Needs, preferences, and patient participation for a randomized controlled trial on postneoadjuvant complete tumor response: A qualitative study of patients with esophageal cancer.

PURPOSE: For patients with clinical complete response of non-metastatic esophageal cancer (EC) after neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT), the two treatment options obligate postneoadjuvant surgery as the current standard treatment (surgery on principle) versus active surveillance with surgery as needed only in recurring loco-regional tumor as a possible future alternative or standard exist. Since these treatments are presumably equivalent in terms of overall survival, patient-centered information can encourage the discussion with the treating physician and can make it easier for patients to make trade-offs between the advantages and disadvantages of the treatment alternatives in a highly distressed situation. METHODS: A qualitative prospective cross-sectional study was conducted to create patient-centered information material that is based on patients' preferences, needs, and concerns regarding the two treatment options, and to investigate the potential participation in a consecutive randomized controlled trial (RCT). Therefore, EC patients (N = 11) were asked about their attitudes. RESULTS: Concerns about the surgery and possible postoperative impairments in quality of life were identified as most mentioned negative aspects of surgery on principle, and recurrence and progression fear and the concern that surgery cannot be avoided anyways as most named negative aspects of surgery as needed. In regard to the participation in an RCT, making a contribution to science and the hope that the novel therapy would be superior to the established one were relevant arguments to participate. On the other hand, the lack of a proactive selection of treatment was named an important barrier to participation in an RCT. CONCLUSION: The importance of adapting medical conversations to the patients' lack of expertise and their exceptional cognitive and emotional situation is stressed. Results of this study can be used to improve patient-centered information and the recruitment of patients in RCTs in cancer.

[Technique of Colon Interposition for Oesophageal Replacement for Oesophageal Cancer]. / Technik der Koloninterposition zum Ösophagusersatz beim Ösophaguskarzinom.

Nowadays, it is only relatively rare and in selected situations that colonic interposition is chosen rather than the stomach as a reconstructive organ for replacing the oesophagus. The colon is a reliable organ for tubular replacement of the oesophagus when the stomach is not available for reconstruction. Colon interposition is a complex and complicated operation. It requires a specific indication and thorough preoperative preparation. From a technical point of view, colon interposition places high demands on the selection and surgical dissection of the vascular supply to the reconstructed organ. The reconstruction route and elevation of the interposition graft to the proximal oesophagus and the need to create 3 or 4 gastrointestinal anastomoses also place significantly higher demands than reconstruction using a gastric tube. Overall, despite the significant surgery-related morbidity, good functional results and a good quality of life can usually be achieved. The surgical technique applied in our own practice is described in detail. An overview from literature on the results of colonic interposition is given, particularly with regard to surgical complications and quality of life after colon interposition.

[Technique of Colon Interposition for Oesophageal Replacement for Oesophageal Cancer]. / Technik der Koloninterposition zum Ösophagusersatz beim Ösophaguskarzinom.

Nowadays, it is only relatively rare and in selected situations that colonic interposition is chosen rather than the stomach as a reconstructive organ for replacing the oesophagus. The colon is a reliable organ for tubular replacement of the oesophagus when the stomach is not available for reconstruction. Colon interposition is a complex and complicated operation. It requires a specific indication and thorough preoperative preparation. From a technical point of view, colon interposition places high demands on the selection and surgical dissection of the vascular supply to the reconstructed organ. The reconstruction route and elevation of the interposition graft to the proximal oesophagus and the need to create 3 or 4 gastrointestinal anastomoses also place significantly higher demands than reconstruction using a gastric tube. Overall, despite the significant surgery-related morbidity, good functional results and a good quality of life can usually be achieved. The surgical technique applied in our own practice is described in detail. An overview from literature on the results of colonic interposition is given, particularly with regard to surgical complications and quality of life after colon interposition.

Multidisciplinary Application of Robotic Surgery in Cancer Disease.

