Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

BACKGROUND: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. METHODS: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. RESULTS: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. CONCLUSION: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.

Does conversion during minimally invasive rectal surgery for cancer have an impact on short-term and oncologic outcomes? Results of a retrospective cohort study.

BACKGROUND: Although minimally invasive rectal surgery (MIRS) for cancer provides better recovery for similar oncologic outcomes over open approach, conversion is still required in 10% and its impact on short-term and long-term outcomes remains unclear. The aim of our study was to evaluate the impact of conversion on postoperative and oncologic outcomes in patients undergoing MIRS for cancer. METHODS: From June 2011 to March 2020, we reviewed 257 minimally invasive rectal resections for cancer recorded in a prospectively maintained database, with 192 robotic and 65 laparoscopic approaches. Patients who required conversion to open (Conversion group) were compared to those who did not have conversion (No conversion group) in terms of short-term, histologic, and oncologic outcomes. Univariate and multivariate analyses of the risk factors for postoperative morbidity were performed. RESULTS: Eighteen patients (7%) required conversion. The conversion rate was significantly higher in the laparoscopic approach than in the robotic approach (16.9% vs 3.6%, p < 0.01). Among the 4 reactive conversions, 3 (75%) were required during robotic resections. Patients in the Conversion group had a higher morbidity rate (83.3% vs 43.1%, p = 0.01) and more severe complications (38.9%, vs 18.8%, p = 0.041). Male sex [HR = 2.46, 95%CI (1.41-4.26)], total mesorectal excision [HR = 2.89, 95%CI (1.57-5.320)], and conversion (HR = 4.87, 95%CI [1.34-17.73]) were independently associated with a higher risk of overall 30-day morbidity. R1 resections were more frequent in the Conversion group (22.2% vs 5.4%, p = 0.023) without differences in the overall (82.7 ± 7.0 months vs 79.4 ± 3.3 months, p = 0.448) and disease-free survivals (49.0 ± 8.6 months vs 70.2 ± 4.1 months, p = 0.362). CONCLUSION: Conversion to laparotomy during MIRS for cancer was associated with poorer postoperative results without impairing oncologic outcomes. The high frequency of reactive conversion due to intraoperative complications in robotic resections confirmed that MIRS for cancer is a technically challenging procedure.

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review.

BACKGROUND: Chyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy. METHODS: A systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality. RESULTS: Literature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases. CONCLUSIONS: The extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.

Safeness of Simultaneous Colonic Resection and Hepatic Radiofrequency Ablation.

Background and Objectives: Previous reports showed an increased risk of infectious complications when liver radiofrequency ablation (RFA) is performed simultaneously to colorectal resection. The aim of this study was to compare early and long-term outcomes of simultaneous versus staged strategy. Methods: Data from colorectal cancer liver metastases consecutively treated by surgery of the primary tumor with an associated liver RFA procedure between January 1, 2010 and January 31, 2020. Patients were divided into two groups: RFA performed during colorectal surgery (simultaneous) or in a different moment (staged). Patients were manually matched (1:1) to minimize influence of known covariates. Results: Seventy-two patients were included. After matching, there was no difference between the two groups in morbidity or mortality. Hospital stay was 2 days shorter in the simultaneous group. Conclusions: Early or long-term outcomes were identical between the two strategies. The simultaneous strategy was associated with a shorter duration of hospitalization although not significant. Simultaneous colorectal resection and liver RFA is safe and must be included in surgeons' armamentarium.

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights.

Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. However, IPMNs and IPMCs include distinct subtypes of precursor (gastric, pancreato-biliary, intestinal) and invasive (tubular, colloid) lesions, also associated to specific characteristics. Notably, consistent data have shown intestinal IPMNs and associated colloid carcinomas, defining the "intestinal pathway", to be associated with less aggressive features. Genomic specificities have also been uncovered, such as mutations of the GNAS gene, and recent data provide more insights into the mechanisms involved in IPMCs carcinogenesis. This review synthetizes available data on clinical-pathological features and outcomes associated with IPMCs and their subtypes. We also describe known genomic hallmarks of these lesions and summarize the latest data about molecular processes involved in IPMNs initiation and progression to IPMCs. Finally, potential implications for clinical practice and future research strategies are discussed.

