Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis.

BACKGROUND: Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. METHODS: All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. RESULTS: Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. CONCLUSION: This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women.

Improved radiologic diagnosis of delayed gastric conduit emptying (DGCE) after esophagectomy using a functional upper gastrointestinal contrast study.

BACKGROUND: With increasing incidence of esophageal cancer, a growing number of patients are at risk of developing delayed gastric conduit emptying (DGCE) in the early postoperative phase after esophagectomy. This condition is of great postoperative concern due to its association with adverse outcomes. PURPOSE: To give a narrative review of the literature concerning radiological diagnosis of DGCE after esophagectomy and a proposal for an improved, functional protocol with objective measurements. MATERIAL AND METHODS: The protocol was designed at Virginia Mason Medical Center in Seattle and is based on the Timed Barium Esophagogram (TBE) concept, which has been adapted to assess the passage of contrast from the gastric conduit into the duodenum. RESULTS: The literature review showed a general lack of standardization and scientific evidence behind the use of radiology to assess DGCE. We found that our proposed standardized upper gastrointestinal (UGI) contrast study considers both the time aspect in DGCE and provides morphologic information of the gastric conduit. This radiological protocol was tested on 112 patients in a trial performed at two high-volume centers for esophageal surgery and included an UGI contrast study 2-3 days postoperatively. The study demonstrated that this UGI contrast study can be included in the standardized clinical pathway after esophagectomy. CONCLUSION: This new, proposed UGI contrast study has the potential to diagnose early postoperative DGCE in a standardized manner and to improve overall patient outcomes after esophagectomy.

Management and outcomes in a consecutive series of patients with aero-digestive fistula at a tertiary gastro-esophageal surgery center.

Aerodigestive fistula (ADF) is defined as a pathological connection between the upper digestive tract and the airway. ADF is associated with high morbidity and mortality and management is often complex. A cohort study including all patients admitted with ADF 2004-2022 at a single tertiary esophageal surgery center was performed based on prospectively collected administrative data and retrospectively collected electronic patient chart data,. Patient demographics, performance status, comorbidity, fistula characteristics, management, and outcomes in terms of morbidity and mortality were assessed in patients with ADF of three distinct types: (i) tumor overgrowth-related, (ii) various benign etiologies, and (iii) post-esophagectomy. Sixty-one patients with ADF were included in the study, 33 (54.1%) tumor overgrowth-related, six (9.8%) benign and 22 (36.1%) post-esophagectomy. In the post-esophagectomy group 15 out of 22 (68.2%) patients were diagnosed with anastomotic leakage prior to ADF diagnosis. Self-expandable metallic stents (SEMS) were used for temporary fistula sealing in 59 out of 61 (96.7%) patients, of which most received stents in both the digestive tract and airway. Temporary fistula sealing with stents was successful enabling discharge from hospital in 47 out of 59 (79.7%) patients. Definitive ADF repair was performed in 16 (26.2%) patients, of which one (6.3%) died within 90-days and 15 could be discharged home with permanently sealed fistulas. ADF is a complex condition associated with high mortality, which often requires multiple advanced interventions. SEMS can be applied in the airway and simultaneously in the digestive tract to temporarily seal the ADF as bridge to definitive surgical repair.

CRP as an early indicator for anastomotic leakage after esophagectomy for cancer: a single tertiary gastro-esophageal center study.

PURPOSE: To determine the relationship between postoperative C-reactive protein (CRP) as an early indicator of anastomotic leakage (AL) after esophagectomy for esophageal cancer. METHODS: We reviewed patients diagnosed with esophageal or esophagogastric junctional cancer who underwent esophagectomy between 2006 and 2022 at the Karolinska University Hospital, Stockholm, Sweden. Multivariable logistic regression models estimated relative risk for AL by calculating the odds ratio (OR) with a 95% confidence interval (CI). The cut-off values for CRP were based on the maximum Youden's index using receiver operating characteristic curve analysis. RESULTS: In total, 612 patients were included, with 464 (75.8%) in the non-AL (N-AL) group and 148 (24.2%) in the AL group. Preoperative body mass index and the proportion of patients with the American Society of Anesthesiologists physical status classification 3 were significantly higher in the AL group than in the N-AL group. The median day of AL occurrence was the postoperative day (POD) 8. Trends in CRP levels from POD 2 to 3 and POD 3 to 4 were significantly higher in the AL than in the N-AL group. An increase in CRP of ≥ 4.65% on POD 2 to 3 was an independent risk factor for AL with the highest OR of 3.67 (95% CI 1.66-8.38, p = 0.001) in patients with CRP levels on POD 2 above 211 mg/L. CONCLUSION: Early changes in postoperative CRP levels may help to detect AL early following esophageal cancer surgery.

