Jacopo Weindelmayer

Western strategy for EGJ carcinoma

In this paper, the epidemiological and clinicobiological behavior of esophagogastric junction (EGJ) adenocarcinoma in the West is compared and contrasted to that in the East, and an overview is provided of current therapeutic strategies employed for this type of tumor in Western countries. It is well known that multimodal treatment is the therapeutic standard in locally advanced EGJ adenocarcinoma, but whether neoadjuvant/perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) is the optimal approach is still debated. Neoadjuvant CRT improves local control in locally advanced Siewert type I and II tumors, so it should be considered the treatment of choice. In the subset of these patients with microscopic systemic disease at diagnosis, more intensive exclusive chemotherapy protocols could be of benefit. Therefore, there is an urgent need to identify these patients before planning the treatment. For Siewert type III tumors, perioperative chemotherapy is the standard. While there is general agreement on the optimal surgical approach for Siewert types I and III (a two-field Ivor Lewis operation and a total gastrectomy with distal esophagectomy, respectively), no standard surgical treatment has been defined for Siewert type II tumors. When data from Western series on proximal and circumferential resection margins and on nodal spread in Siewert type II tumors are taken into account, the optimal surgical approach appears to be Ivor Lewis esophagectomy. Whether the extent of esophageal invasion can correctly predict nodal involvement in middle–upper mediastinal stations as a means to restrict indications for transthoracic esophagectomy requires further investigation in the West.

ypN0: Does It Matter How You Get There? Nodal Downstaging in Esophageal Cancer

BackgroundypN0 following induction treatment for advanced esophageal cancer improves survival. Importance of how ypN0 is achieved is unknown. This study evaluates survival in “natural” N0 (cN0/ypN0) and “downstaged” N0 (cN+/ypN0) patients.MethodsAmong patients treated with induction treatment and surgery, 83 CT scans were retrieved in digital format and re-evaluated by a radiologist, blinded to pathological nodal status: 28 natural N0, 37 downstaged N0, and 18 ypN+. Impact of N0 classification on survival and associations with survival were identified.ResultsSurvival varied with ypN: 3-year survival was 84 % for natural N0 patients, 59 % for downstaged N0, and 20 % for ypN+ (p < .001). Compared with natural N0 patients, risk of cancer mortality was 3.8 for downstaged N0 and 7.6 for ypN+ (p = .01). Survival was also stratified by ypT: compared with ypT0 natural N0, who had the best survival, intermediate survival was seen in ypT+ natural N0 [hazard ratio (HR), 1.3] and ypT0 downstaged N0 (HR, 1.8), and poor survival in ypT+ downstaged N0 (HR, 9.5) and ypN+ (HR, 12.0) (p = .026).ConclusionsNatural N0 and downstaged N0 patients are different clinical entities: downstaging cN+ with induction treatment producing downstaged N0 improves survival only if there is concomitant primary cancer downstaging to ypT0. Intermediate survival is seen in downstaged N0 patients with complete tumor response. Natural N0 patients experience intermediate survival with incomplete response (ypT+). Complete response in natural N0 patients produces the best survival. Means of obtaining ypN0 status matters and requires a complete response for downstaged N0 patients to benefit from induction treatment.

Genetic prediction of long-term survival after neoadjuvant chemoradiation in locally advanced esophageal cancer

Candidate genes involved in DNA repair, 5-fluorouracil metabolism and drug detoxification were genotyped in 124 patients receiving neoadjuvant chemoradiation treatment for locally advanced esophageal cancer and their predictive role for long-term relapse-free survival (RFS) and cancer-specific survival (CSS) were evaluated. A panel including MTHFR 677TT, MDR1 2677GT, GSTP1 114CC, XPC 499CC and XPC 939AC+CC, defined as high-risk genotypes, discriminated subgroups with significantly different outcomes. When the panel was combined with histology, patients split into two subsets with 5-year RFS and CSS rates of 65% vs 27% (hazard ratio (HR) 3.0, P<0.0001) and 69% vs 31% (HR 2.9, P<0.0001), respectively. Combining the 5-single-nucleotide polymorphism (5-SNP) panel with pathological response defined two major informative risk classes with 5-year PFS and CSS rates of 79.4% vs 17.7% (HR 6.71, P<0.0001) and 79.3% vs 26.3% (HR 6.25, P<0.0001), respectively. This classification achieved a sensitivity of 79%, a specificity of 85.4% and an accuracy of 81.8%.