Transitioning From Open to Robotic Liver Resection. Results of 46 Consecutive Procedures Including a Majority of Major Hepatectomies.

Aims. Minimally invasive liver resection is a complex and challenging operation. Although authors have reported robotic liver resection shows improved safety and efficacy compared with open liver resection, robotic major liver resections for malignant liver lesions treatment remain inadequately evaluated. The aims of the present study were to evaluate the feasibility and safety of transitioning from open to robotic liver resection in a nonuniversity hospital. Patients and Methods. From December 2015 to March 2020, 46 patients underwent totally robotic-assisted liver resections out of 446 robotic procedures. Also, we retrospectively reviewed the last 27 open right hepatectomies (ORHs) and compared then with the first 25 anatomic robotic-assisted right hepatectomies (RRHs). Results. Mean operative time, mean blood lost, rate of complications, and mean hospital stay were associated with the complexity of the procedure. The comparison between ORH and RRH showed that intraoperative complications were less frequently observed during ORH whereas RRH showed a trend in favor of less blood loss. ORH had a trend toward smaller surgical margins and higher rate of R1 resections. Recurrence occurred in 31 (59%) patients and was more frequently observed after ORH. However, the mean follow-up was significantly shorter after RRH. Conclusion. Our study demonstrated the technical feasibility and safety of transitioning from open to robotic liver resection (including major hepatectomies) in a nonuniversity setting. Higher costs remain an important drawback for robotic surgery.

Teaching robotic rectal cancer surgery at your workplace: does the presence of visiting surgeons in the operating room have a detrimental effect on outcomes?

BACKGROUND: Surgery demonstration (SD) is considered to be a mainstay of surgical education, but controversy exists concerning the patient's safety. Indeed, the presence of visiting surgeons is a source of distraction and may have an impact on surgeon's performance. This study's objective was to evaluate possible differences in outcomes between robotic sphincter-saving rectal cancer surgery (RRCS) performed during routine surgical practice versus in the presence of visiting surgeons in the operating room (OR) with direct access to the surgeon. METHODS: Retrospective case-matched studies were conducted from a prospectively collected database. 114 patients (38 with the presence of visiting surgeons) who underwent RRCS between January 2013 and September 2018 were included. Patients were matched in a 1:2 basis after propensity score analysis using five criteria: gender, body mass index, preoperative chemoradiation, type of mesorectum excision, and synchronous liver metastasis. RESULTS: There was no difference between the two groups with regard to mean operating time, estimated blood loss, conversion, and hospital stay. Also, overall (44% vs. 40%; P = 0.6), major morbidity (26% vs. 19%; P = 0.5), and unplanned reoperation (17% vs. 15%; P = 1.0) rates were not statistically different. No difference was noted with regard to the quality of mesorectum excision, or positive rate of circumferential and distal longitudinal resection margins. The mean number of harvested lymph nodes (17 vs. 14.5; P = 0.04) was lower in the SD group and the number of patients with < 12 harvested lymph nodes (31% vs. 16%; P = 0.09) was greater after SD although it did not reach statistical significance. No differences were observed in disease-free or overall survival. CONCLUSIONS: The presence of visiting surgeons in the OR seems not to interfere in the quality of rectal resection and does not compromise patient's short-term outcome and survival. However, mild differences in the extent of lymphadenectomy were observed and the surgeons performing SD may be aware of this.

Pancreatic ductal adenocarcinoma harboring microsatellite instability / DNA mismatch repair deficiency. Towards personalized medicine.

Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained almost unchanged for many decades. Pancreatic cancer has few prevalent genetic mutations. Available data on dMMR pancreatic cancer is limited and heterogeneous with regard to its prevalence and prognostic implications. Discordant results are mainly due to differences in detection methods and sample sizes. Interest in dMMR is growing since initial reports on immune checkpoint inhibition therapy for pancreatic cancer has shown it to be effective, generating impressive and durable responses. However, it has been accompanied by several questions regarding the appropriate screening, detection tools, patient selection, timing and modality of testing. Herein, we provide an extensive literature review and outline recommendations for testing.

Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases.

BACKGROUND: Histomorphological features have been described as prognostic factors after resection of colorectal liver metastases (CLM). The objectives of this study were to assess the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDC) among CLM, and their association with other prognostic factors. METHODS: We evaluated 229 patients who underwent a first resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory infiltrate. Lymphatic and portal invasion were evaluated through D2-40 and CD34 antibody. RESULTS: Factors independently associated with poor overall survival were nodules>4 (P = 0.002), presence of PDC G3 (P = 0.007), portal invasion (P = 0.005), and absence of tumor pseudocapsule (P = 0.006). Factors independently associated with disease-free survival included number of nodules>4 (P < 0.001), presence of PDC G3 (P = 0.005), infiltrative border (P = 0.031), portal invasion (P = 0.006), and absent/mild peritumoral inflammatory infiltrate (P = 0.002). PDC and TB were also associated with histological factors, as portal invasion (TB), peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of tumor pseudocapsule (TB and PDC). CONCLUSIONS: This is the first study demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor, but it was not an independent predictor of survival.

Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

Robotic versus laparoscopic rectal resection for sphincter-saving surgery: pathological and short-term outcomes in a single-center analysis of 130 consecutive patients.

BACKGROUND: Minimally invasive sphincter-saving rectal resection represents a challenging procedure. Robotic surgery for rectal cancer has several advantages over conventional surgery in performing precise dissection and was proved to be safe and effective in previous studies. However, comparison between laparoscopic and robotic rectal resection has drawn contradictory results. The aim of the present study was to compare robotic and laparoscopic sphincter-saving rectal resections for short-term and pathological outcomes. METHODS: Between January 2013 and May 2016, we performed a total of 258 robotic surgeries, including 146 colorectal resections (56%). For this study, we included the first 65 sphincter-saving robotic resections and compared them to the last 65 consecutive laparoscopic resections. The laparoscopic group was constituted by the last 65 consecutively operated patients who matched the inclusion criteria. RESULTS: Patients' baseline characteristics were similar in both the groups. Conversion rate was greater in the laparoscopic group (17 vs. 5%, p=0.044). Reoperation rate, overall and severe morbidity, and median hospital stay were similar in both the groups. Quality of mesorectal excision specimen was considered complete or near complete in 97 and 96% in the laparoscopic and robotic groups, respectively. There was no difference in the rates of negative circumferential radial margin, distal margin, and surgical success measured by composite criteria. CONCLUSION: The main finding of this study was that robotic proctectomy for sphincter-saving procedures offers similar quality of TME with a statistically significant lower rate of conversion when compared to laparoscopic proctectomy.

Combined stoma reversal and liver resection: a matched case-control study.

BACKGROUND: Stoma reversal can be performed during liver resection (LR) in patients with colorectal liver metastases (CRCLM) whose primary colorectal tumor has been previously resected with a diverting loop ileostomy. This combined procedure is reputed to be associated with an increased morbidity. This study investigates the impact of simultaneous loop ileostomy closure (LIC) on the postoperative outcome of LR for CRCLM. METHODS: From November 1996 to April 2012, 408 patients who underwent LR for CRCLM were retrospectively studied from a prospective database. Patients who underwent simultaneous LR and LIC were matched for the type of the main liver procedure, the use of preoperative chemotherapy and the need for greater than or equal to 6 cycles of preoperative chemotherapy with LR only patients. Intraoperative and postoperative complications were recorded and compared. RESULTS: Twenty-four patients (6%) with simultaneous LR and LIC were matched with 72 patients with LR only. Both groups were comparable for patients' demographics and intraoperative findings. Liver related (P = .957) and overall postoperative morbidity (P = .643) rates did not differ between groups. CONCLUSION: The combined procedure appeared to be safe when strict surgical technique is used.

Stump appendicitis. A diagnostic trap.

