A systematic review and meta-analysis of mediastinoscopy-assisted transhiatal esophagectomy (MATHE).

BACKGROUND: Transhiatal esophagectomy (THE) avoids thoracotomy but sacrifices mediastinal lymphadenectomy. Mediastinoscopy-assisted transhiatal esophagectomy (MATHE) allows for visualisation and en-bloc dissection of mediastinal lymph nodes while retaining the benefits of THE. However, given its novel inception, there is a paucity of literature. This study aimed to conduct the first meta-analysis to explore the efficacy of MATHE and clarify its role in the future of esophagectomy. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to May 1, 2023. Studies were included if they reported outcomes for patients with esophageal cancer who underwent MATHE. Meta-analyses of proportions and pooled means were performed for the outcomes of intraoperative blood loss, lymph node (LN) harvest, mean hospital length of stay (LOS), mean operative time, R0 resection, conversion rates, 30-day mortality rate, 5-year OS, and surgical complications (anastomotic leak, cardiovascular [CVS] and pulmonary complications, chyle leak and recurrent laryngeal nerve palsy [RLN]). Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 223 articles; 28 studies and 1128 patients were included in our analysis. Meta-analyses of proportions yielded proportion rates: 30-day mortality (0 %, 95 %CI 0-0), 5-year OS (60.5 %, 95 %CI 47.6-72.7), R0 resection (100 %, 95 %CI 99.3-100), conversion rate (0.1 %, 95 %CI 0-1.2). Among surgical complications, RLN palsy (14.6 %, 95 %CI 9.5-20.4) were most observed, followed by pulmonary complications (11.3 %, 95 %CI 7-16.2), anastomotic leak (9.7 %, 95 %CI 6.8-12.8), CVS complications (2.3 %, 95 %CI 0.9-4.1) and chyle leak (0.02 %, 95 %CI 0-0.8). Meta-analysis of pooled means yielded means: LN harvest (18.6, 95 %CI 14.3-22.9), intraoperative blood loss (247.1 ml, 95 %CI 173.6-320.6), hospital LOS (18.1 days, 95 %CI 14.4-21.8), and operative time (301.5 min, 95 %CI 238.4-364.6). There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. CONCLUSION: MATHE is associated with encouraging post-operative mortality and complication rates, while allowing for radical mediastinal lymphadenectomy with reasonable lymph node harvest.

Effects of Hyperthermia and Hyperthermic Intraperitoneal Chemoperfusion on the Peritoneal and Tumor Immune Contexture.

Hyperthermia combined with intraperitoneal (IP) drug delivery is increasingly used in the treatment of peritoneal metastases (PM). Hyperthermia enhances tumor perfusion and increases drug penetration after IP delivery. The peritoneum is increasingly recognized as an immune-privileged organ with its own distinct immune microenvironment. Here, we review the immune landscape of the healthy peritoneal cavity and immune contexture of peritoneal metastases. Next, we review the potential benefits and unwanted tumor-promoting effects of hyperthermia and the associated heat shock response on the tumor immune microenvironment. We highlight the potential modulating effect of hyperthermia on the biomechanical properties of tumor tissue and the consequences for immune cell infiltration. Data from translational and clinical studies are reviewed. We conclude that (mild) hyperthermia and HIPEC have the potential to enhance antitumor immunity, but detailed further studies are required to distinguish beneficial from tumor-promoting effects.

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis.

The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity.

Resistance to systemic immune checkpoint inhibition in the peritoneal niche.

Immune checkpoint inhibition (ICI) is an established therapeutic option for patients with deficient mismatch repair or high levels of microsatellite instability tumors. Yet, response to ICI among this group is varied, with nearly one-third of patients exhibiting primary resistance. Initial efforts in studying mechanisms of resistance to ICI have focused on intrinsic tumor factors. Host factors such as metastatic niches have unique biological properties that may mediate resistance to ICI but have been less studied date. Patients with metastatic d-MMR/MSI-H gastrointestinal cancers and peritoneal metastases (PM) who had concurrent ascites have been recently shown to have worse outcomes with ICI therapy compared with patients with PM without ascites and patients with non-PM metastases. The juxtaposition of tumors with an intrinsic sensitivity to ICI failing to respond by virtue of the presence of ascites within the peritoneum, brings to the forefront the critical role of the metastatic niche. In this commentary, we discuss mechanisms for ICI resistance that may arise from the immunoprivileged state of the peritoneal cavity, paracrine factors within malignant ascites or tumor-peritoneum interactions. An improved understanding of the peritoneal microenvironment and the use of peritoneal-directed therapies may ameliorate the modest benefit of ICIs in this unique clinical entity.

Lymphocyte-White Cell Ratio Is a Novel Marker of Morbidity Following Colorectal Cancer Surgery.

