A Prospective Study Evaluating the Feasibility and Accuracy of Post-operative Laryngeal Ultrasonography (LUSG) in Assessment of Vocal Cord Function After Esophagectomy.

BACKGROUND: Vocal cord paresis (VCP) is a serious complication after esophagectomy. Conventional diagnosis of VCP relies on flexible laryngoscopy (FL), which is invasive. Laryngeal ultrasonography (LUSG) is non-invasive and convenient. It has provided accurate VC evaluation after thyroidectomy but it is unclear if it is just as accurate following esophagectomy. This prospective study evaluated the feasibility and accuracy of LUSG in VC assessment on day-1 after esophagectomy. METHODS: Consecutive patients from a tertiary teaching hospital who underwent elective esophagectomy were prospectively recruited. All received pre-operative FL, and post-operative LUSG and FL on Day-1, each performed by a blinded, independent assessor. The primary outcomes were feasibility and accuracy of LUSG in the diagnosis of VCP on Day-1 post-esophagectomy. The accuracy of voice assessment (VA) was analyzed. RESULTS: Twenty-six patients were eligible for analysis. The median age was 70 years (66-73). Majority were male (84.6%). Twenty-five (96.2%) received three-phase esophagectomy. Twenty-four (96%) had same-stage anastomosis at the neck. Three (11.5%) developed temporary and one (3.8%) developed permanent unilateral VCP. Overall VC visualization rate by LUSG was 100%; sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of LUSG were 75.0%, 100%, 100%, 98.0%, 98.1% respectively, and superior to VA. Combining LUSG with VA findings could pick up all VCPs i.e. improved sensitivity and NPV to 100%. CONCLUSION: LUSG is a highly feasible, accurate and non-invasive method to evaluate VC function early after esophagectomy. Post-operative FL may be avoided in patients with both normal LUSG and voice.

Clonal relationship and alcohol consumption-associated mutational signature in synchronous hypopharyngeal tumours and oesophageal squamous cell carcinoma.

BACKGROUND: The patients with dual oesophageal squamous cell carcinoma (ESCC) and hypopharyngeal cancer (HPC) have poor prognosis; their underlying genetic pathogenesis is unclear. We hypothesise that development of synchronous ESCC/HPC depends on multicentricity or independent origin, rather than multifocality due to local or lateral spreading. METHOD: Multiple region whole-exome sequencing (M-WES) and clonality analysis were used to assess clonal relationship and spatial inter- or intra-tumour heterogeneity (ITH) in 62 tumour regions from eight dual ESCC/HPC and ten ESCC patients. RESULTS: All synchronous ESCC/HPC patients had COSMIC 16 mutation signatures, compared to only 40% ESCC in the current study (p = 0.013) and public data set (n = 165, p = 0.003). This alcohol consumption-related mutation signature 16, commonly involved in multiple alcohol-related cancers, was significantly associated with drinking and alcohol metabolism-related ADH1B rs1229984. The mutational landscape and copy number profiles were completely distinct between the two primary tumours; clonality analysis further suggested the two primary tumours shared no or only one clone accompanying independent subclone evolution. M-WES strategy demonstrated higher sensitivity and accuracy for detection of mutational prevalence and the late branch mutations among different regions in the ESCC tumours, compared to traditional sequencing analysis based on single biopsy strategy. Patients with high ITH assessed by cancer cell fraction analysis after M-WES were significantly associated with both relapse and survival. CONCLUSIONS: Our hypothesis-generating M-WES ITH assessment data have implications for prognostication. Collectively, our findings support multicentric independent clonal evolution, the field cancerisation theory, and suggest novel insights implicating an aetiologic role of alcohol metabolism in dual ESCC/HPC carcinogenesis.

Impact of Extracapsular Extension of Lymph Node in Adenocarcinoma of the Stomach.