Effects of neoadjuvant therapy on health-related quality of life for patients with gastroesophageal cancer.

BACKGROUND: Neoadjuvant therapy in combination with surgery increases survival in gastroesophageal cancer; however, little is known about its impact on health-related quality of life. This study compared the impact of neoadjuvant therapy with that of surgery alone on the health-related quality of life in patients treated for gastroesophageal cancer. METHODS: A single-centre cohort study with prospectively collected data from patients undergoing curative intended treatment for gastroesophageal cancer between 2013 and 2020 was performed. Health-related quality of life was assessed prior to surgery and patients stratified according to neoadjuvant therapy or surgery alone. The primary endpoint was self-assessed health-related quality of life, evaluated using validated cancer-specific questionnaires. A pre-specified multivariable model adjusted for age, ASA score, and clinical T- and N-stage was used. RESULTS: A total of 361 patients were included, of whom 239 (61%) were treated with neoadjuvant therapy. Patients treated with neoadjuvant therapy reported less difficulties with eating restrictions (-11.9, p = 0.005), pain (-10.9, p = 0.004), and insomnia (-12.6, p = 0.004) than patients treated with surgery alone. Patients with oesophageal cancer and neoadjuvant therapy reported less dysphagia (-16.6, p < 0.001), eating restrictions (-23.2, p < 0.001), and odynophagia (-18.0, p = 0.002) than those who underwent surgery alone. CONCLUSION: Neoadjuvant therapy was associated with a significant reduction in symptoms affecting malnutrition and improved health-related quality of life in patients with gastroesophageal cancer. These results indicates that more patients might be available for neoadjuvant therapy, despite the baseline burden of gastroesophageal cancer.

Neoadjuvant Chemoradiotherapy Versus Chemotherapy for the Treatment of Locally Advanced Esophageal Adenocarcinoma in the European Multicenter ENSURE Study.

OBJECTIVE: This study aimed to compare clinicopathologic, oncologic, and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. BACKGROUND: nCT and nCRT are the standards of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated the superiority of either approach. METHODS: ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009-2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. RESULTS: A total of 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% ( P <0.001), with R0 in 78.2% and 94.2% ( P <0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased [hazard ratio (HR)=2.73, 95% CI: 1.43-5.21, P= 0.002] following nCRT versus nCT. Probability of local recurrence was reduced (odds ratio=0.71, 95% CI: 0.54-0.93, P =0.012), and distant recurrence-free survival time reduced (HR=1.18, 95% CI: 1.02-1.37, P =0.023) after nCRT versus nCT, with no difference in OS among all patients (HR=1.10, 95% CI: 0.98-1.25, P =0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median: 60.7 months, 95% CI: 49.5-71.8 vs 40.8 months, 95% CI: 42.8-53.4, P <0.001). CONCLUSIONS: In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence-free survival for patients with LAEC, without differences in OS. These data support tailored patient-specific decision-making in the overall approach to achieving optimum outcomes in LAEC.

Impact of Laparoscopic Gastrectomy on the Completion Rate of the Perioperative Chemotherapy Regimen in Gastric Cancer: A Swedish Nationwide Study.

BACKGROUND: Omission of prescheduled chemotherapy following surgery for gastric cancer is a frequent clinical problem. This study examined whether laparoscopic gastrectomy (LG) had a positive impact on compliance with adjuvant chemotherapy compared with open (OG). METHODS: Patients with cT2-4aN0-3M0 adenocarcinoma treated with gastrectomy and perioperative chemotherapy between 2015 and 2020 were identified in the Swedish national register. Additional information regarding chemotherapy was retrieved from medical records. Regression models were used to investigate the association between surgical approach and the following outcomes: initiation of adjuvant chemotherapy, modification, and time interval from surgery to start of treatment. RESULTS: A total of 247 patients were included (121 OG and 126 LG, conversion rate 11%), of which 71.3% had performance status ECOG 0 and 77.7% clinical stage II/III. In total, 86.2% of patients started adjuvant chemotherapy, with no significant difference between the groups (LG 88.1% vs OG 84.3%, p = 0.5). Reduction of chemotherapy occurred in 37.4% of patients and was similar between groups (LG 39.4% vs OG 35.1%, p = 0.6), as was the time interval from surgery. In multivariable analysis, LG was not associated with the probability of starting adjuvant chemotherapy (OR 1.36, p = 0.4) or the need for reduction (OR 1.29, p = 0.4). Conversely, major complications had a significant, negative impact on both outcomes. CONCLUSIONS: This nationwide study demonstrated a high rate of adjuvant chemotherapy initiation after curative intended surgery for gastric cancer. A beneficial effect of LG compared with OG on the completion rate was not evident.

