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.

Patients with in-transit melanoma metastases have comparable survival outcomes following isolated limb infusion or intralesional PV-10-A propensity score matched, single center study.

BACKGROUND AND OBJECTIVE: Isolated limb infusion (ILI) and intralesional PV-10 are well described locoregional therapies for in-transit melanoma. The objective of this study was to assess the effect of these treatments on survival outcomes within a cohort matched for key characteristics. METHODS: Patients were treated using ILI or intralesional PV-10 at a single institution and the data prospectively recorded. Propensity score matching was performed using key covariates within a logistic regression model. The primary outcome was the melanoma-specific survival. RESULTS: Seventy-two patients nonrandomized were successfully matched. Both treatments produced similar best overall responses. The median melanoma-specific survival (MSS) was 74.4 months from ILI and 36.4 months from PV-10 treatments (P = 0.164). Within the ILI subgroup, the 12-, 24-, 36- and 60-month MSS rates were 85.3%, 75.3%, 60.1%, and 60.1%, respectively. From the time of PV-10 the corresponding 12-, 24-, 36-, and 60-month MSS rates were 82.6%, 70.0%, 53.9%, and 35.9%. On multivariate analysis, there was a significant difference in survival comparing completely with noncomplete responders ( P = 0.031). CONCLUSIONS: These findings demonstrate that ILI and PV-10 treatments for in-transit disease produce comparable long-term survival. Both therapies have reproducible response rates and predominantly localized and tolerable side-effects.

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study.

BACKGROUND: Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease. METHODOLOGY: An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions. RESULTS: Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03). CONCLUSIONS: Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

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.

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma.

BACKGROUND: In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. METHODS: An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy. RESULTS: Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis (CR 33.3%, PR 53.3%, SD 6.7%). The median follow up duration was 19.25 months. Size of metastases (<10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events. CONCLUSIONS: The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects.

Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival.

Patterns of Recurrence in Patients with Stage IIIB/C Cutaneous Melanoma of the Head and Neck Following Surgery With and Without Adjuvant Radiation Therapy: Is Isolated Regional Recurrence Salvageable?

BACKGROUND: Understanding recurrence patterns is vital for guiding treatment. This study describes recurrence patterns for patients with stage IIIB/C head and neck melanoma (HNM) after therapeutic lymph node dissection (TLND) ± adjuvant radiation therapy (RT). We also report outcomes for salvage therapy for patients with isolated regional relapse. METHODS AND MATERIALS: A single-institution prospective database of 173 patients with American Joint Committee on Cancer (AJCC) stage IIIB/C HNM undergoing TLND between 1997 and 2012 was retrospectively reviewed. Timing and patterns of recurrence were reviewed. Univariable and multivariable analyses were undertaken using the Kaplan-Meier and Cox regression methods to determine factors predictive of recurrence. Median follow-up was 32 months. RESULTS: Adjuvant RT was administered to 66/173 (38 %) patients. Patients selected for RT had a higher AJCC stage and had more extracapsular invasion. The 5-year distant, cervical nodal and in-transit recurrence rates were 38, 10, and 13 %, respectively, following surgery alone compared with 60, 17, and 31 %, respectively, for the adjuvant RT group. The head and neck regional 5-year recurrence rate (combining in-basin nodal and in-transit) was 23 % for the entire cohort. Isolated cervical recurrence occurred in 19 patients: 17/19 underwent salvage surgery (10/17 patients received RT after salvage surgery) and 2/19 had RT alone. However, distant recurrence occurred in 12/19 salvage patients, with most occurring within 12 months, while 4/19 were disease free. CONCLUSIONS: Using a selective approach for adjuvant RT, isolated cervical recurrence after TLND is uncommon. Isolated cervical recurrence can be salvaged effectively with further local therapy; however, distant disease frequently follows.

Treatment results of curative gastric resection from a specialist Australian unit: low volume with satisfactory outcomes.