Stump appendicitis is an underestimated condition and a diagnostic trap that few surgeons think about when faced against localized pain in the lower-right abdomen. Misdiagnosis and therefore delay of the appropriate treatment results in increased morbidity. We report the case of a patient who presented a 7-day history of right iliac fossa abdominal pain. She had undergone open appendectomy in childhood. Stump appendicitis was not diagnosed immediately despite imaging (CT and MRI) and exploratory laparoscopy. In conclusion, surgeons and gastroenterologists need a heightened awareness of the possibility of stump appendicitis.

Tumor growth pattern as predictor of colorectal liver metastasis recurrence.

BACKGROUND: Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence. METHODS: We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing). RESULTS: Tumor recurrence was observed in 65 patients (71.4%). According to multivariate analysis, 3 or more lesions (P = .05) and the infiltrative tumor margin type (P = .05) were unique independent risk factors for recurrence. Patients with infiltrative margins had a 5-year disease-free survival rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P = .05). CONCLUSIONS: CRM patients with pushing margins presented superior disease-free survival rates compared with patients with infiltrative margins. Thus, the adoption of the margin pattern can represent a tool for improved selection of patients for adjuvant treatment.

Dimensão da margem cirúrgica nas ressecções de metástase hepática de câncer colorretal: impacto na recidiva e sobrevida / Surgical margin size in hepatic resections for colorectal metastasis: impact on recurrence and survival

RACIONAL: Aproximadamente 50% dos pacientes com tumor colorretal apresentam metástase hepática sendo a hepatectomia o procedimento terapêutico de escolha. Discutem-se diversos fatores prognósticos; entre eles, a margem cirúrgica é fator sempre recorrente, pois não existe consenso da distância mínima necessária entre o nódulo metastático e a linha de secção hepática. OBJETIVOS: Avaliar as margens cirúrgicas nas ressecções de metástases hepáticas de câncer colorretal e sua correlação com recidiva local e sobrevida. MÉTODOS: Estudo retrospectivo, baseado na revisão dos prontuários de 91 pacientes submetidos à ressecção de metástases hepáticas de neoplasia colorretal. Foi realizada revisão histopatológica de todos os casos com aferição da menor margem cirúrgica e observar o resultado tardio em relação à recidiva e sobrevida. RESULTADOS: Não houve diferença estatística nas taxas de recidiva e no tempo de sobrevivência global entre os pacientes com margens livres ou acometidas (R0vsR1), assim como não houve diferença entre as margens subcentimétricas e as maiores de 1 cm. A sobrevida livre de doença dos pacientes com margens microscopicamente acometidas foi significativamente menor do que dos com margens livres. A análise uni e multivariada não identificou a margem cirúrgica (R1, exígua ou menor que 1 cm) como fator de risco para recidiva. CONCLUSÕES: As ressecções de metástases hepáticas com margens livres de doença, independentemente das dimensões da margem, não influenciou na recidiva tumoral (intra ou extra-hepática) ou na sobrevida dos pacientes.

BACKGROUND: Approximately 50% of the patients with a colorectal tumor develop liver metastasis, for which hepatectomy is the standard care. Several prognostic factors have been discussed, among which is the surgical margin. This is a recurring issue, since no consensus exists as to the minimum required distance between the metastatic nodule and the liver transection line. AIM: To evaluate the surgical margins in liver resections for colorectal metastases and their correlation with local recurrence and survival. METHODS: A retrospective study based on the review of the medical records of 91 patients who underwent resection of liver metastases of colorectal cancer. A histopathological review was performed of all the cases; the smallest surgical margin was verified, and the late outcome of recurrence and survival was evaluated. RESULTS: No statistical difference was found in recurrence rates and overall survival between the patients with negative or positive margins (R0 versus R1); likewise, there was no statistical difference between subcentimeter margins and those greater than 1 cm. The disease-free survival of the patients with microscopically positive margins was significantly worse than that of the patients with negative margins. The uni- and multivariate analyses did not establish the surgical margin (R1, narrow or less than 1 cm) as a risk factor for recurrence. CONCLUSION: The resections of liver metastases with negative margins, independently of the margin width, had no impact on tumor recurrence (intra- or extrahepatic) or patient survival.