Postoperative complications after esophagectomy for cancer, neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy: A single institutional cohort study.

Background: Complications after esophagectomy are common and the possible increase in postoperative complications associated with neoadjuvant chemoradiotherapy is of concern. The aim of our study was to analyze if the addition of radiotherapy to neoadjuvant chemotherapy increases the incidence and severity of postoperative complications, including evaluation of the relation between radiation doses to the heart and lungs and postoperative complications. Methods: The study was based on an institutional surgical database for esophageal cancer. The study period was October 2008 to March 2020. Patients treated with neoadjuvant chemoradiotherapy were compared to patients treated with neoadjuvant chemotherapy and dose/volume parameters for the lungs and heart considered. The primary outcome was 30-day postoperative complications. Results: During the study period, 274 patients underwent surgery for esophageal cancer, 93 patients after neoadjuvant chemotherapy and 181 patients after neoadjuvant chemoradiotherapy. The median prescribed radiation dose to the planning target volume was 41.4 Gy, the median of the mean lung dose was 6.2 Gy, and the median of the mean heart dose was 20.3 Gy. The addition of radiotherapy to neoadjuvant chemotherapy did not increase the incidence of postoperative complications. Neither were radiation doses to the lungs and heart associated with postoperative complications. Taxane-based chemotherapy regimens were however associated with an increased incidence of postoperative complications. Conclusions: In our cohort, the addition of neoadjuvant radiotherapy to chemotherapy was not associated with postoperative complications. However, taxane-based chemotherapy regimens, with or without concomitant radiotherapy, were associated with postoperative complications.

Improved survival after laparoscopic compared to open gastrectomy for advanced gastric cancer: a Swedish population-based cohort study.

BACKGROUND: Laparoscopic gastrectomy is increasingly used for the treatment of locally advanced gastric cancer but concerns remain whether similar results can be obtained compared to open gastrectomy, especially in Western populations. This study compared the short-term postoperative, oncological and survival outcomes following laparoscopic versus open gastrectomy based on data from the Swedish National Register for Esophageal and Gastric Cancer. METHODS: Patients who underwent surgery with curative intent for adenocarcinoma of the stomach or gastroesophageal junction Siewert type III from 2015 to 2020 were identified, and 622 patients with cT2-4aN0-3M0 tumors were included. The impact of surgical approach on short-term outcomes was assessed using multivariable logistic regression. Long-term survival was compared using multivariable Cox regression. RESULTS: In total, 350 patients underwent open and 272 laparoscopic gastrectomy, of which 12.9% were converted to open surgery. The groups were similar regarding distribution of clinical disease stage (27.6% stage I, 46.0% stage II, and 26.4% stage III). Neoadjuvant chemotherapy was administered to 52.7% of the patients. There was no difference in the rate of postoperative complications, but laparoscopic approach was associated with lower 90 day mortality (1.8 vs 4.9%, p = 0.043). The median number of resected lymph nodes was higher after laparoscopic surgery (32 vs 26, p < 0.001), while no difference was found in the rate of tumor-free resection margins. Better overall survival was observed after laparoscopic gastrectomy (HR 0.63, p < 0.001). CONCLUSIONS: Laparoscopic gastrectomy can be safely preformed for advanced gastric cancer and is associated with improved overall survival compared to open surgery.