BACKGROUND: Extracapsular extension (ECE) of lymph node may have important prognostic impact for patients with adenocarcinoma of the stomach, but it generally is ignored in staging systems and prognostic models. This study aimed to examine the impact that ECE of lymph node has on prognosis for patients with adenocarcinoma of the stomach. METHODS: The study analyzed 321 consecutive patients with gastric cancer who underwent radical gastrectomy between January 2008 and December 2015. None of these patients had distant metastases. Lymph node metastases were found in 187 patients. The ECE grade was evaluated according to the previously described system used in head and neck cancers. Deposits of cancer cells in sub-serosal fat without a recognizable lymph node were classified as ECE grade 4. Survival outcomes were compared using Kaplan-Meier and Cox regression analyses. A nomogram was constructed using identified significant prognostic factors. The predictive accuracy and model performance were measured by the concordance index (C-index). RESULTS: Patients with ECE(+) showed significantly worse 3-year overall survival (OS) and disease-free survival (DFS) than those without ECE. In the sensitivity analysis, ECE had independent prognostic value for both 3-year OS and 3-year DFS, whereas ECE grading showed little impact on mortality trend or disease progression trend. The ECE-based nomogram showed a significantly higher C-index than the pathological tumor and node staging (pTN) staging system. CONCLUSIONS: The adverse prognostic impact of ECE was validated. Sub-serosal tumor deposits without recognizable lymph node tissue are recommended for inclusion in the ECE definition. A nomogram involving ECE could provide better individual prediction of survival for patients with lymph node-positive gastric cancer.

Nuclear Localization of DNAJB6 Is Associated With Survival of Patients With Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells.

BACKGROUND & AIMS: The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulates chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates ß-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients who underwent esophagectomy with no preoperative chemoradiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1 ± 2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs, or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. RESULTS: In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2 ± 1.8 months; 95% confidence interval [CI], 15.6-22.8 mo) than patients whose tumors had low nuclear levels of DNAJB6 (12.6 ± 1.4 mo; 95% CI, 9.8-15.4 mo; P = .004, log-rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than patients with low levels (hazard ratio, 0.562; 95% CI, 0.379-0.834; P = .004). Based on log-rank analysis and Cox regression analysis, the combination of the nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or bad outcomes (P < .0005 for both analyses). There was a negative association between the nuclear level of DNAJB6 and the presence of lymph node metastases (P = .022; Pearson χ(2) test). Cancer cell lines that overexpressed DNAJB6a formed tumors more slowly in nude mice than control cells or cells that expressed a mutant form of DNAJB6a that did not localize to the nucleus. DNAJB6 knockdown in cancer cell lines promoted their growth as xenograft tumors in mice. A motif of histidine, proline, and aspartic acid in the J domain of DNAJB6a was required for its tumor-suppressive effects and signaling via AKT1. Loss of DNAJB6a resulted in up-regulation of AKT signaling in cancer cell lines and immortalized esophageal epithelial cells. Expression of a constitutively active form of AKT1 restored proliferation to tumor cells that overexpressed DNAJB6a, and DNAJB6a formed a complex with AKT1 in living cells. The expression of DNAJB6a reduced the sensitivity of ESCC to AKT inhibitors; the expression level of DNAJB6a affected AKT signaling in multiple cancer cell lines. CONCLUSIONS: Nuclear localization of DNAJB6 is associated with longer survival times of patients with ESCC. DNAJB6a reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their proliferation and growth of xenograft tumors in mice. DNAJB6a might be developed as a biomarker for progression of ESCC.

Multigene Profiling of Circulating Tumor Cells in Esophageal Squamous Cell Carcinoma Identifies Prognostic Cancer Driver Genes Associated with Epithelial-Mesenchymal-Transition Progression and Chemoresistance.

We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprising CCND1, ECT2, EpCAM, FSCN1, KRT5, KRT18, MET, TFRC, TWIST1, and VEGFC, was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples (n = 77) and clinicopathological features in ESCC patients (n = 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size (p = 0.031). The CTC-high patients were significantly correlated with advanced cancer stages (p = 0.013) and distant metastasis (p = 0.029). High mRNA levels of TWIST1 (Hazard Ratio (HR) = 5.44, p = 0.007), VEGFC (HR = 6.67, p < 0.001), TFRC (HR = 2.63, p = 0.034), and EpCAM (HR = 2.53, p = 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed that TWIST1 facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through the TWIST1-TGFBI-ZEB1 axis in ESCC, highlighting the prognostic and therapeutic potential of TWIST1 in clinical ESCC treatment.

Circulating Tumor Cell Enumeration for Serial Monitoring of Treatment Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma.