Robotic assistance systems are utilized in minimally invasive surgery with a rapidly increasing frequency [...].

Postoperative Hiatal Hernia after Ivor Lewis Esophagectomy-A Growing Problem in the Age of Minimally Invasive Surgery.

BACKGROUND: Even though minimally invasive esophagectomy is a safe and oncologically effective procedure, several authors have reported an increased risk of postoperative hiatal hernia (PHH). This study evaluates the incidence and risk factors of PHH after hybrid minimally invasive (HMIE) versus open esophagectomy (OE). METHODS: A retrospective single-center analysis was performed on patients who underwent Ivor Lewis esophagectomy between January 2009 and April 2018. Computed tomography scans and patient files were reviewed to identify the PHH. RESULTS: 306 patients were included (152 HMIE; 154 OE). Of these, 23 patients (8%) developed PHH. Most patients (13/23, 57%) were asymptomatic at the time of diagnosis and only 4 patients (17%) presented in an emergency setting with incarceration. The rate of PHH was significantly higher after HMIE compared to OE (13.8% vs. 1.3%, p < 0.001). No other risk factors for the development of PHH were identified in uni- or multi-variate analysis. Surgical repair of PHH was performed in 19/23 patients (83%). The recurrence rate of PHH after surgical repair was 32% (6/19 patients). CONCLUSIONS: The development of PHH is a relevant complication after hybrid minimally invasive esophagectomy. Although most patients are asymptomatic, surgical repair is recommended to avoid incarceration with potentially fatal outcomes. Innovative techniques for the prevention and repair of PHH are urgently needed.

Oncological recurrence following pathological complete response after neoadjuvant treatment in patients with esophageal cancer - a retrospective cohort study.

BACKGROUND: To evaluate recurrence in patients with post-neoadjuvant pathological complete response (pCR) and in patients with complete response of primary tumor but persisting lymphatic spread of disease (non-pCR, ypT0ypN +) of esophageal cancer. METHODS: Seventy-five patients (63 pCR, 12 non-pCR) were analyzed retrospectively. Pattern and incidence of local and distant recurrence as well as the impact on overall (OS) and disease-free survival (DFS) were evaluated. The efficacy of neoadjuvant chemotherapy according to FLOT protocol was compared to neoadjuvant chemoradiation according to CROSS protocol. RESULTS: In the pCR group, isolated local recurrence was diagnosed in 3%, while no isolated local recurrence was observed in the non-pCR group due to the high incidence of distant recurrence. Distant recurrence was most common in both cohorts (isolated distant recurrence: pCR group 10% to non-pCR group 55%; simultaneous distant and local recurrence: pCR group 3% to non-pCR group 18%). Median time to distant recurrence was 5.5 months, and median time to local recurrence was 8.0 months. Cumulative incidence of distant recurrence (with and without simultaneous local recurrence) was 16% (± 6%) in pCR patients and 79% (± 13%) in non-pCR patients (hazard ratio (HR) 0.123) estimated by Kaplan-Meier method. OS (HR 0.231) and DFS (HR 0.226) were significantly improved in patients with pCR compared to patients with non-pCR. Advantages for FLOT protocol compared to CROSS protocol, especially with regard to distant control of disease (HR 0.278), were observed (OS (HR 0.361), DFS (HR 0.226)). CONCLUSION: Distant recurrence is the predominant site of treatment failure in patients with pCR and non-pCR grade 1a regression, whereby recurrence rates are much higher in patients with non-pCR.

Cancer-associated Macrophage-like Cells in Patients with Non-metastatic Adenocarcinoma of the Esophagus - Cytomorphological Heterogeneity.