BACKGROUND: The incidence of gastric cancer is decreasing in Australia, yet it remains a common cause of cancer-related mortality. Surgical resection remains the cornerstone of curative treatment. High-volume specialized units have reported superior perioperative and oncological outcomes. The role of D2 lymphadenectomy has been controversial as a result of concerns over increased morbidity. Our aim is to report the perioperative and oncological outcomes of curative gastric resection from a specialist Australian upper GI unit. METHODS: Data from a prospectively maintained database were reviewed for all patients undergoing curative resection for gastric adenocarcinoma from a single unit during a 12-year period. Perioperative and long-term outcomes were compiled. RESULTS: There were 255 curative gastric resections during 12 years. An R0 resection was performed in 96 % with a perioperative mortality rate of 1.6 %. A D2 dissection was performed in 85 % of cases in the past 6 years, with no increase in perioperative morbidity or mortality detected. The 5-year overall survival was 53 %. CONCLUSION: Our results demonstrate that both short- and long-term outcomes of surgical resection in gastric cancer patients, comparable to international high-volume centers, can be achieved in an Australian upper GI unit. A D2 lymph node dissection can be performed safely without any increase in perioperative risk in a specialist unit that has the necessary training but also the perioperative support structures to manage these complex patients.

Right-sided diaphragmatic hernia causing gastric outlet obstruction 1 month after trauma.

Diaphragmatic hernias arising from trauma are rare, and scarcely present in a delayed manner. This case report highlights a case of delayed presentation of a right-sided post-traumatic hernia in a woman in her early 70s following a fall. The aim of this report is to shed light on the diagnostic peculiarities and management. The woman presented with a 3-day history of abdominal pain and coffee-ground vomiting. This followed a fall a month ago. CT confirmed the diagnosis of a gastric outlet obstruction secondary to a right-sided diaphragmatic rupture. At surgery, the herniated abdominal contents were reduced, and the diaphragmatic defect was fixed. The postoperative recovery was unremarkable, and the patient was discharged on day 4. This case highlights that diaphragmatic hernias should be considered as differential diagnoses following recent trauma.

Achieving a textbook outcome in patients undergoing gastric resections in a low incidence, high-volume Australian Upper GI unit.

BACKGROUND: Textbook outcome (TBO) has been proposed as a composite measure of quality in esophagogastric surgery, and achieving a TBO has been associated with improved overall survival (OS). The Dutch Upper Gastrointestinal Cancer Audit group determined their TBO rate for gastrectomy to be 32.1%, using 10 parameters. Our study aimed to assess the TBO rate in patients who had a gastrectomy for cancer in an Australian Upper GI unit, allowing for comparisons with international specialist centers. METHODS: Retrospective analysis of a prospectively maintained database of patients who had a gastrectomy for cancer performed by the surgeons in a single Australian center between 2013 and 2018. Postoperative complications were analyzed using Clavien-Dindo (CD) ≥2 and CD ≥3 definitions. Baseline factors and their association with TBO were analyzed using multivariable logistical regression. The association between TBO and survival rates was determined by Cox proportional hazards regression analysis. RESULTS: In 136 patients, 84 (62%) achieved a TBO when complications were graded as CD ≥2. Greatest negative impact on TBO was the complication rate, lymph node yield, and length of stay. Patients more likely to achieve a TBO were younger, with an increased body mass index and absence of underlying respiratory disease. A nonsignificant trend toward improved OS was seen when TBO was achieved. CONCLUSION: Our TBO rate compares favorably with published data from high-volume centers. Assessment of a unit's TBO may provide a stronger evaluation of quality when assessing where complex surgery should be performed within Australia.

Patients undergoing lymphadenectomy for stage III melanomas of known or unknown primary site do not differ in outcome.