We aim to reveal the clinical significance and potential usefulness of dynamic monitoring of CTCs to track therapeutic responses and improve survival for advanced ESCC patients. Peripheral blood (PB) (n = 389) and azygos vein blood (AVB) (n = 13) samplings were recruited prospectively from 88 ESCC patients undergoing curative surgery from 2017 to 2022. Longitudinal CTC enumeration was performed with epithelial (EpCAM/pan-cytokeratins/MUC1) and mesenchymal (vimentin) markers at 12 serial timepoints at any of the pre-treatment, all of the post-treatments/pre-surgery, post-surgery follow-ups for 3-year, and relapse. Longitudinal real-time CTC analysis in PB and AVB suggests more CTCs are released early at pre-surgery and 3-month post-surgery into the circulation from the CTRT group compared to the up-front surgery group. High CTC levels at pre-treatments, 1-/3-month post-surgery, unfavorable changes of CTC levels between all post-treatment/pre-surgery and 1-month or 3-month post-surgery (Hazard Ratio (HR) = 6.662, p < 0.001), were independent prognosticators for curative treatment. The unfavorable pre-surgery CTC status was independent prognostic and predictive for neoadjuvant treatment efficacy (HR = 3.652, p = 0.035). The aggressive CTC clusters were more frequently observed in AVB compared to PB. Its role as an independent prognosticator with relapse was first reported in ESCC (HR = 2.539, p = 0.068). CTC clusters and longitudinal CTC monitoring provide useful prognostic information and potential predictive biomarkers to help guide clinicians in improving disease management.

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma.

Importance: Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease. Objective: To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival. Design, Setting, and Participants: This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes. Intervention: Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT). Main Outcomes and Measures: Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS). Results: A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10-6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre-cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10-4). Conclusions and Relevance: The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

The role of 18F-fluorodeoxyglucose positron emission tomography in thyroid neoplasms.

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has established itself as an important imaging modality in many oncological and nononcological specialties and, as a consequence, it is increasingly being used in clinical practice. Since the first report of FDG being taken up by metastatic differentiated thyroid carcinoma (DTC) cells >20 years ago, various groups of investigators have explored the potential role of FDG-PET scanning in patients with benign and malignant thyroid neoplasms. With the increasing demand for FDG-PET scanning, clinicians are faced with the challenge of managing an increasing number of FDG-PET-detected thyroid incidentalomas because their significance remains unclear. The aims of this review are to address some of these issues, specifically, the clinical significance of FDG-PET-detected thyroid incidentalomas, the ability of FDG-PET to characterize thyroid nodules, especially those with indeterminate fine needle aspiration cytology results, and the role of FDG-PET in patients with confirmed primary DTC and with suspected recurrent DTC, by reviewing the current literature.

Spigelian hernia: Our total extraperitoneal approach and a systematic review of the literature.

INTRODUCTION: Spigelian hernia is a rare lateral ventral hernia traditionally repaired through open incision with extensive dissection. Three laparoscopic techniques have been reported in the literature: intraperitoneal onlay mesh (IPOM), transabdominal preperitoneal (TAPP), and total extraperitoneal (TEP). TEP is less popular than the other approaches. We evaluated TEP's safety and effectiveness and compared different laparoscopic techniques. METHODS: All patients with Spigelian hernia who had undergone extended TEP (eTEP) repair with mesh in our center from January 2007 to February 2020 were studied. A three-port technique with a preperitoneal space created by telescope at the midline was adopted. A systematic review on laparoscopic mesh repair was performed by searching for "Spigelian hernia" and "laparoscopic" from 1999 to 2019 in the MEDLINE database. RESULTS: Seven patients underwent eTEP repair for Spigelian hernia. Five presented with abdominal mass and underwent preoperative imaging. Two were diagnosed incidentally during TEP for inguinal hernia. The mean operative duration was 65 minutes (range, 40-93 minutes). There were no open conversions or intraoperative complications. The mean length of hospital stay was 1.4 days (range, 1-3 days). The mean follow-up period was 44.3 months. One patient developed seroma. There was no recurrence or chronic pain. We identified 197 laparoscopic mesh repairs reported in 41 articles. IPOM (n = 91) was the most popular approach, followed by TAPP (n = 70) and TEP (n = 36). Laparoscopic mesh repair of Spigelian hernia is safe and offers excellent outcomes. CONCLUSION: We found the eTEP approach safe and effective for Spigelian hernia repair. IPOM, TAPP, and TEP are comparable.

Laparoscopic Total Extraperitoneal Groin Hernia Repair in Females: Comparison of Outcomes Between Preservation or Division of the Uterine Round Ligament.