Enhanced recovery after surgery protocol in patients undergoing esophagectomy for cancer: a single center experience

This article is about an emerging issue in esophageal surgery: enhanced recovery after surgery (ERAS) Few data are published in literature and its safety and feasibility is still debated. The focus of our paper is on the feasibility of an ERAS protocol for esophagectomy (including both the Ivor-Lewis and McKeown procedure) in a high volume center comparing to a standard perioperative protocol. We introduced a novelty item on this type of surgery: resume of oral feeding in the first postoperative day. We analyzed the dropout rate for each item and the postoperative morbidity. We studied 39 patients operated in the Upper GI division of Verona University Hospital between January 2013 and August 2014; 22 patients (ERAS group) were studied in a perspective way while 17 patients (standard group) were studied retrospectively. The enhanced recovery protocol included intraoperative fluid management, time of extubation after surgery, intensive care unit discharge, drains and nasogastric tube management, mobilization of the patient, oral food intake. We compared the results between the two groups in term of hospital stay, postoperative morbidity and mortality. We also calculated the percentage completion of the protocol, evaluating patient drop-out rates for each of the items. Patients showed an improvement in the ERAS group in terms of earlier extubation, earlier intensive care unit discharge (p < 0.01), earlier thoracic drain, urinary catheter (p < 0.01) and nasogastric tube removal (p = 0.02), earlier mobilization (p < 0.01), and resume of oral feeding (p < 0.01). Median length of hospital stays in the ERAS group was 9 days while in the standard group was 10 days (p = 0.23). Postoperative morbidity and mortality were comparable between the two groups. This study shows the feasibility and safety of an ERAS protocol for esophageal surgery in a high-volume center. These data strengthen the literature results on this argument calling for larger sample size studies.

Para-aortic lymphadenectomy in surgery for gastric cancer: current indications and future perspectives

Involvement of para-aortic nodes (PAN) has been detected at pathological examination in 10–25% of locally advanced gastric cancer. Based on these data of nodal diffusion, the lymphadenectomy of para-aortic stations would be desirable in locally advanced gastric cancer. However, the debate on the oncological benefit of para-aortic nodes dissection is still not solved. A review of the literature was performed and papers reporting either the rate of para-aortic nodal metastases or the long-term survival outcomes after D2+ para-aortic nodes dissection (PAND) or D3 lymphadenectomy were descriptively reported. The literature survey yielded 14 studies. Most of the papers show the outcome of series of advanced gastric cancer treated with surgery alone, while starting from 2012, 3 articles report the outcomes of D2 + PAND or D3 lymphadenectomy after preoperative chemotherapy. The rate of PAN metastases ranges between 8.5 and 28% in surgical series. Survival outcomes largely improved in series of patients treated with multimodal approach compared to those of surgery alone. In patients with clinically detected para-aortic nodal metastases, preoperative chemotherapy followed by PAND is indicated. More data are needed to clarify the indication to prophylactic PAND in the era of multimodal treatment, anyway super-extended lymphadenectomies have to be performed by experienced surgeons in dedicated centres.

Acute bleeding obstruction pancreatitis after Roux-en-Y anastomosis in total gastrectomy: a single center experience

