Quality of Life Following the Surgical Management of Gastric Cancer Using Patient-Reported Outcomes: A Systematic Review.

Introduction: Surgical management of gastric adenocarcinoma can have a drastic impact on a patient's quality of life (QoL). There is high variability among surgeons' preferences for the type of resection and reconstructive method. Peri-operative and cancer-specific outcomes remain equivalent between the different approaches. Therefore, postoperative quality of life can be viewed as a deciding factor for the surgical approach. The goal of this study was to interrogate patient QoL using patient-reported outcomes (PROs) following gastrectomy for gastric cancer. Methods: This systematic review was registered at Prospero and followed PRISMA guidelines. Medline, Embase, and Scopus were used to perform a literature search on 18 January 2020. A set of selection criteria and the data extraction sheet were predefined. Covidence (Melbourne, Australia) software was used; two reviewers (P.C.V. and E.J.) independently reviewed the articles, and a third resolved conflicts (A.B.F.). Results: The search yielded 1446 studies; 308 articles underwent full-text review. Ultimately, 28 studies were included for qualitative analysis, including 4630 patients. Significant heterogeneity existed between the studies. Geography was predominately East Asian (22/28 articles). While all aspects of quality of life were found to be affected by a gastrectomy, most functional or symptom-specific measures reached baseline by 6-12 months. The most significant ongoing symptoms were reflux, diarrhoea, and nausea/vomiting. Discussion: Generally, patients who undergo a gastrectomy return to baseline QoL by one year, regardless of the type of surgery or reconstruction. A subtotal distal gastrectomy is preferred when proper oncologic margins can be obtained. Additionally, no one form of reconstruction following gastrectomy is statistically preferred over another. However, for subtotal distal gastrectomy, there was a trend toward Roux-en-Y reconstruction as superior to abating reflux.

Survival of Patients With Head and Neck Merkel Cell Cancer: Findings From the Pan-Canadian Merkel Cell Cancer Collaborative.

Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Due to its relatively low incidence and limited prospective trials, current recommendations are guided by historical single-institution retrospective studies. Objective: To evaluate the overall survival (OS) of patients in Canada with head and neck MCC (HNMCC) according to American Joint Committee on Cancer 8th edition staging and treatment modalities. Design, Setting, and Participants: A retrospective cohort study of 400 patients with a diagnosis of HNMCC between July 1, 2000, and June 31, 2018, was conducted using the Pan-Canadian Merkel Cell Cancer Collaborative, a multicenter national registry of patients with MCC. Statistical analyses were performed from January to December 2022. Main Outcomes and Measures: The primary outcome was 5-year OS. Multivariable analysis using a Cox proportional hazards regression model was performed to identify factors associated with survival. Results: Between 2000 and 2018, 400 patients (234 men [58.5%]; mean [SD] age at diagnosis, 78.4 [10.5] years) with malignant neoplasms found in the face, scalp, neck, ear, eyelid, or lip received a diagnosis of HNMCC. At diagnosis, 188 patients (47.0%) had stage I disease. The most common treatment overall was surgery followed by radiotherapy (161 [40.3%]), although radiotherapy alone was most common for stage IV disease (15 of 23 [52.2%]). Five-year OS was 49.8% (95% CI, 40.7%-58.2%), 39.8% (95% CI, 26.2%-53.1%), 36.2% (95% CI, 25.2%-47.4%), and 18.5% (95% CI, 3.9%-41.5%) for stage I, II, III, and IV disease, respectively, and was highest among patients treated with surgery and radiotherapy (49.9% [95% CI, 39.9%-59.1%]). On multivariable analysis, patients treated with surgery and radiotherapy had greater OS compared with those treated with surgery alone (hazard ratio [HR], 0.76 [95% CI, 0.46-1.25]); however, this was not statistically significant. In comparison, patients who received no treatment had significantly worse OS (HR, 1.93 [95% CI, 1.26-2.96)]. Conclusions and Relevance: In this cohort study of the largest Canada-wide evaluation of HNMCC survival outcomes, stage and treatment modality were associated with survival. Multimodal treatment was associated with greater OS across all disease stages.

Higher Rate of Lymphedema with Inguinal versus Axillary Complete Lymph Node Dissection for Melanoma: A Potential Target for Immediate Lymphatic Reconstruction?