Background: Laparoscopic repair has been recommended as the method-of-choice of groin hernia repair among women. Whether the round ligament of uterus should be divided to facilitate mesh placement remains controversial. This study aims to review the outcomes of laparoscopic total extraperitoneal (TEP) groin hernia repair in women and to evaluate the impact of division of round ligament. Methods: Consecutive female patients with inguinal or femoral hernias who underwent elective laparoscopic TEP repair at a single institution from 2006 to 2017 were included for retrospective analysis. Primary outcomes were postoperative pain, genital prolapse, and recurrence. Outcomes of patients who had the round ligament divided were further compared with those with round ligament preserved and multivariable adjusted analysis was performed. Results: Sixty-eight patients with a total of 77 TEP repairs were included in the 12-year study period. The mean age was 45 ± 16 years old. Incidental femoral hernia was identified in 4 patients (5.9%). There was 1 (1.3%) recurrence upon mean follow-up of 42.9 ± 37.3 months. The round ligament was divided in 67.5% of patients, and upon multivariable adjusted analysis, there were no statistically significant differences in outcomes in terms of chronic pain (odds ratio [OR] = 2.210, P = .357), paresthesia (OR = 0.241, P = .149), and genital prolapse (OR = 0.327, P = .415) when compared with patients with preserved round ligament. Conclusion: Laparoscopic groin hernia repair in women is associated with low recurrence. Division of round ligament intraoperatively facilitates mesh placement and has minimal impact on clinical outcomes.

Tension-free mesh repair of inguinal hernia in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is the first-line renal replacement therapy for end-stage renal failure patients in Hong Kong. Abdominal wall hernia is a common mechanical complication of PD, and early surgical repair has been advocated to reduce complications. This study aims to review the outcomes of tension-free mesh repair of inguinal hernia in PD patients. METHODS: All PD patients who underwent elective repair of inguinal hernia from 2009 to 2015 were identified from a single centre for retrospective analysis. Primary outcomes included surgical complications, perioperative dialysis technique and recurrence. RESULTS: Twenty-one patients with a total of 26 inguinal hernia repairs were included in this 7-year retrospective study. All were males, and the mean age was 68 ± 10 years. Diabetic nephropathy (n = 9, 42.9%) and glomerulonephritis (n = 7, 33.3%) were the two most common causes of renal failure. All hernias were detected after the initiation of PD, and the mean duration of PD to hernia detection was 16 months (range 1-65 months). Lichtenstein open mesh repair was performed in all patients. Complications included seroma (n = 3, 11.5%) and ischaemic orchitis (n = 1, 3.8%). There were no mesh infection or recurrence. Twenty patients (95.2%) received intermittent peritoneal dialysis post-operatively and returned to continuous ambulatory PD in 15 to 30 days. Only one patient (4.8%) required bridging haemodialysis due to Tenckhoff catheter blockage. CONCLUSIONS: Tension-free mesh repair is associated with low morbidity and low recurrence rates in PD patients. Timely management and close collaboration with renal physicians are essential to continue PD after repair.

A Randomized Controlled Trial Comparing Short-term Outcomes of Self-Gripping (Progrip) Mesh Versus Fibrin Sealant in Laparoscopic Total Extraperitoneal Hernioplasty.

BACKGROUND: There are no data comparing the use of self-gripping mesh with standard mesh in total extraperitoneal repair (TEP). In this prospective study we aim to study the incidence of chronic pain between Progrip (PG) and standard mesh fixed by fibrin sealant (FS). MATERIALS AND METHODS: Under Institutional Review Board approval, from April 2016 to May 2017, patients with primary unilateral or bilateral inguinal hernia eligible for TEP were recruited. Before mesh insertion they were randomized into PG or FS (Tisseel). Demographics, intraoperative, and postoperative data were recorded. Patients were followed up for at least 1 year. Visual Analog Scale was used to record pain scores. Primary outcome was the incidence of chronic pain at 3 months after surgery. RESULTS: One hundred fifty patients were randomized. Of the 150 patients (193 hernias), 76 were randomized to PG and 74 randomized to FS. Demographic data such as age, presence of comorbidities, smoking history, mean body mass index was comparable in both groups. Bilateral hernias occurred in 25 (32.9%) and 18 (24.3%) patients in PG and FS group, respectively. Mean mesh deployment time was 283.7 seconds (range, 140 to 720 s) in PG group and 301.9 seconds (range, 67 to 1006 s) in FS group (P=0.30). A total of 5 patients were lost at follow-up and they were excluded from subsequent data analysis. Seroma occurred in 15 (20.3%) and 16 (22.5%) patients in PG and FS group, respectively (P=0.45). Mean Visual Analog Scale at 2 weeks (cough) was highest at 1.05 and 1.02 in PG and FS group, respectively (P=0.62). Eight (12.3%) and 15 (23.4%) patients in PG and FG group, respectively, reported pain at 3-month follow-up (P=0.1). Of those who experienced pain, majority was mild pain which did not affect activities of daily living. At a mean follow-up of 13.1±5.4 months, no recurrence was detected. CONCLUSIONS: There was no significant difference in terms of chronic pain between PG and FS group. The use of PG is effective in TEP.