BACKGROUND: A preoperative marker for morbidity in patients with colorectal cancer would help to risk stratify patients and allow for timely intervention to avert poor outcomes. We conducted this study to evaluate preoperative lymphocyte-white blood cell ratio (LWR) as a marker of postoperative morbidity. METHODS: A prospective cohort of patients who underwent elective surgery for colorectal cancer was reviewed. Three morbidity-related outcomes were described-overall morbidity, multiple morbidities, and severe morbidity, defined as Clavien-Dindo Class ≥3. Univariable and multivariable analyses of presurgical predictors of these three outcomes were performed. Preoperative variables included hemoglobin levels, neoadjuvant therapy, albumin levels, white blood cell count, lymphocyte count, LWR, neutrophil-lymphocyte ratio, and prognostic nutritional index. RESULTS: Of 177 patients, 31.6% (56/177) suffered at least one morbidity, 15.3% (27/177) had multiple morbidities, 7.9% (14/177) suffered severe morbidity. On multivariate analysis, only LWR <0.180 (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.15-5.55) and neoadjuvant therapy (OR 2.49, 95% CI 1.16-5.24) were associated with overall morbidity. For multiple morbidities and severe morbidity, only LWR <0.180 was significantly associated on multivariate analysis with an OR of 2.92 (95% CI 1.19-7.13) and 4.62 (95% CI 1.45-14.73), respectively. CONCLUSIONS: LWR is a preoperative marker which can be conveniently applied using standard preoperative blood tests. LWR is an independent risk factor for overall morbidity, multiple morbidities, as well as severe morbidity when used with a cut-off of LWR<1.80.

Age is an independent risk factor for increased morbidity in elective colorectal cancer surgery despite an ERAS protocol.

INTRODUCTION: Elderly patients with colorectal cancer are high-risk surgical candidates. ERAS protocols have been developed to mitigate against these risks. We performed this study to quantify the risks which elderly patients face and then to determine independent risk factors for short-term ERAS-specific outcomes. METHODS: An analysis of a prospectively collected audit database of all patients who underwent elective colorectal cancer resection within an ERAS framework from January 2018 to December 2018 was performed. Elderly was defined in our study as age ≥ 65 years. RESULTS: There were 172 elective colorectal cancer resections performed. Ninety-seven (56.4%) were elderly. Elderly patients were at increased risk of developing post-operative complications (33.0% vs 16.0%, p = 0.011), longer time to diet (3.4 vs 2.2 days, p = 0.001), and longer hospital stay (10.9 vs 6.7 days, p = 0.007). Independent risk factors were determined for the abovementioned three outcomes. Elderly status was the only risk factor for increased complications (OR 2.61 95% CI (1.05-6.51), p = 0.040). For delayed time to soft diet, male gender (OR 6.67(1.92-20.0), p = 0.002), open approach (OR 9.06(2.26-36.30), p = 0.002), and increased operative time (OR 1.01(1.00-1.01) p = 0.014) were risk factors. Finally, elderly age (OR 5.53(1.82-16.84), p = 0.003), leucocyte count (OR 1.39(0.76-2.57), p = 0.038), open approach (OR 5.26(1.41-19.62), p = 0.013), operative time (OR 1.01(1.00-1.01), p = 0.021), and Clavien-Dindo classification (OR 7.97(1.27-49.88), p = 0.027) were risk factors for prolonged length of stay. CONCLUSION: Elderly patients are intrinsically at risk for increased complications, longer time to soft diet and longer hospital stay. ERAS protocols may need to be specifically tailored for elderly patients.

Recent Advances in Intra-peritoneal Chemotherapy for Gastric Cancer.

Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.

Patient-Reported Outcomes and Long-Term Results of a Randomized Controlled Trial Comparing Single-Port Versus Conventional Laparoscopic Inguinal Hernia Repair.

BACKGROUND: Surgical techniques for inguinal hernia repair have evolved rapidly from open methods to conventional laparoscopic totally extra-peritoneal (CTEP) and recently single-port TEP (STEP). As there is currently no randomized controlled trial (RCT) reporting long-term patient-reported outcomes between CTEP and STEP, we reviewed patients who were randomized to CTEP or STEP 5 years after surgery. METHODS: Telephone interviews were administered to patients with primary unilateral inguinal hernia recruited for the RCT comparing CTEP and STEP in 2011. The modified Body Image Questionnaire was used to measure long-term patient-reported outcomes. RESULTS: Forty-two out of forty-nine of the STEP group and forty-one out of fifty of the CTEP group responded to phone interviews. Median follow-up time, demographic data and clinical outcomes were comparable between both groups. The Body Image Score (5-20: 5-least dissatisfied, 20-most dissatisfied; BIS score ± SD, STEP vs. CTEP, 5.33 ± 0.90 vs. 7.17 ± 1.87, p < 0.001) and Cosmetic Score (2-20: 2-least satisfied, 20-most satisfied; CS score ± SD, STEP vs. CTEP, 19.05 ± 1.31 vs. 15.87 ± 1.57, p < 0.001) were superior in the STEP group. Similarly, self-reported scar perception (1-cannot be seen, 2-can barely be seen, 3-visible; scar perception score ± SD, STEP vs. CTEP, 1.29 ± 0.51 vs. 2.55 ± 0.64, p < 0.001) and overall experience score (1-least satisfied, 10-most satisfied; overall satisfaction score ± SD, STEP vs. CTEP, 9.57 ± 0.67 vs. 8.22 ± 0.94, p < 0.001) were superior in the STEP group. CONCLUSION: Patients who underwent STEP reported superior cosmetic and satisfaction scores and comparable surgical outcomes 5 years after surgery compared to the CTEP group. STEP should be strongly considered in patients who are concerned about long-term cosmetic outcomes and should be offered if surgical expertise is available. Trial registration NCT02302937.