BACKGROUND: The present study was conducted to define the lymphedema rate at our institution in patients undergoing axillary (ALND) or inguinal (ILND) lymph node dissection (LND) for melanoma. It aimed to examine risk factors predisposing patients to a higher rate of lymphedema, highlighting which patients could be targeted for immediate lymphatic reconstruction (ILR). METHODS: A retrospective chart review was conducted between October 2015 and July 2020 to identify patients who had undergone ALND or ILND for melanoma. The main outcome measures were rates of transient and permanent lymphedema. Univariate and multivariate analyses were performed to assess the relationship between lymphedema rate and factors related to patient characteristics, surgical procedure, pathology findings, and adjuvant treatment. RESULTS: Between October 2015 and July 2020, 66 patients underwent LND for melanoma: 34 patients underwent ALND and 32 patients underwent ILND. At a median follow-up of 29 months, 85.3% (n = 29) of patients having had an ALND did not experience lymphedema, versus 50.0% (n = 16) of ILND (p = 0.0019). The rates of permanent lymphedema for patients having undergone ALND and ILND were 11.8% (n = 4) and 37.5% (n = 12) respectively (p = 0.016, NS). The rate of transient lymphedema was 2.9% (n = 1) for ALND and 12.5% (n = 4) for ILND (p = 0.13, NS). On univariate analysis, the location of LND and wound infection were found to be significant factors for lymphedema. On multivariate analysis, only the location of LND remained a significant predictor, with the inguinal location predisposing to lymphedema. CONCLUSION: This study highlights the high rate of lymphedema following ILND for melanoma and is a potential target for future patients to be considered for ILR.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

BACKGROUND: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population. METHODS: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada. Univariable and multivariable logistic regression analyses were performed to identify predictors of SLNB positivity. RESULTS: Overall, 676 patients were analyzed. Most patients had one or more high-risk features: Breslow thickness 0.8-1 mm in 78.1% of patients, ulceration in 8.3%, mitotic rate > 1/mm2 in 42.5%, Clark's level ≥ 4 in 34.3%, lymphovascular invasion in 1.4%, nodular histology in 2.9%, and absence of tumor-infiltrating lymphocytes in 14.4%. Fifty-three patients (7.8%) had a positive SLNB. Breslow thickness and mitotic rate independently predicted SLNB positivity. The odds of positive SLNB increased by 50% for each 0.1 mm increase in thickness past 0.7 mm (95% confidence interval [CI] 1.05-2.13) and by 22% for each mitosis per mm2 (95% CI 1.06-1.41). Patients who had one excised node (vs. two or more) were three times less likely to have a positive SLNB (3.6% vs. 9.6%; odds ratio 2.9 [1.3-7.7]). CONCLUSIONS: Our international multi-institutional data confirm that Breslow thickness and mitotic rate independently predict SLNB positivity in patients with T1 melanoma. Even within this highly selected population, the number needed to diagnose is 13:1 (7.8%), indicating that more work is required to identify additional predictors of sentinel node positivity.

Immediate Lymphatic Reconstruction during Axillary Node Dissection for Breast Cancer: A Systematic Review and Meta-analysis.

The objective of this study is to summarize the current body of evidence detailing the impact of immediate lymphatic reconstruction (ILR) on the incidence of breast cancer-related lymphedema (BCRL) following axillary node dissection (ALND). Methods: Medline and Embase databases were queried for publications, where ILR was performed at the time of ALND for breast cancer. Exclusion criteria included lymphaticovenous anastomosis for established BCRL, animal studies, non-breast cancer patient population studies, and descriptive studies detailing surgical technique. Meta-analysis was performed with a forest plot generated using a Mantel -Haenszel statistical method, with a random-effect analysis model. Effect measure was reported as risk ratios with associated 95% confidence intervals. The risk of bias within studies was assessed by the Cochrane Collaboration tool. Results: This systematic review yielded data from 11 studies and 417 breast cancer patients who underwent ILR surgery at the time of ALND. There were 24 of 417 (5.7%) patients who developed BCRL following ILR. Meta-analysis revealed that in the ILR group, 6 of 90 patients (6.7%) developed lymphedema, whereas in the control group, 17 of 50 patients (34%) developed lymphedema. Patients in the ILR group had a risk ratio of 0.22 (CI, 0.09 -0.52) of lymphedema with a number needed to treat of four. Conclusions: There is a clear signal indicating the benefit of ILR in preventing BCRL. Randomized control trials are underway to validate these findings. ILR may prove to be a beneficial intervention for improving the quality of life of breast cancer survivors.

Associations Between the Density of Oil and Gas Infrastructure and the Incidence, Stage and Outcomes of Solid Tumours: A Population-Based Geographic Analysis.