Risk factors for acute kidney injury after pancreatoduodenectomy, and association with postoperative complications and death.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality after general surgery, although little is known among patients undergoing pancreatoduodenectomy. The objective was to investigate the association between AKI and postoperative complications and death after pancreatoduodenectomy. METHODS: All patients ≥18 years who underwent a pancreatoduodenectomy 2008-2019 at the Karolinska University Hospital, Stockholm, Sweden, were included. Standardized criteria for AKI, including estimated glomerular filtration rate (eGFR) and urine volume measurements, were used to grade postoperative AKI. RESULTS: In total, 970 patients were included with a median age of 68 years (IQR 61-74) of whom 517 (53.3%) were men. There were 137 (14.1%) patients who developed postoperative AKI. Risk factors for AKI included lower preoperative eGFR, cardiovascular disease and treatment with renin-angiotensin system inhibitors or diuretics. Those who developed AKI had a higher risk of severe postoperative complications, including Clavien-Dindo score ≥ IIIa (adjusted OR 3.35, 95% CI 2.24-5.01) and ICU admission (adjusted OR 7.83, 95% CI 4.39-13.99). In time-to-event analysis, AKI was associated with an increased risk for both 30-day mortality (adjusted HR 4.51, 95% CI 1.54-13.27) and 90-day mortality (adjusted HR 4.93, 95% CI 2.37-10.26). Patients with benign histology and AKI also had an increased 1-year mortality (HR 4.89, 95% CI 1.88-12.71). CONCLUSIONS: Postoperative AKI was associated with major postoperative complications and an increased risk of postoperative mortality. Monitoring changes in serum creatinine levels and urine volume output could be important in the immediate perioperative period to improve outcomes after pancreatoduodenectomy.

Frequency of blood lactate elevation following esophagectomy and its association to postoperative complications.

BACKGROUND: Esophagectomy is a major surgical intervention and a cornerstone in the treatment of esophageal cancer. There is clinical experience that blood lactate concentration often is elevated in the period following esophagectomy, but the incidence and clinical consequences are sparsely studied. METHODS: We extracted data from all patients undergoing esophagectomy at Karolinska University Hospital 2016-2018, n = 153. Most were performed with minimally invasive technique, n = 130. Blood lactate values directly after surgery, highest value during the first night, and morning level on postoperative day one were recorded. Primary outcome was hospital length of stay and secondary outcome was a composite of postoperative infection, additional surgery, or intensive care during the hospital stay. Development of anastomotic leak was analyzed separately. RESULTS: Postoperative hyperlactatemia was common as 93% of patients had peak lactate concentration >1.6 mmol/L and 27% >3.5 mmol/L in the first night following operation. Median hospital length of stay was 14 days. Blood lactate showed a weak correlation to hospital stay and intensive care the morning following surgery, but not at arrival to postoperative ward. There were no statistical differences between those with and without anastomotic leak at any of the time points. Elevated lactate in the first 12-16 h postoperatively was related to surgical factors (open technique, surgery time, and perioperative bleeding) but not to patient related factors (ASA-class, Charlson comorbidity index, sex, age) or cumulative fluid balance. CONCLUSION: In conclusion, elevated blood lactate in the immediate time following esophagectomy showed a weak association to intensive care and length of stay but not anastomotic leak.

An International Multicenter Study Exploring Whether Surveillance After Esophageal Cancer Surgery Impacts Oncological and Quality of Life Outcomes (ENSURE).

OBJECTIVE: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer. SUMMARY BACKGROUND DATA: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence. METHODS: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed. RESULTS: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL. CONCLUSIONS: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.

Minimally invasive surgical techniques for oesophageal cancer and nutritional recovery: a prospective population-based cohort study.

OBJECTIVES: To explore whether the minimally invasive oesophagectomy (MIE) or hybrid minimally invasive oesophagectomy (HMIE) are associated with better nutritional status and less weight loss 1 year after surgery, compared with open oesophagectomy (OE). DESIGN: Prospective cohort study. SETTING: All patients undergoing oesophagectomy for cancer in Sweden during 2013-2018. PARTICIPANTS: A total of 424 patients alive at 1 year after surgery were eligible, and 281 completed the 1-year assessment. Of these, 239 had complete clinical data and were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was nutritional status at 1 year after surgery, assessed using the abbreviated Patient-Generated Subjective Global Assessment questionnaire. The secondary outcomes included postoperative weight loss at 6 months and 1 year after surgery. RESULTS: Of the included patients, 78 underwent MIE, 74 HMIE while 87 patients underwent OE. The MIE group had the highest prevalence of malnutrition (42% vs 22% after HMIE vs 25% after OE), reduced food intake (63% vs 45% after HMIE vs 39% after OE), symptoms reducing food intake (60% vs 45% after HMIE vs 60% after OE) and abnormal activities/function (45% vs 32% after HMIE vs 43% after OE). After adjustment for confounders, MIE was associated with a statistically significant increased risk of reduced food intake 1 year after surgery (OR 2.87, 95% CI 1.47 to 5.61), compared with OE. Other outcomes were not statistically significantly different between the groups. No statistically significant associations were observed between surgical techniques and weight loss up to 1 year after surgery. CONCLUSIONS: MIE was statistically significantly associated with reduced food intake 1 year after surgery. However, no differences were observed in weight loss between the surgical techniques. Further studies on nutritional impact of surgical techniques in oesophageal cancer are needed.