Comparison of laparoscopic versus open gastrectomy for gastric cancer.

BACKGROUND: This study aimed to compare the short-term and long-term outcomes of laparoscopic gastrectomy (LG) and open gastrectomy (OG) for gastric cancer in a tertiary referral center in Hong Kong. METHODS: Two hundred and ninety-four consecutive patients with gastric cancer who underwent radical gastrectomy with curative intent between January 2008 and December 2015 were analyzed. Data was prospectively collected and reviewed. Propensity score matching was applied at a ratio of 1:1 to compare the OG and LG groups. RESULTS: After propensity score matching, operation duration (294.7 vs 231.8min, P < 0.01) was significantly longer while estimated blood loss (191.6 vs 351.0 ml, P = 0.01) was significantly less in LG group compared with OG. There were no significant differences in postoperative complications and mortality between LG and OG groups (postoperative complication rate, 35.2% vs 40.7%, P = 0.69; 90-day mortality rate, 1.9% vs 3.7%, P = 1.00). Three-year OS and 3-yr DFS of patients who underwent LG was not inferior to that of patients who had OG (P = 0.34; P = 0.51). However, there were significantly more peritoneal recurrences among the OG group than LG group (P < 0.01). CONCLUSIONS: LG has comparable outcomes for gastric cancer, even in advanced tumors. We could appropriately increase the proportion of laparoscopic gastrectomy for gastric cancer.

Real-world Scenario: CROSS Regimen as Preoperative Therapy for Oesophageal Squamous Cell Carcinoma.

BACKGROUND: Preoperative chemoradiation (CROSS regimen) has been widely adopted worldwide. The survival advantage imparted is especially impressive for oesophageal squamous cell carcinoma (OSCC). This study aimed at investigating the efficacy of the CROSS regimen in real-world scenario. METHODS: This is a retrospective study of all patients with OSCC intended for preoperative treatment using the CROSS regimen during 2012-2017. Patients were divided into two groups: those within the selection criteria in the CROSS trial and those beyond criteria, namely age > 75 years old, tumour length > 8 cm or clinical M1 stage of lymph node involvement (AJCC 6th edition). Clinical outcome and survival data were compared. RESULTS: Eighty-eight patients were included. There were 46 patients in the "CROSS eligible" group and 42 in the "CROSS ineligible" group. By intention-to-treat, the estimated median survival was 24.2 months vs. 12.7 months, respectively (p = 0.047). The results were much inferior compared to that published in the original CROSS trial. Univariable and multivariable analyses showed tumour length and resectability as independent variables affecting survival. DISCUSSION: In a real-world scenario, the clinical outcome remains suboptimal and the excellent results in the trial setting were not reproducible in this Asian cohort. Patient selection is one key element accountable for the difference. The efficacy of the CROSS regimen may not be adequate for patients with more advanced disease. The optimal multimodal therapy for this group of patients remains undefined.

Surgical margins in breast conservation therapy: how much should we excise?

BACKGROUND: Breast conservation therapy (BCT) has become the standard of treatment for early stage breast cancer, and the surgical margin was one of the important factors that affected risk of local recurrence. This review looks at the safe margin for BCT in early stage invasive breast cancer and ductal carcinoma in situ (DCIS). METHODS: Published literature abstracted in Medline was searched using the gateway site from the US National Library of Medicine. CONCLUSIONS: A positive margin is associated with increased risk of local recurrence after BCT for invasive breast cancer and DCIS. However there was no cut off for the margin width and the significance of a close margin remains controversial. It was generally accepted that the risk of local recurrence was low if the margin was >or=10 mm while margins that were <2 mm were considered inadequate. The surgeon needs to balance the risk between local recurrence and cosmesis in planning BCT so that the prognosis is not compromised.

Laparoscopic versus open repair for small paraumbilical hernia: A retrospective review.