BACKGROUND: We hypothesized that there are geographic areas of increased cancer incidence in Alberta, and that these are associated with high densities of oil and gas(O+G) infrastructure. Our objective was to describe the relationship between O+G infrastructure and incidence of solid tumours on a population level. METHODS: We analyzed all patients >=18 years old with urological, breast, upper GI, colorectal, head and neck, hepatobiliary, lung, melanoma, and prostate cancers identified from the Alberta Cancer Registry from 2004-2016. Locations of active and orphan O+G sites were obtained from the Alberta Energy Regulator and Orphan Well Association. Orphan sites have no entity responsible for their maintenance. ArcGIS (ESRI, Toronto, Ontario) was used to calculate the distribution of O+G sites in each census distribution area (DA). Patient residence at diagnosis was defined by postal code. Incidence of cancer per DA was calculated and standardized. Negative binomial regression was done on O+G site density as a categorical variable with cutoffs of 1 and 30 wells/100km2, compared to areas with 0 sites. RESULTS: 125,316 patients were identified in the study timeframe;58,243 (46.5%) were female, mean age 65.6 years. Breast (22%) and prostate (19.8%) cancers were most common. Mortality was 36.5% after a median of 30 months follow up (IQR 8.4 - 68.4). For categorical density of active O+G sites, RR was 1.02 for 1-30 sites/100km2 (95% CI=0.95-1.11) and 1.15 for >30 sites/100km2 (p<0.0001, 95%CI=1.11-1.2). For orphan sites, 1-30 sites RR was 1.25 (p<0.0001, 95%CI=1.16-1.36) and 1.01 (p=0.97, 95%CI=0.7-1.45) for >30 sites. For all O+G sites, RR for 1-30 sites was 1.03 (p=0.4328, 95%CI=0.95-1.11) and 1.15 (p<0.0001, 95%CI=1.11-1.2) for >30 sites. CONCLUSION: We report a statistically significant correlation between O+G infrastructure density and solid tumour incidence in Alberta. To our knowledge this is the first population-level study to observe that active and orphan O+G sites are associated with increased risk of solid tumours. This finding may inform policy on remediation and cancer prevention.

Gastric cancer management in elderly patients: a population-based study of treatment patterns and outcomes in gastric cancer patients ≥ 75 years from Alberta, Canada.

BACKGROUND: As Canada's population ages, incidence of gastric cancer in elderly patients is increasing. There is little data on treatment and outcomes of gastric cancer in patients older than age 75. This study aimed to assess treatment patterns and outcomes of non-metastatic elderly gastric cancer patients in Alberta, Canada. METHODS: Records of elderly patients (age 75 or older) diagnosed with localized gastric or gastroesophageal junction cancer between 2007 and 2012 who received curative intent surgery were retrospectively collected from the Alberta Cancer Registry. A chart review was completed to gather demographics; treatment details of surgery, chemotherapy, and radiotherapy; and outcomes. Descriptive analyses were undertaken, and variables were compared with parametric and nonparametric tests where appropriate. RESULTS: 130 predominantly male (69%) patients, median age 80 (range 75-96) were included. 17 patients (13%) received multimodality therapy. 115 (88.5%) had negative margins on final pathology. Mean lymph nodes retrieved were 16 (range 0-43). 46 surgical patients (35.4%) had grade II or higher complications. 13 patients had a perioperative death (Clavien grade V). Four (3.1%) patients completed perioperative chemotherapy, and 13 (10%) patients had adjuvant chemo/radiotherapy. 50 (38.5%) recurred at median 13 months, while 80 (61.5%) did not have a recurrence of their cancer at any time during follow up. The 5 year DFS for the surgery only group was 67.3% and multimodality group was 52.9% (p = 0.25). The 5 year OS for the surgery only group was 38.9% and multimodality group was 47.1% (p = 0.52). CONCLUSIONS: Our findings suggest that even with surgery alone, selected elderly patients with non-metastatic gastric cancer can obtain apparent prolonged survival, despite not receiving standard of care multimodality therapy. More studies are needed to optimise elderly patients' treatment selection.

Evaluation of repeat cytoreductive surgery and heated intraperitoneal chemotherapy for patients with recurrent peritoneal carcinomatosis from appendiceal and colorectal cancers: a multicentre Canadian study

Background: Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin. Methods: Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery. Results: Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III­IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months. Conclusion: Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.

