The Impact of Signet Ring Cell Differentiation on Outcome in Patients with Esophageal and Gastroesophageal Junction Adenocarcinoma.

BACKGROUND: Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC. METHODS: Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group. RESULTS: Overall, 129 (19%) of 689 patients included had SRCs (nCT: n = 64; nCRT: n = 65). The SRC group had a more advanced ypT stage (p = 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range [IQR]) 2 [0-5] vs. 1 [0-3]; p = 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%; p = 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median [IQR] 12 [5-50] vs. 23 [8-164]; p = 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT. CONCLUSIONS: SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.

Neoadjuvant chemotherapy or chemoradiotherapy for adenocarcinoma of the esophagus.

BACKGROUND: The optimal treatment strategy for patients with esophageal adenocarcinoma (EAC) remains undetermined. This study compared outcomes in patients undergoing neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) for EAC. METHODS: Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000-2017) and included. After propensity score matching, the impact of the treatments on postoperative complications, in-hospital mortality, pathological outcomes, and survival rates were compared. RESULTS: Of the 396 eligible patients, 262 patients were analysed following matching with 131 patients in both groups. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in-hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs 83%, P = 0.013), and higher pathological complete response rates (15% vs 5%, P < 0.001). No differences in 5-year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645) were found. CONCLUSION: In this study no differences between nCT and nCRT were seen in postoperative complications and in-hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.

Long-term Health-related Quality of Life Following Esophagectomy: A Nonrandomized Comparison of Thoracoscopically Assisted and Open Surgery.

OBJECTIVE: The aim of this study was to assess long-term health-related quality of life (HRQL) in patients after thoracoscopic and open esophagectomy. SUMMARY OF BACKGROUND DATA: Trials comparing minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes; however, long-term HRQL data are lacking. This prospective nonrandomized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy (TAMK) and open transthoracic Ivor Lewis esophagectomy (TTIL) for esophageal or gastroesophageal junction (GEJ) cancer. METHODS: Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessments for up to 24 months using the EORTC generic and disease-specific measures, QLQ-C30 and QLQ-OES18. Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score (generated by boosted regression) adjustment. RESULTS: Of the 487 patients, 377 underwent TAMK and 110 underwent TTIL. Most clinical variables were similar in the 2 groups; however, there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK (54% vs 32%, P < 0.01) and this was reflected in the survival data.Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively (P = 0.036). In addition, mean constipation scores were significantly higher for the TTIL group, with a 15-point difference in mean score at 3 months postoperatively (P = 0.037). CONCLUSIONS: This large comprehensive nonrandomized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK.

Thoracoscopic-assisted esophagectomy for esophageal cancer: analysis of patterns and prognostic factors for recurrence.

OBJECTIVE: The authors report the recurrence pattern of esophageal cancer after thoracoscopic-assisted esophagectomy (TAE), comparing it to the recurrence pattern after open surgery and identify prognostic factors for recurrence. SUMMARY OF BACKGROUND DATA: To improve long-term survival for esophageal cancer radical surgery has been proposed increasingly, however, recurrent disease remains a problem. Opinion is divided as to the adequacy of resection possible using minimally invasive techniques with concerns that there may be an increased incidence in locoregional recurrence. METHODS: A total of 221 patients who underwent esophagectomy at the Princess Alexandra Hospital without any neoadjuvant or adjuvant therapy were identified from a prospective database. Patients were followed up for the detection of symptomatic recurrence for a median of 59 months. RESULTS: Within this group 165 patients underwent TAE and 56 an open transthoracic esophagectomy (TTE). The 5-year overall recurrence rate was 133/221 (60%). The 5-year rates of symptomatic first recurrence following TAE was 4%, 9%, and 47% for local, regional, and distant recurrence, respectively. The 5-year rates of symptomatic first recurrence following TTE was 5%, 18%, and 55% for local, regional, and distant recurrence, respectively. Operative approach was not a prognostic factor for any type of recurrence. Independent prognostic factors associated with locoregional recurrence were positive margins and number of positive nodes. Distant recurrence was associated with T stage, differentiation, tumor length >6 cm, and number of positive nodes. CONCLUSION: Distant recurrence remains a significant problem in esophageal cancer. TAE achieved adequate locoregional control and compared favorably with open TTE.

Assessment of morbidity following regional nodal dissection in the axilla and groin for metastatic melanoma.