Kamikawa Double-Flap Reconstruction After Minimally Invasive Ivor-Lewis Esophagectomy.

Despite the high incidence of reflux esophagitis, there are few reports of antireflux modifications for minimally invasive Ivor-Lewis esophagectomy. We present the case of a 63-year-old man with mid-thoracic esophageal squamous cell carcinoma who underwent minimally invasive Ivor-Lewis esophagectomy after neoadjuvant chemoradiotherapy. Laparoscopic dissection, gastric tube creation, and mobilization was performed. Thoracoscopic esophageal dissection, subcarinal, paraesophageal and diaphragmatic lymphadenectomy were performed, followed by esophagogastric anastomosis with double seromuscular flap reconstruction to recreate the lower esophageal sphincter. The operation was completed in 618 minutes with 200 mL blood loss and the patient recovered uneventfully. A morphologic sphincter was seen on postoperative contrast study.

Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours.

BACKGROUND: Women with unilateral breast cancer have an increased risk of developing bilateral breast cancer (BBC). Patients with metachronous BBC (mBBC) usually have an earlier age of onset, and their prognoses have been shown to be either similar or poorer than those with synchronous BBC (sBBC). Given the differing presentation and characteristics of breast cancers in the Asian population and the West, this study aims to characterize Asian patients with BBC. METHODS: All patients who had oncological breast surgery between 2001 and 2010 at the Singapore General Hospital and National Cancer Centre Singapore were reviewed. Patients with BBC were identified and studied. RESULTS: A total of 5520 Singaporean women had oncological breast surgery, 155 women (2.8%) had BBC. Of those with BBC, 47.1% (n = 73) were synchronous and 52.9% (n = 82) metachronous (mean interval of 39.4 months), and there was no difference in median age in both groups (54 years of age). Patients with sBBC were more likely to have a positive family history and had asymptomatic contralateral tumours. Although patients with sBBCs were more likely to have ER/PR positive and Her2 negative tumours, they had a lower 5-year overall survival than those with mBBC (P = 0.022). CONCLUSION: Our study shows that Asian women with BBC have different characteristics to their Western counterparts. In particular, women with sBBC tended to have a lower 5-year overall survival compared to those with mBBC, despite having seemingly biologically favourable tumours, which suggest that there may be more underlying their tumour biology and genetics.

Correction to: Prevalence of colorectal cancer in acute uncomplicated diverticulitis and the role of the interval colonoscopy.

The original version of this article, unfortunately, contained errors. The first and family names of the authors were interchanged. The correct author names are now correctly presented in this article. The original article has been corrected.].

Prevalence of colorectal cancer in acute uncomplicated diverticulitis and the role of the interval colonoscopy.

PURPOSE: Although computed tomography (CT) is the imaging modality of choice for diagnosing colonic diverticulitis today, there remains a risk of colorectal cancer mimicking diverticulitis due to overlapping imaging features. Current practice guidelines recommend interval colonoscopy after diverticulitis to exclude occult malignancy. Some authors have suggested that this may be unnecessary in patients with uncomplicated diverticulitis. The aim of our study was to examine the prevalence of occult colorectal cancer in patients with CT-proven acute uncomplicated diverticulitis in an Asian population. METHODS: This was a retrospective study of all patients admitted for CT-proven acute uncomplicated diverticulitis between 2007 and 2011 in a single institution. Colonoscopy and histopathology reports were reviewed for patients who underwent interval colonic evaluation. For patients who defaulted follow-up, national health records were reviewed for any subsequent diagnoses of colorectal cancer. The primary outcome was prevalence of colorectal cancer in the cohort. Secondary outcome was prevalence of advanced adenomas. RESULTS: A total of 227 patients with acute uncomplicated diverticulitis were included in our study. One hundred and thirty-five patients (59.5%) underwent follow-up colonic evaluation. The overall prevalence of colorectal cancer was 1.8%, with half these patients presenting with acute colonic obstruction after defaulting follow-up evaluation. Of the patients, 1.5% who underwent colonoscopy had advanced adenomas. CONCLUSION: Prevalence of colorectal cancer in patients with CT-proven acute uncomplicated diverticulitis may not be as low as previously suggested. We recommend that patients with acute uncomplicated diverticulitis continue to be offered interval colonoscopy until larger studies demonstrate the safety of omission.