Contexte: Les récurrences péritonéales après une chirurgie cytoréductrice (CCR) et une chimiothérapie hyperthermique intrapéritonéale (CHIP) pour les cancers de l'appendice et colorectaux sont fréquentes. Cette étude visait à évaluer l'innocuité, la faisabilité technique et les résultats périopératoires et à long terme d'une reprise de CCR/CHIP chez les patients qui présentent une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice. Méthodes: Des données ont été recueillies sur des patients traités entre 2000 et 2016 pour une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice par CCR/CHIP dans 2 centres spécialisés. On a tenu compte des données démographiques, des détails des interventions, ainsi que de la morbidité et de la survie. Des analyses ont permis de comparer les premières et deuxièmes CCR/CHIP pour évaluer l'innocuité et l'efficacité des chirurgies répétées. Résultats: De tous les patients soumis à des CCR/CHIP dans les 2 centres, 37 ont subi l'intervention de nouveau. Le temps opératoire a été similaire pour les premières et les deuxièmes chirurgies (412,1 c. 412,5 min, p = 0,74), mais les patients présentaient un score de carcinomatose péritonéale beaucoup plus bas lors de la deuxième chirurgie (21,8 pour la première intervention c. 9,53 pour la seconde, p < 0,001) et des pertes sanguines significativement moindres (1762 mL pour la première intervention c. 790 mL pour la seconde, p = 0,001). On a noté une diminution non significative des complications de grades III­IV et on n'a déploré aucune mortalité à 30 jours en lien avec la reprise de l'intervention. Pour les patients atteints d'un cancer colorectal, la survie médiane sans maladie a été de 9,6 mois et la survie médiane globale a été de 40 mois. Pour les patients atteints d'un cancer de l'appendice, la survie médiane sans maladie a été de 15 mois et la survie médiane globale a été de 64,4 mois. Conclusion: La reprise des CCR/CHIP pour les récurrences de carcinomatose péritonéale ayant leur origine au niveau colorectal ou de l'appendice est sécuritaire chez les patients soigneusement sélectionnés, sans accroissement de la morbidité ou de la mortalité, et elles sont associées à une survie à long terme significative, particulièrement chez les patients ayant un cancer de l'appendice. Ces résultats appuient la reprise des CCR/CHIP chez ces patients.

Surgical management of truncal and extremities atypical lipomatous tumors/well-differentiated liposarcoma: A systematic review of the literature.

INTRODUCTION: Atypical lipomatous tumors or well-differentiated liposarcomas (ALT/WDLS) are low-grade soft tissue tumors that are commonly located on the trunk and extremities. There is no consensus on the best surgical approach for ALT/WDLS. METHODS: A systematic literature review of PubMed, Medline, Embase, Scopus, and google scholar was performed. All published studies on trunk or extremities ALT/WDLS with reported outcome data were considered and independently screened for inclusion by at least two of the authors. RESULTS: A total of eighteen studies comprising 793 patients with ALT/WDLS were included. 580 patients underwent marginal excision, with local recurrence observed in 69 (11.9%). 213 patients underwent wide excision with local recurrence in 7(3.3%). Recurrent tumors were successfully re-resected with marginal or wide excision. Dedifferentiation was confirmed in 9 patients (1.1%), and a distant pulmonary metastasis in 1 patient (0.1%). DISCUSSION: Marginal excision of truncal or extremities ALT/WDLS results in a slightly higher local recurrence rate. However, recurrences are almost always amenable to re-resection. The findings support the use of marginal excision for truncal or extremities ALT/WDLS.

Accuracy of clinical, laboratory, and computed tomography findings for identifying hollow viscus injury in blunt trauma patients with unexplained intraperitoneal free fluid without solid organ injury.

BACKGROUND: We sought to define the accuracy of findings for detecting hollow viscus injury (HVI) in patients with blunt abdominal trauma (BAT) and unexplained intra-peritoneal free fluid without solid organ injury (UIPFFWSOI). METHODS: We screened all consecutive hemodynamically stable patients presenting to a quaternary-care trauma-centre who had an abdominal computed tomography (CT) scan for BAT and UIPFFWSOI (January 2007-December 2014). RESULTS: Of 3796 patients identified during the study period, 39 presented with UIPFFWSOI. Fifteen underwent therapeutic laparotomy. Seatbelt sign (+LR approaches infinity), diffuse peritonitis (+LR approaches infinity), number of CT cuts with fluid (c-statistic = 0.65), and a lower arterial pH at presentation (c-statistic = 0.62) were most predictive of HVI. Patients operated on within 24 h had shorter stays than those operated on later (median 9 vs. 14 days, p = 0.03). CONCLUSIONS: Our findings suggest that clinical examination and measurements of intraperitoneal fluid volume may help identify HVIs in BAT patients.

Chitosan film containing poly(D,L-lactic-co-glycolic acid) nanoparticles: a platform for localized dual-drug release.

PURPOSE: To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release. METHODS: Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS). RESULTS: Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days. CONCLUSIONS: The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.