer surgery: adherence, outcomes and prognostic factors for compliance in a Western centre.

Adherence to an ERAS program guarantees an evidence-based approach for patient care, but the compliance to ERAS in patients undergoing surgery for gastric cancer in Western countries has not been clearly investigated. Our Institution has implemented an ERAS pathway (EP) for gastric surgery, composed of 24 items, since December 2016. We retrospectively analyzed the data of all consecutive patients undergoing surgery with curative intent for gastric cancer between January 2017 and December 2019 at our Institution, and were eligible for our EP. The primary endpoint was patients' compliance to the EP. Secondary endpoints were patients' adherence to each ERAS item and detection of variables associated with compliance failure. Seventy-three patients were included. Among these, 75.3% completed the EP, with a median number of items accomplished per patient of 21. Items with critical adherence were restrictive intraoperative fluid infusion (37%), avoidance of abdominal drain (14%), first clear liquid intake (67%), first solid food intake (48%). At univariate analysis age > 75 years, ASA > 2 and total gastrectomy were associated with failure to complete the EP. At multivariate analysis, ASA Score > 2 was the only preoperative factor associated with EP failure. Application of an ERAS program for malignant gastric surgery seems to be feasible with an acceptable completion rate in a tertiary referral Western centre. Preoperative factors, such as old age, advanced stage at diagnosis and neoadjuvant chemotherapy should not be considered as exclusion criteria for ERAS.

Prognostic value of pathological tumor regression grade in locally advanced gastric cancer: New perspectives from a single-center experience.

BACKGROUND AND OBJECTIVE: Perioperative chemotherapy (PC) with radical surgery represents the gold standard of treatment for resectable advanced gastric cancer (GC). The prognostic value of pathological tumor regression grade (TRG) induced by neoadjuvant chemotherapy (NACT) is not clearly established. This study aimed to investigate the correlation between TRG and survival in GC. METHODS: Patients affected by advanced GC undergoing PC and radical surgery were considered. TRG was assessed for each patient according to Becker's grading system. The correlation between TRG and survival was investigated. RESULTS: One-hundred patients were selected; 25 showed a good response (GR) (TRG 1a/1b), while 75 had a poor response (PR) (TRG 2/3) to NACT. GR patients showed better disease-free survival (DFS) (52 vs. 19 months, p < .001) and disease-specific survival (DSS) (57 vs. 25 months, p < .0001) when compared to PR patients. On univariate analysis, TRG, lymph node ratio (LNR), tumor size, grading, and post-neoadjuvant therapy TNM stage were significantly correlated with survival. On multivariate analysis, TRG, LNR and tumor size were independent prognostic factors for DFS and DSS. CONCLUSIONS: TRG, LNR, and tumor size are independent prognostic factors for DFS and DSS in patients with advanced GC undergoing NACT.

Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot.

Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P = 0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics.

Interleukin-32 Contributes to Human Nonalcoholic Fatty Liver Disease and Insulin Resistance.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder due to increased accumulation of fat in the liver and in many cases to enhanced inflammation. Although the contribution of inflammation in the pathogenesis of NAFLD is well established, the cytokines that are involved and how they influence liver transformation are still poorly characterized. In addition, with other modifiers, inflammation influences NAFLD progression to liver cirrhosis and hepatocellular carcinoma, demonstrating the need to find new molecular targets with potential future therapeutic applications. We investigated gene signatures in 38 liver biopsies from patients with NAFLD and obesity who had received bariatric surgery and compared these to 10 control patients who had received a cholecystectomy, using DNA microarray technology. A subset of differentially expressed genes was then validated on a larger cohort of 103 patients who had received bariatric surgery for obesity; data were thoroughly analyzed in terms of correlations with NAFLD pathophysiological parameters. Finally, the impact of a specific cytokine, interleukin-32 (IL32), was addressed on primary human hepatocytes (PHHs). Transcript analysis revealed an up-regulation of proinflammatory cytokines IL32, chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10 and of ubiquitin D (UBD), whereas down-regulation of insulin-like growth factor-binding protein 2 (IGFBP2) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) was reported in patients with NAFLD. Moreover, IL32, which is the major deregulated gene, correlated with body mass index (BMI), waist circumference, NAFLD activity score (NAS), aminotransferases (alanine aminotransferase [ALAT] and aspartate aminotransferase [ASAT]), and homeostasis model assessment of insulin resistance (HOMA-IR) index in patients. Consistent with an instrumental role in the pathophysiology of NAFLD, treatment of control human hepatocytes with recombinant IL32 leads to insulin resistance, a hallmark metabolic deregulation in NAFLD hepatocytes. Conclusion: IL32 has a critical role in the pathogenesis of NAFLD and could be considered as a therapeutic target in patients.

Laparoscopic gastrectomies for cancer: The ACOI-IHTSC national guidelines.

Guidelines for laparoscopy and cancer of stomach have been outlined by several scientific societies: The main recommendation being that laparoscopy should be used only by surgeons already highly skilled in gastric surgery. The laparoscopic approach to gastric cancer surgery has become more and more frequent in most Italian centers. On behalf of the Guideline Committee of the Italian Society of Hospital Surgeons and the Italian Hi-Tech Surgical Club, a panel of experts analyzed the highest evidence of all scientific papers focusing on laparoscopic gastrectomies for cancer and published from 2003 to 2011, and drew these national guidelines. Laparoscopic gastrectomy may be considered as a safe procedure with better short-term and comparable long-term results. compared to open gastrectomy (Grade A). There is a general agreement that a laparoscopic approach to the treatment of gastric cancer should be chosen only by surgeons already highly skilled in gastric surgery and other advanced laparoscopic interventions. Furthermore, the first procedures should be carried out during a tutoring program. Diagnostic laparoscopy is strongly recommended as the first step of laparoscopic as well as laparotomic gastrectomies (Grade B). Additional randomized controlled trials (RCT) that compare and investigate the long-term oncological outcomes of laparoscopic assisted gastrectomy are required.

Laparoscopic and mini-invasive surgery.

BACKGROUND: JGCA Gastric Cancer Treatment Guidelines (2004) include Laparoscopic Assisted Distal Gastrectomy (LADG) within the chapter of modified surgery. A metanalysis published in 2010 shows that LADG is significantly superior to Open Distal Gastrectomy (ODG) if comparing short term outcomes. Oncologic results prove to be comparable to ODG by one RCT and 2 retrospective studies. Little evidence is available on Laparoscopic Total Gastrectomy and concerns are raised about long-term oncologic outcomes. MATERIALS AND METHODS: Laparoscopic Subtotal Gastrectomy is carried out with 4 to 5 ports in the periumbilical region (Hasson trocar for laparoscope) and upper quadrants. After exploration of the abdominal cavity surgical steps include coloepiploic detachment, omentectomy, dissection of the gastrocolic ligament, division of the left gastroepiploic vessels, division of right gastroepiploic vessels, division of pyloric vessels. The duodenum is transected with a linear stapler. Incision of the lesser omentum and dissection of the hepatoduodenal ligament allows completion of D2 lymphadenectomy. The 4/5ths of the stomach are transected starting from the greater curve at the junction of left and right gastroepiploic arcades by linear stapler. Roux-en-Y loop reconstruction is performed through a stapled side-to-side gastro-jejunal anastomosis and a side-to-side jejuno-jejunal anastomosis. Reconstruction after Laparoscopic Total Gastrectomy is performed preferably by a side-to-side esophago-jejunal anastomosis according to Orringer. DISCUSSION AND CONCLUSION: A robotic assisted approach adds precision on lymphadenectomy and reconstructive techniques.