Introduction: Esophageal adenocarcinoma (EAC) often recurs systemically despite therapy with a curative aim. New diagnostic and therapeutic approaches are urgently needed. A promising field is liquid biopsy, meaning the investigation of tumor-associated cells in the peripheral blood, for example cancer-associated macrophage-like cells (CAML). The aim of this multicentric study was to investigate the presence and cytomorphological appearance of CAML in patients with non-metastatic and operable esophageal cancer. Methods: Blood samples from 252 patients with locally advanced EAC were obtained before starting curative treatment including surgery, and then processed using ScreenCell® filtration devices. Cytological analysis was performed via May-Grünwald-Giemsa staining. CAML were defined by their morphological characteristics. We also performed immunofluorescence staining with the mesenchymal marker vimentin on a subset of our study cohort. Results: We detected cytomorphologically heterogeneous CAML in 31.8% (n=80) patients. Their presence and cell count did not correlate significantly with pretherapeutic cTNM. Even in patients with small tumors and no lymph-node infiltration, cell counts were high. CAML showed heterogenous staining patterns for vimentin. Conclusion: This is one of the first studies demonstrating the presence and phenotype of CAML in a uniquely broad cohort of EAC patients. As they are believed to be representatives of the inflammatory tumor microenvironment shed into the bloodstream, their presence in non-metastatic EAC is a promising finding.

Pathological complete response in multimodal treatment of esophageal cancer: a retrospective cohort study.

To evaluate pathological complete response (pCR, ypT0ypN0) after neoadjuvant treatment compared with non-complete response (non-CR) in patients with esophageal cancer (EC), and 393 patients were retrospectively analyzed. Survival probability was analyzed in patients with: (i) pCR vs non-CR; (ii) complete response of the primary tumor but persisting lymphatic metastases (non-CR-T0N+) and (iii) pCR and tumor-free lymphnodes exhibiting signs of postneoadjuvant regression vs. no signs of regression. (i) Median overall survival (mOS) was favorable in patients with pCR (pCR: mOS not reached vs. non-CR: 41 months, P < 0.001). Multivariate analysis revealed that grade of regression was not an independent predictor for prolonged survival. Instead, the achieved postneoadjuvant TNM-stage (T-stage: Hazard ratio [HR] ypT3-T4 vs. ypT0-T2: 1.837; N-stage: HR ypN1-N3 vs. ypN0: 2.046; Postneoadjuvant M-stage: HR ypM1 vs. ycM0: 2.709), the residual tumor (R)-classification (HR R1 vs. R0: 4.195) and the histologic subtype of EC (HR ESCC vs. EAC: 1.688) were prognostic factors. Patients with non-CR-T0N+ have a devastating prognosis, similar to those with local non-CR and lymphatic metastases (non-CR-T + N+) (non-CR-T0N+: 22.0 months, non-CR-T + N-: mOS not reached, non-CR-T + N+: 23.0 months; P-values: non-CR-T0N+ vs. non-CR-T + N-: 0.016; non-CR-T0N+ vs. non-CR-T + N+: 0.956; non-CR-T + N- vs. non-CR-T + N+: <0.001). Regressive changes in lymphnodes after neoadjuvant treatment did not influence survival-probability in patients with pCR (mOS not reached in each group; EAC-patients: P = 0.0919; ESCC-patients: P = 0.828). Particularly, the achieved postneoadjuvant ypTNM-stage influences the survival probability of patients with EC. Patients with non-CR-T0N+ have a dismal prognosis, and only true pathological complete response with ypT0ypN0 offers superior survival probabilities.

Specifics of Young Gastric Cancer Patients: A Population-Based Analysis of 46,110 Patients with Gastric Cancer from the German Clinical Cancer Registry Group.