The outcome of patients with palpable melanoma metastases in lymph nodes in the presence (metastatic melanoma of known primary site, MKP) or absence (metastatic melanoma of unknown primary site, MUP) of an identifiable primary tumour remains controversial. Some of the previous studies contained large case series that included historical patients. We aimed to compare outcomes of those with MUPs versus MKPs with palpable lymph node invasion, after staging with modern imaging technology. Aprospective study of patients from a single tertiary institution who were undergoing lymph node dissection for palpable metastatic melanoma between 2000 and 2011 was conducted. All patients were ascertained by computerised tomography scanning and most diagnosed after 2004 had positron emission tomography scanning also. Clinicopathological details about the primary melanoma and lymph node dissections were gathered. Factors associated with recurrence and melanoma-specific mortality in those with MKP and with MUP were assessed using univariate and multivariate analyses. Out of 485 patients studied, 82 had MUP and 403 had MKP. Patients were followed up for a median of 17.4 and 19.0 months, for MKP and MUP, respectively. Five-year adjusted melanoma-specific survival was 58% for MUPs versus 49% for MKPs and was not significantly different between the two groups (adjusted Cox proportional Hazard ratio = 0.88 95% confidence interval [0.58, 1.33] p = 0.54). Previously established prognostic factors such as number of positive nodes and extracapsular extension were confirmed in both sets of patients. We conclude that among melanoma patients presenting with clinically detectable nodes, when accurately staged, those without an identifiable primary lesion have similar outcomes to patients with MKP.

Textbook outcomes for oesophagectomy: A valid composite measure assessment tool for surgical performance in a specialist unit.

INTRODUCTION: In 2017 the Dutch Upper Gastrointestinal Cancer Audit Group proposed a ten-item composite measure for a 'textbook outcome' (TBO) following oesophago-gastric resection. Studies have shown associations between TBO and improved conditional and overall survival. The aim of this study was to evaluate the use of TBO to assess the outcomes from a single specialist unit in a country, with low incidence of disease, allowing comparisons with international specialist centres. MATERIALS AND METHODS: Retrospective analysis of prospectively collected oesophageal cancer surgery data at a single centre, in Australia, between 2013 and 2018. Multivariable logistical regression assessed association between baseline factors and TBO. Post-operative complications were analysed in two separate groups as Clavien-Dindo ≥2 (CD ≥ 2) and Clavien-Dindo ≥3 (CD ≥ 3). Cox-proportional hazards regression analysis determined the association between TBO and survival. RESULTS: 246 patients were analysed, with 50.8% (n = 125) achieving a TBO when complications were defined as CD ≥ 2 and 58.9% (n = 145) when using CD ≥ 3. Patients aged ≥75, and those with a pre-operative respiratory co-morbidity were less likely to achieve a TBO. Overall survival was not influenced by TBO when complications were defined as CD ≥ 2, however it was higher when a TBO was achieved, and complications were defined as CD ≥ 3 (HR 0.54, 95% CI, 0.35 to 0.84, P = 0.007). CONCLUSION: TBO is a multi-parameter metric that allowed benchmarking of the quality of oesophageal cancer surgery in our unit, providing favourable outcomes compared with other published data. There was an association between TBO and improved overall survival when the definition of severe complications was CD ≥ 3.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). CONCLUSION: Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

A brief relaxation intervention reduces stress and improves surgical wound healing response: a randomised trial.

Psychological stress has been shown to impair wound healing, but experimental research in surgical patients is lacking. This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients. This randomised controlled trial was conducted at a surgical centre. Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy; exclusion criteria were cancellation of surgery, medical complications, and refusal of consent. Seventy five patients were randomised and 15 patients were excluded; 60 patients completed the study (15 male, 45 female). Participants were randomised to receive standard care or standard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery. In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing. Change in perceived stress from before surgery to 7-day follow-up was assessed using questionnaires. Intervention group patients showed a reduction in perceived stress compared with the control group, controlling for age. Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients (difference in means 0.35, 95% CI 0.66-0.03; t(43)=2.23, p=0.03). Changes in perceived stress were not associated with hydroxyproline deposition. A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients. The intervention may have particular clinical application for those at risk of poor healing following surgery.

Defining cure for esophageal cancer: analysis of actual 5-year survivors following esophagectomy.