Analysis of Compliance with Enhanced Recovery After Surgery (ERAS) Protocol for Esophagectomy.

BACKGROUND: ERAS guidelines have provided an effective recovery approach for esophagectomy. This study aimed to identify the relationship between the length of hospital stay (LOS) and compliance with clinical benchmarks of an established institutional ERAS program. METHODS: A single-center prospective database of esophageal cancer patients was retrospectively analyzed between January 2016 and January 2020. All patients underwent surgery within a standardized ERAS pathway for esophagectomy. Compliance with individual ERAS benchmarks and postoperative outcomes were evaluated according to patient's LOS; accelerated (≤ 6 days, AR), targeted (7-8 days, TR), and delayed recovery (≥ 9 days, DR). RESULTS: The study included 100 consecutive patients undergoing esophagectomy with a median LOS of 7 (3.8-40.8) days, and a 30-day readmission rate of 12.6%. LOS was not affected by comorbidities, tumor type or stage, neoadjuvant therapy, operative approach or anastomotic leak. Postoperative complications were 49.5%, and 90-day mortality was 3.8%. AR, TR, and DL were achieved by 45%, 31%, and 24% of patients, respectively. Postoperative morbidity differed significantly among groups, impacting LOS (p < 0.001). Overall compliance with ERAS protocol was 82.7% and adherence to specific benchmarks was initially (< 48 h) high, but significantly affected by postoperative complications afterwards. CONCLUSIONS: Adherence to recovery benchmarks in patients undergoing esophagectomy is most commonly impacted by postoperative complications. In esophageal cancer surgery, the adherence to ERAS benchmarks after esophagectomy should be regularly audited. Modification to ERAS protocols to increase application in patients with complications should be considered.

Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial.

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04460352.

Impact of Early Jejunostomy Tube Feeding on Clinical Outcome and Parameters of Body Composition in Esophageal Cancer Patients Receiving Multimodal Therapy.

BACKGROUND: Malnutrition commonly affects patients with esophageal cancer and has the potential to negatively influence treatment outcomes. The aim of this study was to investigate the impact of early (preoperative) jejunostomy tube feeding (JTF) in nutritionally 'high risk' patients receiving multimodal therapy for esophageal cancer. METHODS: Patients were selected to undergo early JTF during neoadjuvant chemoradiotherapy (nCRT) in accordance with European Society for Clinical Nutrition and Metabolism (ESPEN) and Enhanced Recovery after Surgery (ERAS®) Society guidelines. Clinical outcomes were compared with patients who received routine JTF from the time of esophagectomy. Body composition was determined from computed tomography (CT) images acquired at diagnosis, after nCRT, and ≥ 3 months after surgery. RESULTS: In total, 81 patients received early JTF and 91 patients received routine JTF. Patients who received early JTF had lower body mass index (BMI; 26.1 ± 4.6 vs. 28.4 ± 4.9; p = 0.002), greater weight loss, and worse performance status at diagnosis. Groups were otherwise well-matched for baseline characteristics. Rate of re-intubation (8.8% vs. 1.1%; p = 0.027), pulmonary embolism (5.0% vs. 0.0%; p = 0.046), and 90-day mortality (10.0% vs. 1.1%; p = 0.010) were worse in the early JTF group; however, overall survival was equivalent for both the early and routine JTF groups (p = 0.053). Wide variation in the degree of preoperative muscle loss and total adipose tissue loss was observed across the entire study cohort. Relative preoperative muscle and adipose tissue loss in patients with early and routine JTF was equivalent. CONCLUSIONS: In patients determined to be at 'high risk' of malnutrition, early JTF may prevent excess morbidity after esophagectomy with an associated relative preservation of parameters of body composition.

A 68Ga-FAPI-46 PET/CT Imaging Pitfall in Assessing Residual Gastric Cancer Early After Chemotherapy.

ABSTRACT: After neoadjuvant chemotherapy, preoperative imaging with 68Ga-FAPI-46 PET/CT showed a similar level of tracer uptake at the location of the primary tumors in 2 patients with gastric cancer. Postoperative histopathology revealed residual malignant cells only in one of the patients, whereas the elevated FAPI uptake in the other patient correlated to an inflammatory reaction and fibrosis. With this case, we would like to highlight that an increased FAPI uptake in inflammatory and fibrotic tissue early after chemotherapy may represent a potential interpretation pitfall. Further studies evaluating the clinical application of FAPI-PET in assessing residual cancer tissue are warranted.