BACKGROUND: This study assessed and compared the morbidity of nodal dissection in the axilla and groin including sentinel lymph node biopsy (SLNB), completion lymph node dissection for a positive SLNB (CLND) and therapeutic lymph node dissection (TLND) with and without adjuvant radiotherapy (RT). METHODS: Patients who had nodal dissection in the axilla or groin for cutaneous melanoma over an 18-year period (1995-2013) were prospectively documented on a database. The median follow-up was nearly 3 years. Early complications and clinically relevant lymphoedema were retrospectively analysed to assess the incidence and differences between the region and type of nodal surgery. RESULTS: Included were 1521 patients following nodal dissection in the axilla (916 patients) and groin (605 patients). Less early complications occurred following SLNB in the axilla compared with the groin (5% versus 14%, P = 0.0001). Early complications were similar for CLND and TLND in the groin (49% versus 43%, P = 0.879) and axilla (28% versus 33%, P = 0.607). Moderate to severe lymphoedema rates were similar following axillary SLNB and CLND (6% versus 8%, P = 0.407). The lymphoedema rate for groin SLNB was lower than CLND (10% versus 20%, P = 0.063). No significant difference in lymphoedema rates followed CLND and TLND in each region. Following TLND, RT increased lymphoedema rates. CONCLUSIONS: Morbidity may occur following SLNB with the groin having a higher rate of early complications and lymphoedema compared with the axilla. The morbidity following CLND and TLND were similar. Lymphoedema rates were increased following RT.

Melanoma brain metastases: the impact of nodal disease.

Brain metastases (BMs) are a major source of mortality and morbidity in patients with melanoma. This study assesses prognostic nodal factors in patients with nodal metastatic melanoma with respect to the development of BMs. The aim was to identify a high risk subset that may benefit from brain directed management. Prospective surgical and clinical trial databases identified patients who had had nodal dissections and were seen through the Princess Alexandra Hospital Melanoma clinic between August 1995 and June 2010. Patient data was collected and event data was updated from medical imaging and clinical records. The primary endpoint was the rate of development of BMs. 474 patients were identified as having nodal dissections. Two hundred and eighty-seven patients (61%) were male with a median age of 52 (39-66). The most common nodal dissection site was axilla 190 (40%), followed by groin 154 (32.5%) and neck 130 (27.5%). Adjuvant radiotherapy to the nodal basin was delivered to 134 patients (28%). BMs occurred in 61 patients (12.9%) with a median time of 13.87 months from dissection. No lymph node characteristics were significantly associated with the development of BMs including: nodal region (p=0.72), nodal size (p=0.08), number of involved nodes (p=0.36), presence of extra-capsular spread (p=0.47) and AJCC N stage. There was no significant association between primary ulceration (p=0.37) or location and development of BMs. It appears that for patients with resected stage III melanoma there is no histopathological lymph node feature associated with the development of BMs. This highlights the importance of identifying molecular markers in nodal melanoma which may predict for BMs to further direct site-specific therapy.

Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial.

INTRODUCTION: Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction. METHODS: Patients were randomised to receive preoperative CT with cisplatin (80 mg/m(2)) and infusional 5 fluorouracil (1000 mg/m(2)/d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m(2)/d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life. RESULTS: Seventy-five patients were enrolled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively (p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT (p = 0.83). CONCLUSIONS: Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.

Comparison of the outcomes between open and minimally invasive esophagectomy.

OBJECTIVE: We report patient outcomes from esophageal resection with respect to morbidity and cancer survival comparing open thoracotomy and laparotomy (Open), with a thoracoscopic/laparotomy approach (Thoracoscopic-Assisted) and a total thoracoscopic/laparoscopic approach (Total MIE). METHODS: From a prospective database of all patients managed with cancer of the esophagus or esophagogastric junction, patients who had a resection using one of three techniques were analyzed to assess postoperative variables, adequacy of cancer clearance, and survival. RESULTS: The number of patients for each procedure was as follows: Open, 114; Thoracoscopic-Assisted, 309; and Total MIE, 23. The groups were comparable with respect to preoperative variables. The differences in the postoperative variables were: less median blood loss in the Thoracoscopic-Assisted (400 mL) and Total MIE (300 mL) groups versus Open (600 mL); longer time for Total MIE (330 minutes) versus Thoracoscopic-Assisted (285 minutes) and Open (300 minutes); longer median time in hospital for Open (14 days) versus Thoracoscopic-Assisted (13 days), Total MIE (11 days) and less stricture formation in the Open (6.1%) versus Thoracoscopic-Assisted (21.6%), Total MIE (36%). There were no differences in lymph node retrieval for each of the approaches. Open had more stage III patients (65.8%) versus Thoracoscopic-Assisted (34.4%), Total MIE (52.1%). There was no difference in survival when the groups were compared stage for stage for overall median or 3-year survival. CONCLUSION: Minimally invasive techniques to resect the esophagus in patients with cancer were confirmed to be safe and comparable to an open approach with respect to postoperative recovery and cancer survival.