Introduction: 2−8% of all gastric cancer occurs at a younger age, also known as early-onset gastric cancer (EOGC). The aim of the present work was to use clinical registry data to classify and characterize the young cohort of patients with gastric cancer more precisely. Methods: German Cancer Registry Group of the Society of German Tumor Centers­Network for Care, Quality and Research in Oncology (ADT)was queried for patients with gastric cancer from 2000−2016. An approach that stratified relative distributions of histological subtypes of gastric adenocarcinoma according to age percentiles was used to define and characterize EOGC. Demographics, tumor characteristics, treatment and survival were analyzed. Results: A total of 46,110 patients were included. Comparison of different groups of age with incidences of histological subtypes showed that incidence of signet ring cell carcinoma (SRCC) increased with decreasing age and exceeded pooled incidences of diffuse and intestinal type tumors in the youngest 20% of patients. We selected this group with median age of 53 as EOGC. The proportion of female patients was lower in EOGC than that of elderly patients (43% versus 45%; p < 0.001). EOGC presented more advanced and undifferentiated tumors with G3/4 stages in 77% versus 62%, T3/4 stages in 51% versus 48%, nodal positive tumors in 57% versus 53% and metastasis in 35% versus 30% (p < 0.001) and received less curative treatment (42% versus 52%; p < 0.001). Survival of EOGC was significantly better (five-years survival: 44% versus 31% (p < 0.0001), with age as independent predictor of better survival (HR 0.61; p < 0.0001). Conclusion: With this population-based registry study we were able to objectively define a cohort of patients referred to as EOGC. Despite more aggressive/advanced tumors and less curative treatment, survival was significantly better compared to elderly patients, and age was identified as an independent predictor for better survival.

Minimally invasivE versus open total GAstrectomy (MEGA): study protocol for a multicentre randomised controlled trial (DRKS00025765).

INTRODUCTION: The only curative treatment for most gastric cancer is radical gastrectomy with D2 lymphadenectomy (LAD). Minimally invasive total gastrectomy (MIG) aims to reduce postoperative morbidity, but its use has not yet been widely established in Western countries. Minimally invasivE versus open total GAstrectomy is the first Western multicentre randomised controlled trial (RCT) to compare postoperative morbidity following MIG vs open total gastrectomy (OG). METHODS AND ANALYSIS: This superiority multicentre RCT compares MIG (intervention) to OG (control) for oncological total gastrectomy with D2 or D2+LAD. Recruitment is expected to last for 2 years. Inclusion criteria comprise age between 18 and 84 years and planned total gastrectomy after initial diagnosis of gastric carcinoma. Exclusion criteria include Eastern Co-operative Oncology Group (ECOG) performance status >2, tumours requiring extended gastrectomy or less than total gastrectomy, previous abdominal surgery or extensive adhesions seriously complicating MIG, other active oncological disease, advanced stages (T4 or M1), emergency setting and pregnancy.The sample size was calculated at 80 participants per group. The primary endpoint is 30-day postoperative morbidity as measured by the Comprehensive Complications Index. Secondary endpoints include postoperative morbidity and mortality, adherence to a fast-track protocol and patient-reported quality of life (QoL) scores (QoR-15, EUROQOL EuroQol-5 Dimensions-5 Levels (EQ-5D), EORTC QLQ-C30, EORTC QLQ-STO22, activities of daily living and Body Image Scale). Oncological endpoints include rate of R0 resection, lymph node yield, disease-free survival and overall survival at 60-month follow-up. ETHICS AND DISSEMINATION: Ethical approval has been received by the independent Ethics Committee of the Medical Faculty, University of Heidelberg (S-816/2021) and will be received from each responsible ethics committee for each individual participating centre prior to recruitment. Results will be published open access. TRIAL REGISTRATION NUMBER: DRKS00025765.

Progressive multifocal leukoencephalopathy associated with chemotherapy induced lymphocytopenia in solid tumors - case report of an underestimated complication.