INTRODUCTION: The advantages of laparoscopic surgery for ventral hernia repairs are well documented, but its application for small paraumbilical hernias has been less studied. There is no consensus regarding the best technique. METHODS: All patients who had open (suture or mesh) and laparoscopic repair of primary paraumbilical hernia between September 2007 and September 2017 in a single center were identified. Hernial defects of 2 cm or less were included; recurrent hernias were excluded. Primary outcomes included operative time, length of hospital stay, and surgical complications. RESULTS: Seventy-seven patients were recruited: 54 (70.1%) had open repair and 23 (29.9%) had laparoscopic repair. Forty-six patients (85%) in the open group had primary suture repair. The mean operative time was significantly shorter in the open group than in the laparoscopic group (27.2 vs 56.1 min, P < 0.05). The length of hospital stay in the open group was significantly shorter than in the laparoscopic group (0.8 vs 1.4 days, P = 0.00). Early complications rates were similar, with wound complications in 5.6% (3/54) of open repair patients and 4.3% (1/23) of laparoscopic repair patients (P = 1.0). Among open repair patients, 19 patients (35.2%) were successfully discharged within 12 h after operation. Two patients (3.7%) in the open simple suture group developed recurrence, but no recurrence was identified in the laparoscopic group; this was not statistically significant (P = 1.0). CONCLUSION: The laparoscopic approach is comparable to the open approach in the repair of small paraumbilical hernias. For small paraumbilical hernias, we recommend that laparoscopic repair be reserved for obese patients or those with suspected multiple hernial defects.

Elective laparoscopic totally extraperitoneal repair for Spigelian hernia: A case series of four patients.

INTRODUCTION: Spigelian hernia (SH) is uncommon. Clinical diagnosis may be difficult, but computed tomography (CT) can help to establish the diagnosis. Laparoscopic repair is increasingly performed because it is associated with low morbidity rates. Laparoscopic approaches include transabdominal preperitoneal (TAPP), intraperitoneal onlay mesh (IPOM), and totally extraperitoneal (TEP). Here, we report our experiences of TEP repair for SH. METHODS: A retrospective review was performed on all patients with SH who underwent elective laparoscopic TEP repair from 2007 to 2017 at Tung Wah Hospital, Hong Kong. RESULTS: Four patients with SH were identified in the study period: three with a preoperative diagnosis of SH confirmed by CT scan and one diagnosed incidentally during TEP repair for inguinal hernia. The patients' mean age was 66.8 years (range, 55.0-82.0 years). The mean BMI was 22.8 kg/m2 (range, 20.8-23.6 kg/m2 ). The mean size of the SH defect was 2.0 cm (range, 0.5-3.0 cm). The mean operative time was 59 min (range, 40-86 min). Concomitant direct inguinal hernia was found in one patient and repaired simultaneously. All patients were discharged on postoperative day 1. One patient developed seroma, which subsided on conservative management. At a mean follow-up of 36 months (range, 2-108 months), there was no recurrence. CONCLUSION: Laparoscopic repair for SH is preferred over the open approach as it is associated with a low morbidity rate and a short hospital stay. In our experience, TEP technique is safe and effective in laparoscopic SH repair.

Serum microRNA-193b as a promising biomarker for prediction of chemoradiation sensitivity in esophageal squamous cell carcinoma patients.

Esophageal squamous cell carcinoma (ESCC) is the most predominantly occurring type of esophageal cancer worldwide. Locally advanced ESCC patients are treated by neoadjuvant chemoradiation for tumor downstaging prior to tumor resection. Patients receiving this treatment have an increased expectation of cure via the following tumor resection and have better survival outcomes. However, not all patients respond well to chemoradiation and poor responders suffer from treatment-associated toxicity and complications without benefits. No method is currently available to predict patient chemoradiation response and to exclude poor responders from ineffective treatment. To address this clinical limitation, the present study aimed to identify non-invasive biomarkers for predicting patient chemoradiation response. Due to the features of microRNA (miRNA) in cancer diagnosis, prognosis and treatment response prediction, serum miRNA arrays were performed to identify potential miRNA(s) that may be used for chemoradiation response prediction in ESCC. Using an miRNA array to compare pre-treatment serum sample pools from 10 good responders and 10 poor responders, the present study identified miR-193b, miR-942 and miR-629* as candidate miRNAs for predicting chemoradiation response. Subsequent validation using reverse transcription-quantitative polymerase chain reaction confirmed that miR-193b, however not miR-942 and miR-629*, were significantly increased in sera from 24 good responders, compared with 23 poor responders. Further analyses using the receiver operating characteristic curve revealed a strong predictive power of serum miR-193b on discriminating good responders from poor responders to chemoradiation. In addition, a high serum level of miR-193b was significantly associated with better survival outcomes. Therefore, serum miR-193b may be considered a promising biomarker for predicting chemoradiation response and post-therapy survival of ESCC patients.