Anastomotic intraluminal bleeding is a well-known complication after total gastrectomy. Nevertheless, few data are published on acute bleeding obstruction pancreatitis (BOP) due to a bleeding from the jejunojejunostomy (JJ). In this paper we describe our experience. A total of 140 gastrectomies for EGJ cancer were performed in our Institute from January 2012 to January 2017. All reconstructions were performed with a Roux-en-Y anastomosis: a mechanical end-to-side esophago-jejunostomy and a mechanical end-to-side JJ. Three patients suffered from a bleeding at the JJ with a consequent BOP. We analyzed the time of diagnosis, the treatment and the outcomes. The three patients presented anemia at the laboratory findings on postoperative day (POD) 1. In patient I laboratory findings of acute pancreatitis were found in POD 2. CT scan was performed and showed signs of BOP. Endoscopic treatment was tried without success. Therefore, patient underwent surgery: JJ take down, bleeding control and anastomosis rebuild were performed. In spite of this the patient died of MOF in POD 4. Patient II had a persistent anemia treated with blood transfusions until POD 3, when laboratory tests showed increased lipase and bilirubin levels. Patient was successfully treated with endoscopy but several blood transfusions and a prolonged recovery were necessary. Patient III had laboratory findings of acute pancreatitis on POD 1. Immediate surgery was performed and patient was discharged on POD 9 without sequelae. BOP is a rare but deadly complication after Roux-en-Y anastomosis. An early diagnosis and an aggressive treatment seem to improve the outcome.

Do all the European surgeons perform the same D2? The need of D2 audit in Europe

Although D2 lymphadenectomy is the standard of care for radical intent surgical treatment of gastric cancer, the real compliance with D2 dissection in Europe is still unknown. The aim of the present study is to analyze the variation in lymph-node harvesting reported after D2 dissection in European series and to present a European project aiming at evaluating the real compliance with D2 lymphadenectomy. A PubMed search for papers using the key words “D2 lymphadenectomy” and “gastric cancer” from 2008 to 2017 was undertaken. Only studies by European authors in English language reporting the number of retrieved lymph nodes after D2 lymphadenectomy were included. The results of literature review were descriptively reported. The literature survey yielded 16 studies: 2 RCTs, 3 observational multicentre studies, and 11 observational monocentric studies. A large variability was found in the number of retrieved nodes, which, overall, was the lowest in the surgical series from Eastern Europe (16.6 and 19.9 in the Lithuanian and Hungarian series, respectively) and the highest in an Italian RCT. The within-study variability was also quite high, especially in multicentre RCTs and observational studies. Sample size tended to have a larger effect on the variability of lymph nodes retrieved than on its actual value. However, in both cases, the relation was not significant, due to the low number of studies considered. There is a large variability in the number of retrieved nodes after D2 dissection in European series. This reflects, at least partly, different approaches to D2 lymphadenectomy by European surgeons and may be responsible of the different outcomes observed in patients with gastric cancer across Europe. Therefore, there is the need to standardize the practice of D2 gastrectomy in Europe and to define possible variations of D2 procedures according to tumour’s characteristics.

Lymphadenectomy: how to do it?

According to the more recent European guidelines, the D2 lymphadenectomy is considered the standard for curative intent treatment of patients with gastric cancer. Although, the surgical definition of D2 dissection and its technical aspects had been learned from Eastern surgeons in the past decades, some variations in the approach to D2 lymphadenectomy by European surgeons were detectable in randomized clinical trials dealing with lymphadenectomy. Despite in more recent years an improvement in surgical quality has been reported in European series, some differences in the practice of D2 dissection are thought to persist. As, these may contribute to discrepancies in gastric cancer survival observed across European countries, the standardization of surgical quality is an urgent need to improve the outcome of gastric cancer patients in Europe. In this manuscript, we focus on the technical aspects of the D2 dissection both in open and laparoscopic gastrectomy in order to contribute to the improvement of surgical care of gastric cancer in the West.

Long-Term Results with Surgery Alone and Multimodal Treatments

Esophagogastric junction (EGJ) adenocarcinoma survival improved recently, thanks to the use of multimodal treatments. Survival with surgery alone is instead still poor in all locally advanced and node-positive patients. Recurrence is still the main cause of death, and it is particularly high within 24 months. In this chapter we will discuss the long-term results with surgery alone and multimodal treatments in EGJ cancer patients and then the characteristics and types of recurrence.

Morbid-Mortality and Treatment of Complications

Despite the growing importance of chemotherapy and radiotherapy, surgery is still the preferred curative treatment for esophageal adenocarcinoma. Depending on the esophageal and gastric involvement of this tumor, a gastrectomy or an esophagectomy is required. The latter needs an abdomino-thoracic approach or a gastric pull-up, resulting in an increased morbidity and mortality.