Background: JC virus reactivation causing progressive multifocal leukoencephalopathy (PML) occurs preferentially in human immunodeficiency virus (HIV) positive individuals or patients suffering from hematologic neoplasms due to impaired viral control. Reactivation in patients suffering from solid malignancies is rarely described in published literature. Case Presentation: Here we describe a case of PML in a male patient suffering from esophageal cancer who underwent neoadjuvant radiochemotherapy and surgical resection in curative intent resulting in complete tumor remission. The radiochemotherapy regimen contained carboplatin and paclitaxel (CROSS protocol). Since therapy onset, the patient presented with persistent and progredient leukopenia and lymphopenia in absence of otherwise known risk factors for PML. Symptom onset, which comprised aphasia, word finding disorder, and paresis, was apparent 7 months after therapy initiation. There was no relief in symptoms despite standard of care PML directed supportive therapy. The patient died two months after therapy onset. Conclusion: PML is a very rare event in solid tumors without obvious states of immununosuppression and thus harbors the risk of unawareness. The reported patient suffered from lymphopenia, associated with systemic therapy, but was an otherwise immunocompetent individual. In case of neurologic impairment in patients suffering from leukopenia, PML must be considered - even in the absence of hematologic neoplasia or HIV infection.

[Robot-assisted Total Gastrectomy with D2 Lymphadenectomy and Intracorporal Reconstruction]. / Robotisch assistierte totale Gastrektomie mit D2-Lymphadenektomie und intrakorporaler Rekonstruktion.

Robot-assisted total gastrectomy for gastric cancer is a demanding operation that is increasingly being performed, not only in Asia but also in specialised centres in Europe. The minimally invasive resection - and above all the lymphadenectomy and the minimally invasive intracorporal reconstruction by oesophagojejunostomy - are technically demanding surgical steps. These techniques are performed internationally in different variations, but have not yet been well standardised. In the video presented, we show the DaVinci Xi-assisted minimally invasive technique of total gastrectomy with D2 lymphadenectomy and intracorporal reconstruction using side-to-side oesophagojejunostomy with linear stapling.

[Complete response after neoadjuvant therapy for esophageal cancer : Implications for surgery]. / Komplettresponse nach neoadjuvanter Therapie beim Ösophaguskarzinom : Implikationen für die Chirurgie.

A relevant number of patients with locally advanced esophageal squamous cell carcinoma and adenocarcinoma show a locoregional complete response of the tumor in the resected material after neoadjuvant therapy with modern chemotherapy and chemoradiation protocols. Due to a high rate of perioperative morbidity and decreased long-term quality of life following esophagectomy, the current treatment algorithm with neoadjuvant therapy and post-neoadjuvant esophagectomy on principle is critically questioned. An individualized treatment algorithm with extended clinical evaluation of post-neoadjuvant remission status and esophagectomy as needed is discussed. Patients with complete remission after neoadjuvant therapy are identified in an extended restaging protocol. Cases of clinical complete remission are treated with an active surveillance concept with esophagectomy as needed, i.e. surgery only when a local tumor recurrence is detected. Retrospective cohort studies have suggested that the active surveillance concept with esophagectomy as needed does not lead to a deterioration of overall survival rates in the patient collective. European prospective randomized, controlled, noninferiority studies with an oncological endpoint are currently evaluating the possibilities of organ-preserving concepts for clinical complete remission of esophageal cancer.

Metastasis and Tumor Cell Migration of Solid Tumors.

The developmental process of local and distant metastases represents the major and defining trait of malignant tumors, whereby tumor cells sustain the capability to migrate from the initial tumor site, seed, and grow at a location other than that of the initial tumor [...].

Postoperative Outcomes of Tangential versus Segmental Resection and End-to-end Reconstruction of the Superior Mesenterico-Portal Vein During Pancreatoduodenectomy for Pancreatic Adenocarcinoma: A Single-Center Experience.