BACKGROUND: Esophagectomy is the mainstay of curative treatment for localized esophageal cancer. However, what constitutes cure is not well defined. This study was undertaken to characterize actual 5-year survivors following esophagectomy and to determine prognostic factors for disease-specific survival (DSS) from 60 months. MATERIALS AND METHODS: Between 1987 and 2004, 398 consecutive patients underwent esophagectomy and had potential for 5 years follow-up. Clinicopathological factors associated with DSS from 5 years onward were analyzed. RESULTS: Median DSS was 25 months. Neoadjuvant therapy was administered to 159 of 398 (40%). There were 114 of 398 (29%) actual 5-year survivors. On multivariate analysis, 5-year survivors were significantly more likely to have lower T classification, N classification, and R0 resections compared with patients who died less than 5 years after surgery. There were 66 of 398 patients (17%) with positive margins, and 6 of these were 5-year survivors. Of the 114 5-year survivors, 17 (15%) subsequently died of esophageal cancer. Prognostic factors for DSS after surviving 5 years were age and T classification for patients treated with neoadjuvant therapy and surgery alone, respectively. Powerful prognostic factors from time of treatment, including nodal status, were no longer prognostic factors after surviving to 5 years. CONCLUSIONS: No single clinicopathological variable negated survival to 5 years. Prognostication once surviving 5 years is difficult. The majority of 5-year survivors can be considered cured of esophageal cancer.

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.

Risk stratification for early esophageal adenocarcinoma: analysis of lymphatic spread and prognostic factors.

BACKGROUND: Knowledge of factors related to outcome is vital for the selection of therapeutic alternatives for patients with early (T1) esophageal adenocarcinoma. This study was undertaken to determine predictors of lymphatic spread and prognostic factors for T1 esophageal adenocarcinoma following esophagectomy. MATERIALS AND METHODS: A prospectively maintained database identified 85 patients with T1 esophageal adenocarcinoma who underwent esophagectomy without neoadjuvant therapy. Depth of tumor invasion (T stage) was subdivided into mucosal (T1a) or submucosal invasion (T1b). Median follow-up was 59 months. RESULTS: Thoracoscopically assisted 3-phase esophagectomy was performed in 73 of 85 patients (86%). Lymph node metastases (N stage) were identified in 9 of 85 patients (11%). Depth of tumor invasion (T stage), lymphovascular invasion (LVI), and poor differentiation were associated with N stage. The patients could be stratified into 4 risk groups for lymph node metastases: group I--T1a (0 of 35 patients [0%] with positive nodes); group II--T1b, well/moderate differentiation and no LVI (1 of 28 patients [4%] with positive nodes); group III--T1b, poor differentiation and no LVI (2 of 9 patients [22%] with positive nodes); and group IV--T1b any grade with LVI (6 of 13 patients [46%] with positive nodes). Survival analyses found T stage, N stage, LVI, and poor differentiation to be significant prognostic factors. CONCLUSIONS: Risk stratification is possible for patents with T1 esophageal adenocarcinoma. Local resection techniques without lymphadenectomy may be alternatives for T1a tumors. Esophagectomy should remain the standard of care for patients with T1b tumors and those with LVI or poor differentiation considered for neoadjuvant therapy.

Isolated limb infusion for malignant melanoma: predictors of response and outcome.

PURPOSE: Isolated limb infusion (ILI) is an alternative to isolated limb perfusion (ILP) for the treatment of unresectable limb melanoma recurrence. The aims of this study were to determine the response rates of unresectable local and/or in-transit melanoma of the upper or lower limb to ILI and to identify factors predictive of survival. METHODOLOGY: A prospective database identified 74 patients (35 male and 39 female) with local and/or in-transit melanoma recurrence without metastatic disease who underwent hyperthermic ILI with melphalan at a single institution between January 1996 and December 2008. Three patients could not be evaluated for response. Median follow-up was 34 months. RESULTS: Of the 74 patients, the majority had N2c disease (57/74, 67%), while 17/74 (33%) patients had N3 disease. Median maximum temperature achieved was 38.1 degrees C and median tourniquet time was 32.5 min. Wieberdink III/IV complications occurred following 7/74 (10%) ILI and were associated with higher limb volumes and higher total melphalan dose. Complete response (CR) was seen following 17/71 (24%) ILI and the partial response rate was 30% (22/71). The median duration of CR was 43 months. Univariable analyses found that limb volume >8.0 l and maximum limb temperature >38.5 degrees C were the only independent factors predictive for a CR following ILI. Multivariate analyses identified CR and positive lymph nodes as the only independent prognostic factors for melanoma-specific survival. CONCLUSIONS: Patients who obtain CR have significantly improved survival compared with nonresponders. The challenge remains to improve CR rates and prospectively identify responders.