BACKGROUND/AIM: The impact of venous resections and reconstruction techniques on morbidity after surgery for pancreatic cancer (PDAC) remains controversial. PATIENTS AND METHODS: A total of 143 patients receiving pancreatoduodenectomy (PD) for PDAC between 2013 and 2018 were identified from a prospective database. Morbidity and mortality after PD with tangential resection versus end-to-end reconstruction were assessed. RESULTS: Fifty-two of 143 (36.4%) patients underwent PD with portal venous resection (PVR), which was associated with longer operation times [398 (standard error (SE) 12.01) vs. 306 (SE 13.09) min, p<0.001]. PVR was associated with longer intensive-care-unit stay (6.3 vs. 3.8 days, p=0.054); morbidity (Clavien-Dindo classification (CDC) grade IIIa-V 45.8% vs. 35.8%, p=0.279) and 30-day mortality (4.1% vs. 4.2%, p>0.99) were not different. Tangential venous resection was associated with similar CDC grade IIIa-IV (42.9% vs. 50.0%, p=0.781) and 30-day mortality rates (3.5% vs. 4.1%, p=0.538) as segmental resection and end-to-end venous reconstruction. CONCLUSION: Both tangential and segmental PVR appear feasible and can be safely performed to achieve negative resection margins.

Robotic Cancer Surgery.

Cancer kills millions of people around the world every year [...].

Resection of Non-Functional Pancreatic Neuroendocrine Neoplasms-A Single-Center Retrospective Outcome Analysis.

Surgery remains the only curative treatment of pancreatic neuroendocrine neoplasms (pNEN). Here, we report the outcome after surgery for non-functional pNEN at a European Neuroendocrine Tumor Society (ENETS) center in Germany between 2000 and 2019; cases were analyzed for surgical (Clavien-Dindo classification; CDc) and oncological outcomes. Forty-nine patients (tumor grading G1 n = 25, G2 n = 22, G3 n = 2), with a median age of 56 years, were included. Severe complications (CDc ≥ grade 3b) occurred in 11 patients (22.4%) and type B/C pancreatic fistulas (POPFs) occurred in 5 patients (10.2%); in-hospital mortality was 2% (n = 1). Six of seven patients with tumor recurrence (14.3%) had G2 tumors in the pancreatic body/tail. The median survival was 5.7 years (68 months; [1-228 months]). Neither the occurrence (p = 0.683) nor the severity of complications had an influence on the relapse behavior (p = 0.086). This also applied for a POPF (≥B, p = 0.609). G2 pNEN patients (n = 22) with and without tumor recurrence had similar median tumor sizes (4 cm and 3.9 cm, respectively). Five of the six relapsed G2 patients (83.3%) had tumor-positive lymph nodes (N+); all G2 pNEN patients with recurrence had initially been treated with distal pancreatic resection. Pancreatic resections for pNEN are safe but associated with relevant postoperative morbidity. Future studies are needed to evaluate suitable resection strategies for G2 pNEN.

[Current preoperative and perioperative concepts in tumor treatment for locally advanced esophageal carcinoma from a surgical perspective]. / Aktuelle prä- und perioperative Konzepte in der Tumortherapie beim lokal fortgeschrittenen Ösophaguskarzinom aus chirurgischer Perspektive.

Locally advanced esophageal cancer is mostly treated in multimodal therapy protocols according to the current western treatment guidelines. In squamous cell cancer, neoadjuvant chemoradiotherapy is in the foreground. Unimodal surgical and chemoradiation treatment alternatives achieve poorer results for this entity. Surgical salvage resection for tumor recurrence after definitive chemoradiotherapy can be carried out with good oncological results but the frequency of postoperative complications is increased. For locally advanced adenocarcinoma of the esophagus, perioperative chemotherapy and neoadjuvant chemoradiotherapy are two competing level 1 evidence-based treatment concepts that are superior to treatment by surgery alone. The results of head-to-head comparative treatment studies are still pending. A significant number of patients show a complete locoregional remission of the tumor in the surgical specimen after treatment with the modern neoadjuvant protocols. Currently, European prospective randomized noninferiority studies with an oncological endpoint are testing the possibilities of organ-retaining concepts in clinical complete remission (surgery as needed; watch and wait). For the future, it is to be expected that the curative treatment results of locally advanced esophageal carcinoma will again significantly improve, in particular through the additional possibilities of immunotherapy and organ-preserving therapy concepts for postneoadjuvant complete remission.